PubMed Health⌕ Search

Biomedical subjects

A Solini

Publications and source records attributed to A Solini.

At least 19 recordsLinked to original sources
PubMed2006

High glucose and homocysteine synergistically affect the metalloproteinases-tissue inhibitors of metalloproteinases pattern, but not TGFB expression, in human fibroblasts.

AIMS/HYPOTHESIS: Atherosclerosis is particularly aggressive in patients with diabetes. Hyperhomocysteinaemia causes oxidative stress and cytokine secretion: its atherogenic effect is mediated by an enhanced inflammatory response. Matrix metalloproteinases (MMPs) regulate extracellular matrix degradation and remodelling, and contribute to the vulnerability of the atherosclerotic lesion. Fibroblasts contribute to collagen biosynthesis and participate in plaque remodelling via expression and release of MMP2 and MMP9. To explore the role of hyperhomocysteinaemia in cellular pathways involved in plaque growth and stability in diabetic patients, we studied the effect of hyperhomocysteinaemia in human fibroblasts grown in the presence of normal or high glucose concentrations. MATERIALS AND METHODS: In fibroblasts of five normal subjects, grown at 5.5 or 22 mmol/l glucose and treated with homocysteine, we determined: (1) MMP2, MMP9 and tissue inhibitor of metalloproteinases (TIMP)-1 (an MMP inhibitor) production by western blot analysis; (2) their activity by zymography; (3) TGFB1 expression by real-time PCR; and (4) TGFB, fibronectin and IL6 release by ELISA. RESULTS: Hyperhomocysteinaemia increased the production and enzymatic activity of MMP2 and MMP9, the effect being more pronounced in high glucose. Conversely, TIMP1 production was reduced by hyperhomocysteinaemia in both conditions, especially in high glucose. Hyperhomocysteinaemia also stimulated IL6 release, at least in part through nuclear factor-kappaB activation. TGFB1 expression was not affected by hyperhomocysteinaemia either in normal or in high glucose. CONCLUSIONS/INTERPRETATION: Homocysteine upregulates the MMP-TIMP pathway and IL6 release, the effect being stronger in the presence of high glucose. These actions of homocysteine may contribute to the increased atherogenesis observed in diabetic patients with poor metabolic control.

Drug Synergism↗
PubMed2006

Effect of short-term folic acid supplementation on insulin sensitivity and inflammatory markers in overweight subjects.

OBJECTIVE: Inflammation plays a pivotal role in the atherosclerotic process, and some chemokines seem to be crucial in the pathogenesis of vascular damage. High-serum homocysteine, recently recognized as an independent risk factor for vascular disease might increase cytokine and chemokine levels, thus amplifying endothelial damage; moreover, it might worse insulin resistance, thus further contributing to enhance cardiovascular risk. The effect of folic acid supplementation in improving in vivo endothelial function is still debated. In this study, we investigated the effect of folic acid supplementation on insulin sensitivity and peripheral markers of inflammation in overweight healthy subjects. DESIGN: The study was performed as an unmasked randomized placebo-controlled trial of 12 weeks duration. SUBJECTS: Sixty healthy volunteers with normal glucose tolerance and BMI between 25 and 29 kg/m2 were enrolled. MEASUREMENTS: Biochemical parameters and plasma concentrations of homocysteine and of some inflammatory molecules were measured at baseline and at the end of the study, together with an estimation of insulin sensitivity. RESULTS: Subjects receiving folic acid supplementation showed a decrement of homocysteine and an amelioration of insulin sensitivity; this treatment was also associated with a significant drop in the circulating concentration of monocyte chemoattractant protein-1, interleukin-8 and C-reactive protein, in the absence of any significant variation of BMI or fat mass. CONCLUSIONS: In healthy overweight subjects a short-term folic acid supplementation reduces the circulating level of some inflammatory mediators independently of weight change, thus suggesting a potential therapeutic role for folic acid in the protection from atherogenesis and cardiovascular diseases.

Adult↗
PubMed2006

Acute vascular events and electrolytes variations in elderly patients.

Alterations in electrolyte balance have been claimed to play a role in the pathophysiology of coronary heart disease; however, the relationship between the electrolyte pattern and other clinical variables immediately after an acute vascular event is unclear. The aim of the present study was to test whether electrolyte and microelement changes characterize the acute phase in patients with different degrees of glucose tolerance admitted to the hospital shortly after an acute cardiovascular or cerebrovascular ischemic event. Two hundred consecutive patients with either myocardial infarction or stroke (SP group), stratified by degree of glucose tolerance, were studied within six hours of admission, and compared against 125 patients admitted for conditions other than acute vascular ischemia (CP). Routine laboratory parameters and serum Na, K, Cl, Mg and Ca concentrations were determined in all patients and compared to those recorded within six months before the admission. Relative to CP and independently of confounding factors including glucose tolerance status, the SP group showed significantly higher plasma glucose and insulin concentrations, higher creatinine and a modified serum electrolyte pattern characterized by significantly lower potassium and magnesium levels and by hypercalcemia and hyperphosphatemia. Irrespective of glucose tolerance, the first hours following an acute vascular event are characterized by marked insulin resistance with a consistent shift in the serum electrolyte pattern. This pattern is the physiological consequence of the attendant compensatory hyperinsulinemia. Its significance for the evolution of ischemic damage remains to be established.

Aged↗
PubMed2004

Lipoprotein lipase gene variants and progression of nephropathy in hypercholesterolaemic patients with type 2 diabetes.

OBJECTIVE: Recent prospective studies have identified hyperlipidaemia as an independent determinant of diabetic nephropathy. Lipoprotein lipase (LPL) is a key enzyme in the postprandial processing of triglycerides and VLDL. Among a number of common sequence variants of the LPL, HindIII has been associated with coronary heart disease and, more recently, with microalbuminuria in type 2 diabetes. We evaluated the progression of renal disease in hypercholesterolaemic type 2 diabetic patients in relation to this polymorphism. DESIGN AND SUBJECTS: We followed up for 4 years 65 consecutively enrolled microalbuminuric patients with type 2 diabetes; of whom 28 had hypercholesterolaemia (6.62 +/- 0.9 mmol L(-1), group A) and 37 were normocholesterolaemic (4.68 +/- 0.5 mmol L(-1), group B). MAIN OUTCOME MEASURES: After performing the genetic analyses, albumin excretion rate (AER) and estimated glomerular filtration rate (GFR), calculated by the simplified equation of the MDRD Study Group, were repeated every year. RESULTS: In group A, AER increased more (deltaAER: 11 [38] vs. 4 [18] microg min(-1) per year in group B, P < 0.0001) while GFR declined faster (-3.5 +/- 2.1 vs. -2.0 +/- 1.4 mL min(-1) per year, P < 0.02). Patients homozygous for the allele + of HindIII showed a significantly faster decline of GFR and a higher increase of AER (both P = 0.0001) even after adjustment for cholesterol levels and anthropometric variables. CONCLUSIONS: In hypercholesterolaemic type 2 diabetic patients with microalbuminuria, the renal disease has an accelerated course, particularly in those carrying the H+/H+ genotype of the HindIII polymorphism at the LPL locus.

Aged↗
PubMed2003

Atorvastatin improves metabolic control and endothelial function in type 2 diabetic patients: a placebo-controlled study.

Several pieces of evidence support a role of inflammatory processes in the pathogenesis of atherosclerosis; it is also known that endothelial dysfunction is the initial lesion of the atherosclerotic process. Among other markers of endothelial dysfunction, some adhesion molecules seem to play an interesting role. The aim of the present study was to evaluate the effect of atorvastatin vs placebo on some indexes of leukocytes adhesion in a group of Type 2 diabetic patients. Twenty-five Type 2 diabetic patients free from microangiopathic complications and with LDL-cholesterol lower than 180 mg/dl were randomized to receive either atorvastatin (T2DA) or placebo (T2Dp) for twelve months. BMI, fasting plasma glucose, glycated hemoglobin (HbA1c), albumin excretion rate (AER), lipid profile, and serum concentrations of vascular cell adhesion molecule-1 (VCAM1), E-selectin and cadherin-5 were measured at baseline and at the end of the follow-up. At T0 E-selectin was 16 +/- 6 ng/ml in T2DA and 17 +/- 13 in T2Dp; VCAM1 was 413 +/- 112 ng/ml in T2DA and 411 +/- 112 in T2Dp. At T12 VCAM1 and E-selectin did not vary in T2Dp, while a significant reduction was observed in T2DA (VCAM1 275 +/- 104 ng/ml and E-selectin 8 +/- 3 ng/ml; p < 0.001 and p < 0.01, respectively). T2DA also showed a reduction of total and LDL cholesterol and an improved glycemic control respect to T2Dp. Hypolipidemic therapy was the strongest independent predictor of the cytokines variations along the time. These results confirm the role of statins in modulating endothelial function also in Type 2 diabetes, outlining a therapeutic role of these molecules probably independent from the hypolipidemic effect.

Adult↗
PubMed2003

Effect of metabolic control on homocysteine levels in type 2 diabetic patients: a 3-year follow-up.

OBJECTIVES: Hyperhomocysteinaemia has emerged as a novel risk factor for cardiovascular disease. The determinants of total homocysteine (tHcy) levels in type 2 diabetic patients (D2p) have not been studied in detail. We examined prospectively the effect of different degrees of metabolic control on plasma tHcy in D2p with preserved kidney function. SUBJECTS AND MAIN OUTCOME MEASUREMENTS: Ninety-five D2p were studied. Clinical parameters, fasting plasma glucose, HbA1c, serum lipids, blood urea nitrogen (BUN) and creatinine, vitamin B12 and folate and tHcy were measured at the baseline and after 36 months. The methylentetrahydrofolate reductase (MTHFR) C677T polymorphism was also determined. Subjects were categorized according to deltaHbA1c into group A (+/-1 point), B (>1 point increase) or C (>1 point decrease). RESULTS: Total homocysteine was reduced in subjects whose HbA1c decreased with time, whilst patients showing a worsened metabolic control had an increased tHcy in respect to baseline. A larger response to the improved metabolic control in terms of tHcy reduction was noted in wild type patients versus those homozygous for the mutation. A multivariate analysis revealed MTHFR polymorphism and HbA1c as strong determinants of changes in tHcy with time. CONCLUSIONS: The findings suggest that in D2p tHcy decreases even with modest improvement of glycaemic control; moreover patients homozygous for the MTHFR C677T mutation show the largest changes in tHcy levels with concomitant changing of HbA1c. These results define a further mechanism through which hyperglycaemia might promote cardiovascular damage in diabetic patients.

Aged↗
PubMed2003

Metabolic profile in patients with benign prostate hyperplasia or prostate cancer and normal glucose tolerance.

Familial predisposition together with several environmental factors may be involved in the pathogenesis of common prostate disease such as benign hypertrophy or prostate neoplasm. A higher incidence of both these conditions has been described in some insulin-resistant states such as obesity, but not much information is available on the effect of metabolic profile on gland morphology. The aim of this study was to evaluate the relation between glucose and lipid pattern and prostate diameters in two groups of non-diabetic individuals with benign prostate hypertrophy or cancer. 109 patients were recruited; plasma glucose, lipids and hormonal profile as well as an ultrasonographic evaluation of the gland volume and diameters were determined. Patients with prostate cancer had significantly higher levels of insulin and were more insulin resistant; in contrast, in subjects with prostate hypertrophy, fasting plasma glucose and--to a lesser extent--serum triglycerides emerged as the main determinants of gland volume. These observations may indicate that an improvement of insulin sensitivity and strategies to maintain a strict glucose and lipid control even in non-diabetic subjects are useful objectives in the prevention of prostate diseases.

Aged↗
PubMed2001

Plasma homocysteine, methylenetetrahydrofolate reductase mutation and carotid damage in elderly healthy women.

Plasma homocysteine (Hcy) is an independent vascular risk factor. Its remethylation to methionine is regulated by the activity of the enzyme 5,10-methylene tetrahydrofolate reductase (MTHFR). A C-to-T substitution at nucleotide 677 of the MTHFR gene is frequently associated to hyperhomocysteinemia. In this study, we evaluated the relationship among MTHFR C677T polymorphism, Hcy and some ultrasonographic parameters at the level of carotid arteries in 120 elderly women with normal ECG, normal blood pressure values, total cholesterol <250 mg/dl, normal glucose tolerance, normal albumin excretion rate. In all subjects, we measured Hcy by HPLC, MTHFR mutation by polymerase chain reaction followed by HinfI digestion and intima-media thickness (IMT), peak velocity of the systolic flow (SP(V)), end-diastolic velocity (ED(V)) and resistance and pulsatility indexes of intracranial circulation (RI and PI) by ultrasound imaging. Twenty-eight women were homozygotes for the wild type allele (Ala/Ala), 72 were heterozygotes (Ala/Val) and 20 were homozygotes for the mutation (Val/Val). Groups were comparable for age, blood pressure values and plasma lipid levels. Hcy was higher in Val/Val group; moreover, after adjustment for confounding factors, Val/Val had significantly greater IMT and ED(V) (P<0.001 and P<0.05, respectively). Logistic analysis revealed that Val/Val genotype was the strongest risk factor for IMT (OR 30.8, 95% CI 2.82-335.6). Our results show that, in elderly healthy women, Val/Val homozygosity for C677T mutation in MTHFR gene could identify subjects at risk for asymptomatic carotid atherosclerotic impairment.

Aged↗
PubMed2001

A defect in glycogen synthesis characterizes insulin resistance in hypertensive patients with type 2 diabetes.

A subgroup of patients with type 2 diabetes shows a clustering of abnormalities such as peripheral insulin resistance, hypertension, and microalbuminuria. To evaluate whether these traits reflect intrinsic disorders of cell function rather than in vivo environmental effects, we studied a group of 7 nondiabetic hypertensive subjects with an altered albumin excretion rate (AER) (HyMA+) and 3 groups of patients with type 2 diabetes: 7 with normal blood pressure and normal AER (DH-MA-), 7 with high blood pressure and normal AER (DH+MA-), and 7 with both high blood pressure and altered AER (DH+MA+). Glucose disposal was measured during an hyperinsulinemic clamp (40 mU. m(2)(-1). min(-1)) with primed deuterated [6.6 (2)H(2)] glucose infusion. In the same subjects, a skin biopsy was performed and the following parameters were investigated: glucose transport (as determined by [(3)H]2-deoxyglucose uptake); glycogen synthase activity (as determined by [(14)C] glucose incorporation from UDP-[U-(14)C] glucose into glycogen); glycogen phosphorylase activity (as measured by the incorporation of [U-(14)C]glucose 1-phosphate into glycogen); and total glycogen content. In vivo glucose disposal was significantly reduced in DH+MA- and DH+MA+, with respect to DH-MA-, HyMA+, and controls. Insulin-stimulated glucose transport was similar in the 3 groups of patients with diabetes. A significant reduction of intracellular glycogen content was observed in DH+MA- and DH+MA+ compared with DH-MA- in both basal and insulin-stimulated conditions, probably because of a major impairment of glycogen synthase activity. Glycogen phosphorylase activity did not show differences between the groups. These results suggest that (1) the combination of type 2 diabetes with hypertension and altered AER is associated with impaired insulin sensitivity, and (2) intrinsic, possibly genetic, factors may account for increased peripheral insulin resistance in hypertensive microalbuminuric patients with type 2 diabetes, pointing to the reduction of glycogen synthase activity as a shared common defect.

Albuminuria↗
PubMed2001

ACE genotype and endothelium-dependent vasodilation of conduit arteries and forearm microcirculation in humans.

The ACE gene is a candidate gene for cardiovascular disease. Endothelial dysfunction is considered an intermediate phenotype in the pathogenesis of hypertension and atherosclerosis. We evaluated the role of ACE gene polymorphism in endothelial function of young healthy humans. We assessed ACE genotype (deletion [D]/insertion [I] polymorphism) in 92 young healthy individuals. In 88 of them, endothelium-dependent (flow-mediated) vasodilation and endothelium-independent (nitroglycerin-induced) vasodilation were measured in the common femoral artery and in the brachial (n=84) artery by echo Doppler technique. In 35 subjects, we also applied the forearm perfusion technique to quantify the responses of the forearm vascular bed to 3 increasing doses of 2 endothelium-dependent vasodilators (acetylcholine and bradykinin) and 1 endothelium-independent vasodilator (sodium nitroprusside). The D allele of the ACE gene was associated with a significant blunting (Delta approximately 26%) of endothelium-dependent vasodilation in the femoral artery (P=0.02) but not in the brachial artery (P=0.55) or in the forearm microcirculation (P=0.70 to 0.80). Endothelium-independent vasodilation was unaffected by the ACE genotype. In young healthy humans, the D allele of the ACE gene is associated with selective endothelial dysfunction of the femoral artery. It remains to be determined whether this association discloses a causal role in vascular, particularly peripheral artery, disease.

Acetylcholine↗
PubMed2001

Enlarged approach to the anterior cervical spine.

In this report a new enlarged approach to the anterior cervical spine is presented. A 66-year-old female, having a large C3-C4-C5 chordoma, recurrent after surgery and following radiotherapy, underwent a surgical resection. The approach allows a wide retraction of the nasopharynx, oropharynx and larynx from the midline, only sacrificing the superior laryngeal nerve on one side. Its continuity can be re-established later by adopting the stent in tube technique. The approach we used presents all the risks of infection common in trans-oral approaches. For this reason, closure of the pharynx in two layers must be meticulous and watertight and reinforced by using a myofascial sternocleidomastoid flap, according to the tracheoesophageal fistula closure technique. A correct alignment of the tongue, the pre-plating of the mandible and the correct suture of the vermillion border guarantee excellent cosmetic and functional results.

Aged↗
PubMed2001

Role of diabetes in influencing leptin concentration in elderly overweight patients.

BACKGROUND: Leptin, the product of the ob gene, could have a significant role in the pathogenesis of obesity and non-insulin-dependent diabetes mellitus. However, it is still debated whether different degrees of glucose tolerance may affect plasma leptin concentrations in obese patients. OBJECTIVE: To investigate whether diabetes might influence leptin concentrations in obese patients. METHODS: We evaluated clinical parameters, anthropometric measures, and sex hormones, fasting plasma leptin, glucose and insulin concentrations in 100 elderly obese diabetic patients and 100 obese non-diabetic control individuals matched for age and sex. RESULTS: After adjustment for age and fat mass, plasma leptin concentrations did not differ between diabetic and non-diabetic obese individuals, in both men and women. In all patients leptin was significantly related to body mass index, fat mass and the homeostasis model insulin resistance index; moreover we observed a significant relationship with fasting plasma glucose and age in diabetic obese women, and with blood pressure values and testosterone concentrations in diabetic obese men. Multiple regression analysis revealed age and fasting plasma glucose to be the only independent determinants of fasting plasma leptin in diabetic obese women. CONCLUSIONS: These data suggest that leptin concentrations do not differ between obese diabetic and obese non-diabetic elderly patients. Among correlates of the metabolic syndrome, systolic pressure seems to be related to leptin only in men. In the postmenopausal or andropausal status, sex hormones are related to leptin concentrations only in diabetic men; in diabetic women, however, high glucose seems to be relevant in maintaining the same leptin concentrations as in non-diabetic women with similar degree of obesity.

Age Factors↗
PubMed2000

The relationship of plasma glucose and electrocardiographic parameters in elderly women with different degrees of glucose tolerance.

Plasma glucose has been regarded as a risk factor for macrovascular complications in diabetes, but less is known about its role in the development of cardiac impairment other than coronary heart disease (CHD). The aim of our study was to determine the relationship between basal and post-OGTT (Oral Glucose Tolerance Test) plasma glucose levels and some ECG parameters in a group of elderly women with normal or impaired glucose tolerance (IGT). One-hundred and one women with normal fasting glucose (<6.0 mmol/L) and no familial history or clinical signs of CHD and diabetes underwent an OGTT and a resting ECG. Based on the degree of glucose tolerance, we identified 24 women with a diagnostic OGTT for either IGT or diabetes; the 77 women (age range 52-88 years) with normal glucose tolerance were further divided into two groups according to their post-OGTT area under the curve (AUCG): below and above the median value (32 and 45 women, respectively). Basal plasma glucose and insulin levels, as well as lipid profile and percent of hypertensive patients were similar in the three groups. Mean corrected QT (QTc) was prolonged as a function of progressive worsening of glucose tolerance even after adjustment for possible confounding factors (p=0.03). A similar relationship was apparent when post-OGTT plasma glucose peak (GP) was considered. In a multiple regression analysis, AUCG and GP were the only factors independently related to both QTc and Sokolow index. Our observations suggest that, even in the presence of a normal glucose tolerance, plasma glucose concentrations during an OGTT are associated with peculiar ECG signs potentially combined with an increased risk of sudden death, arrhythmias, or cardiovascular mortality.

Aged↗
PubMed2000

High glucose modulates P2X7 receptor-mediated function in human primary fibroblasts.

AIMS/HYPOTHESIS: Purinergic receptors are a family of newly characterized plasma membrane molecules involved in several and as yet only partially known cellular functions such as vascular reactivity, apoptosis and cytokine secretion. Little is known about the effect extracellular microenvironment has on their function. Fibroblasts share several features with smooth muscle cells and are an important constituent of the atherosclerotic plaque. Our aim was to evaluate the effect of high glucose concentration on ATP-mediated responses in human fibroblasts. METHODS: Fibroblasts were obtained by skin biopsies and grown at two different glucose concentrations. We evaluated receptor expression by RT-PCR and immunoblotting and receptor localization by immunofluorescence. Plasma membrane potential and calcium changes were measured by fluorescent indicators. Apoptosis was determined by ethidium bromide staining and caspase-3 activation. RESULTS: We show that cells grown in a medium with high glucose concentration underwent great ATP-mediated morphological changes, enhanced apoptosis, caspase 3 activation and interleukin-6 release. We identified P2X7 as the main purinergic receptor involved in these responses. Furthermore, high glucose concentration triggered the assembly of P2X7 into ring-like structures located at the periphery of the cells. CONCLUSION/INTERPRETATION: Given that ATP is frequently released into the extracellular milieu upon cell and tissue damage, secretory exocytosis or activation of plasma membrane transporters, we hypothesize that ATP receptors participate in the pathogenesis of vascular complications of diabetes.

Adenosine Triphosphate↗
PubMed1999

Polymorphisms of angiotensin-converting enzyme and angiotensinogen genes in type 2 diabetic sibships in relation to albumin excretion rate.

Familial clustering of altered albumin excretion and nephropathy risk has been described in both type 1 and type 2 diabetes; moreover, an association of micro-macroalbuminuria and diabetic retinopathy has been recently reported in a large number of white families with type 2 diabetes. Conflicting reports, mainly comparing affected with unaffected unrelated subjects, have suggested a possible role of some genotypes of the renin-angiotensin system in conferring nephropathy risk in type 2 diabetes. To examine the role of genetic factors in influencing albuminuria in families, we studied the relation of angiotensin-converting enzymes (ACE) and angiotensinogen (AGN) genotypes with albumin excretion rate in a population of affected siblings of type 2 diabetic probands. We determined ACE insertion/deletion polymorphism and two polymorphisms of the AGN gene (T174M and M235T) in 160 families with at least one affected member. Defining proband as the patient with the longest known duration of diabetes, we compared the allelic distribution in diabetic probands with and without altered albumin excretion and in their siblings. Allelic distribution of these polymorphisms was similar in the two groups of probands, as well as in their siblings. Identity-by-State (IBS) analysis showed a link between AGN locus and arterial hypertension in these siblings, which was independent from the degree of renal involvement. Thus, our findings suggest that in white families with type 2 diabetes, there is no linkage between the degree of albumin excretion and ACE and AGN polymorphisms, whereas the latter is related to arterial hypertension, as previously found in patients without diabetes but with essential hypertension.

Albuminuria↗
PubMed1999

Human primary fibroblasts in vitro express a purinergic P2X7 receptor coupled to ion fluxes, microvesicle formation and IL-6 release.

We have investigated reponses to extracellular ATP in human fibroblasts obtained by skin biopsies. Our data show that these cells express a P2X7 purinergic receptor, as judged by (1) RT-PCR with specific primers, (2) reactivity with a specific anti-P2X7 antiserum, (3) activation by the selective P2X agonist benzoylbenzoylATP and (4) stimulation of transmembrane ion fluxes. Stimulation with benzoylbenzoylATP, and to a lesser extent with ATP, also caused striking morphological changes and increased formation of cytoplasmic microvesicles. These changes were fully reversible upon nucleotide removal. Two known blockers of P2X receptors, oxidised ATP and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, inhibited the morphological changes fully and the ion fluxes partially. The residual rise in intracellular Ca2+ levels and membrane depolarization observed in the presence of the inhibitors were dependent upon activation of a P2Y-type receptor exhibiting a peculiar pharmacological profile, in that CTP was the preferred agonist. ATP stimulation triggered release of the pro-inflammatory cytokine IL-6 in fibroblasts pre-treated with PMA and bacterial endotoxin. These observations reveal a novel pathway for fibroblast activation and for their recruitment in the inflammatory response.

Blotting, Western↗
PubMed1998

Derangements in protein metabolism induced by type I diabetes mellitus.

In poorly controlled diabetics, the whole-body protein flux is increased by 20-30% in comparison to well-controlled type I diabetes (IDDM) and normal subjects. Intensive insulin administration completely reverses these abnormalities. In poorly controlled IDDM, the primary effect of insulin administration is to reduce the increased protein catabolic rate by suppressing the accelerated rate of protein breakdown. Studies in humans have demonstrated that the increased rate of protein synthesis observed in these patients is the consequence of elevated plasma amino acid levels. When IDDM subjects develop renal complications, a protein-restricted diet may be recommended to preserve the remnant kidney function. However, it has been demonstrated that in IDDM patients, metabolic adaptation to protein restriction is incomplete because suppression of endogenous proteolysis is impaired. Since this component of protein metabolism is very sensitive to insulin action, maintaining strict metabolic control during the protein restriction regimen has been suggested. The major studies on the effects of amino acid and insulin on protein metabolism in patients with diabetes mellitus are reviewed.

Amino Acids↗