ABSTRACT
BACKGROUND AND AIMS: The relationships between very high plasma HDLc and subclinical atherosclerosis are still a matter of debate. METHODS AND RESULTS: Twenty subjects with primary hyperalphalipoproteinemia (HAL, with HDLc in the highest 10th percentile and absence of overt secondary causes of this condition), aged 30-65 years, were compared with 20 age and sex-matched controls. Lipid determination, lipoprotein particle distribution (Lipoprint(®)), Cholesterol Efflux Capacity (CEC), plasma adhesion molecule, analyses of CETP, SRB1 and LIPG genes and of different markers of subclinical vascular disease (ankle-brachial index, ABI; carotid intima-media thickness, cIMT; brachial-artery flow mediated dilation, FMD) were performed. Fasting HDLc levels were 40 mg/dl higher in HAL subjects while LDLc concentration was comparable to control group. CETP gene analysis in HAL subjects identified one novel rare Single Nucleotide Polymorphism (SNP, Asp131Asn), possibly damaging, while the common SNP p.Val422Ile was highly prevalent (50% vs. 27.4% in a control population). No rare mutations associated with HAL were found in SR-B1 and LIPG genes. Polyacrylamide gel electrophoresis in HAL subjects disclosed larger and more buoyant HDL particles than in controls, while LDL profile was much more similar. ABI, cIMT and arterial plaques did not differ in cases and controls and the two groups showed comparable FMD at brachial artery examination. Similarly, ABCA1 and ABCG1 HDL-mediated CEC, the most relevant for atheroprotection, did not discriminate between the groups and only ABCG1 pathway seemed somewhat related to arterial reactivity. CONCLUSIONS: HDL dimension, function and genetics seem scarcely related to subclinical atherosclerosis and vascular reactivity in middle-aged HAL subjects.
Subject(s)
Carotid Intima-Media Thickness , Cholesterol Ester Transfer Proteins/deficiency , Cholesterol, HDL/blood , Lipid Metabolism, Inborn Errors/blood , Adult , Aged , Ankle Brachial Index , Brachial Artery/metabolism , Case-Control Studies , Cholesterol Ester Transfer Proteins/blood , Cholesterol Ester Transfer Proteins/genetics , Cholesterol, LDL/blood , Endothelium, Vascular/metabolism , Female , Humans , Intercellular Adhesion Molecule-1/blood , Lipase/genetics , Lipid Metabolism, Inborn Errors/genetics , Logistic Models , Male , Middle Aged , Scavenger Receptors, Class B/genetics , Triglycerides/blood , Vascular Cell Adhesion Molecule-1/bloodABSTRACT
BACKGROUND AND AIMS: Our recent data document that a low glycemic index (LGI) Neapolitan pizza prepared with a mix of Kamut and whole wheat flours plus Glucomannan, (i) has a lower impact on postprandial hyperglycemic spikes than pizza made of whole wheat flour, (ii) is pleasant and appreciated as traditional one and (iii) does not cause any gastro-intestinal troubles. The aim of our study was to describe the validation process underlying the identification of the right mix of those elements for a LGI pizza preventing gastro-intestinal disturbances. METHODS: we described all procedures followed to make good products with different combinations of the three components and a series of tests made by four well-experienced professional pasta-making masters, one nutritionist, five diabetologists, one nurse and twenty volunteers with T1DM. RESULTS: we could identify the best workable and most suitable flour mix to achieve both pleasant taste and low glycemic impact proving to be efficient in real-life twin paper providing results from diabetic patients. CONCLUSIONS: this kind of food will certainly help people with diabetes eat pizza without risking any serious deterioration of their own glucose control while fully enjoying socially active life.
Subject(s)
Diabetes Mellitus/metabolism , Dietary Fiber/analysis , Flour/analysis , Gastrointestinal Tract/metabolism , Glycemic Index , Triticum/chemistry , Blood Glucose/analysis , Diabetes Mellitus/pathology , Flour/adverse effects , Gastrointestinal Tract/pathology , Humans , Postprandial PeriodABSTRACT
Opposed to whole wheat (WWP), traditional pizza (TP) is loved by patients with type 1 diabetes mellitus (T1DM) despite causing hyperglycemia. 50 well-trained T1DM patients had higher glucose levels after TP than after WWP or mixed flour pizza, which however was tasty, digestible and metabolically appropriate to break diet monotony.
Subject(s)
Diabetes Mellitus, Type 1/diet therapy , Glycemic Index , Hypoglycemic Agents/therapeutic use , Insulin Infusion Systems , Insulin/therapeutic use , Taste , Adolescent , Adult , Blood Glucose/analysis , Diabetes Mellitus, Type 1/drug therapy , Dietary Carbohydrates , Dietary Fiber , Female , Humans , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Male , Middle Aged , Treatment Outcome , Young AdultABSTRACT
Diabetes Mellitus (DM) is the most common cause of renal failure and ESRD all over the world, and often requires an individualized insulin treatment regimen. Malnutrition, depression-related eating behavior changes, high on-off-dialysis day-to-day glycemic variability and frequent hypoglycemic events occurring during or immediately after dialysis make it hard to identify best insulin dosage in hemodialyzed patients. This suggests a prudent attitude including non-stringent control, despite which repeated hypoglycemia quite often occurs in such patients. When looking for possible sources of hypoglycemia, health professionals too often overlook the identification of skin lipodystrophy (LD) due to an incorrect insulin injection technique. This mini-review focuses on the high frequency (57%) of LD in a cohort of 1004 insulin-treated people with DM on dialysis consecutively referring to our joint medical centers, and on its relationship with hypoglycemia and glycemic control/variability. When taking on such patients, care team members accept to face a complex disease burdened with several risk factors requiring high professional skills, and have to keep in mind also the possible presence of any LD areas eventually interfering with expected results. A timely educational intervention on the correct injection technique can help reduce the high risk of hypoglycemia and large glycemic variability in dialysed people with DM.
Subject(s)
Insulin/adverse effects , Lipodystrophy/chemically induced , Renal Dialysis/adverse effects , Diabetic Nephropathies/therapy , Humans , Hypoglycemia/chemically induced , Insulin/administration & dosage , Kidney Failure, Chronic/therapyABSTRACT
Erectile dysfunction (ED) is associated with a reduced quality of life; it represents a risk factor for the development of depression. ED may induce depression, loss of self-esteem, poor self-image, anxiety, and tension in the relationship with the partner. These emotional disturbances can create physical conditions that lead to increased difficulty in achieving an erection. Depression can deprive a person of the ability to experience many of life's pleasures. It not only affects the mind but also the body--often in unexpected ways. As a result, many men who have been diagnosed with depression find themselves suffering from another condition: ED. Sexual dysfunction is a big problem also in patients with chronic renal failure and seriously affects their quality of life. About 40% of men on dialysis suffer from ED. Many uremic patients have additional symptoms including reduction of libido and a decreased frequency of sexual intercourse. With the start of dialysis some of these symptoms may improve, without, however, returning to normal.
Subject(s)
Erectile Dysfunction/etiology , Kidney Failure, Chronic/complications , Quality of Life , Humans , MaleABSTRACT
Here, we report the alterations in renal water handling in healthy volunteers during a 6 h thermoneutral water immersion at 34 to 36 degrees C. We found that water immersion is associated with a reversible increase in total urinary AQP2 excretion.
Subject(s)
Aquaporin 2/physiology , Diuresis/physiology , Immersion , Water/physiology , Adult , Aquaporin 2/urine , Arginine Vasopressin/urine , Creatinine/urine , Humans , Male , Osmolar ConcentrationABSTRACT
The ability to act jointly with others is a hallmark of primate evolution and is fundamental for human development. In recent years, the study of coordination strategies between individuals performing joint actions has received growing attention. However, when, in the course of post-natal development, this cognitive-motor function emerges is still unknown. Here, we studied dyads of peers aged 6-9 years, as well as adult subjects, while they performed a task where the same action, namely, exerting hand force on an isometric joystick to move a visual cursor from a central toward a peripheral target, was performed in a "solo" and in a social "cooperative" context. The results revealed that during joint action planning, an attempt to synchronize one's own action with that of a partner emerges at 7 years of age, together with a reduction in the duration and variability of the reaction times. A critical time is 8 years, when "solo" performance reaches a high level of accuracy. From this age, another coordination strategy, based on the online monitoring of the peer's behavior, seems to be implemented during the execution of joint action. The motor and cognitive development occurring during childhood are discussed as possible mechanisms mediating, respectively, the capability and the propensity to take into account the peer's behavior for implementing a common action plan.
Subject(s)
Attention/physiology , Child Development/physiology , Cognition/physiology , Cooperative Behavior , Psychomotor Performance/physiology , Age Factors , Child , Female , Humans , Interpersonal Relations , Male , Motor Activity , Online SystemsABSTRACT
The focus of this research was the development and evaluation of different complex liquid and solid media for the isolation and growth of phytoplasma strains infecting grapevine plants. Previously reported media supporting phytoplasma isolation are commercial and not easy to modify in order to improve performance and selectivity towards obtaining pure cultures of 'Candidatus Phytoplasma' species. Three media (Piv®, CB and MB) were therefore evaluated for phytoplasma isolation and colony formation under microaerophilic growing conditions, using grapevine canes from plants showing yellows symptoms, and infected by "flavescence dorée", "bois noir" and aster yellows phytoplasmas as sources. The newly developed methodology was applied for two years at three sample collection times. Broad applicability and a good repeatability in supporting phytoplasma colony formation were obtained in Pivs® and CBs media. While the MB medium did not support phytoplasma isolation and growth, the CB media support a phytoplasma growth comparable to the one obtained in the previously reported media. This medium has the advantage of a formulation that allow its modification to implement specificity towards selective phytoplasma growth. Moreover preliminary trials on serial dilutions and tetracycline addition confirmed some phytoplasma growth behaviours.
Subject(s)
Bacteriological Techniques , Culture Media/chemistry , Phytoplasma/growth & development , Phytoplasma/isolation & purification , DNA, Bacterial , Phylogeny , Phytoplasma/genetics , Phytoplasma/physiology , Polymerase Chain Reaction , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Vitis/microbiologyABSTRACT
An elevated blood level of homocysteine (Hcy), a sulfur amino acid, is associated with increased cardiovascular risk. Hcy is generated from S-adenosylhomocysteine (AdoHcy), the demethylated product of S-adenosylmethionine (AdoMet) in transmethylation reactions. AdoHcy is a competitive inhibitor of AdoMet-dependent methyltransferases. AdoHcy accumulation is prevented by rapid metabolism of its products. Chronic renal failure (CRF) is almost constantly associated with hyperhomocysteinemia. It has been shown that: (1) AdoHcy concentration is significantly increased and the AdoMet-AdoHcy ratio is reduced in erythrocytes of patients with CRF; (2) erythrocyte membrane protein methyl esterification, catalyzed by the enzyme protein L-isoaspartyl O-methyltransferase (PCMT; EC 2.1.1.77), is reduced in CRF; PCMT catalyzes a repair reaction involved in the conversion of an isopeptide bond (detrimental to protein structure and function) into a normal peptide bond; (3) D-aspartate residues, a side product of protein methylation and repair, are significantly reduced in erythrocyte membrane proteins of patients with CRF; and (4) folate treatment significantly reduces plasma Hcy levels and improves AdoMet-AdoHcy ratios. Stable isotope studies recently confirmed that the rate of methyl transfer reactions is significantly reduced in uremia. Additional evidence, obtained by independent groups, is consistent with this interpretation. We recently found increased isoaspartyl content of circulating plasma protein levels, particularly albumin, which was only partially reduced after folate treatment, in uremia. This kind of molecular damage possibly is caused by protein increased intrinsic instability as a result of interference with the uremic milieu. In conclusion, Hcy is an uremic toxin involved in protein molecular damage through the inhibition of methylation reactions and protein PCMT-mediated repair.
Subject(s)
Hyperhomocysteinemia/metabolism , Kidney Failure, Chronic/metabolism , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Female , Glomerular Filtration Rate , Humans , Hyperhomocysteinemia/etiology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Methylation , Renal Dialysis , Risk Factors , Sex Factors , Uremia/complications , Uremia/metabolism , Vitamin B 12/metabolism , Vitamin B 6/metabolismABSTRACT
Hyperhomocysteinemia, an independent cardiovascular risk factor, is present in the majority of hemodialysis patients. Among the postulated mechanisms of toxicity, protein homocysteinylation is potentially able to cause significant alterations in protein function. Protein homocysteinylation occurs through various mechanisms, among which is the post-translational acylation of free amino groups (protein-N-homocysteinylation, mediated by homocysteine (Hcy) thiolactone). Another type of protein homocysteinylation occurs through the formation of a covalent -S-S- bond, found primarily with cysteine residues (protein-S-homocysteinylation). Scant data are available in the literature regarding the extent to which alterations in protein homocysteinylation are present in uremic patients on hemodialysis, and the effects of folate treatment are not known. Protein homocysteinylation was measured in a group of hemodialysis patients (n=28) compared to controls (n=14), with a new method combining protein reduction, gel filtration and Hcy derivatization. Chemical hydrolysis was performed, followed by high-pressure liquid chromatography separation. The effects of folate treatment on protein homocysteinylation, as well as in vitro binding characteristics were evaluated. Plasma Hcy, protein-N-homocysteinylation and protein-S-homocysteinylation were significantly higher in patients vs controls. Plasma Hcy and protein-S-homocysteinylation were significantly correlated. After 2 months of oral folate treatment, protein-N-homocysteinylation was normalized, and protein-S-homocysteinylation was significantly reduced. Studies on albumin-binding capacity after in vitro homocysteinylation show that homocysteinylated albumin is significantly altered at the diazepam-binding site. In conclusion, increased protein homocysteinylation is present in hemodialysis patients, with possible consequences in terms of protein function. This alteration can be partially reversed after folate treatment.
Subject(s)
Blood Proteins/chemistry , Blood Proteins/metabolism , Homocysteine/blood , Renal Dialysis , Adult , Aged , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Case-Control Studies , Female , Folic Acid/blood , Folic Acid/therapeutic use , Humans , Hyperhomocysteinemia/blood , Hyperhomocysteinemia/complications , In Vitro Techniques , Male , Middle Aged , Models, Molecular , Protein Binding , Protein Processing, Post-Translational , Serum Albumin/chemistry , Serum Albumin/metabolism , Uremia/blood , Uremia/complications , Uremia/therapy , Vitamin B 12/blood , Vitamin B 6/blood , Xenobiotics/metabolismABSTRACT
Chronic renal failure (CRF) is frequently associated with increased plasma levels of homocysteine (Hcy), an amino acid that can be considered a new uremic toxin according to recent evidence. Studies on Hcy described first homocystinuria, an inherited disease characterized by high plasma Hcy levels and premature cardiovascular disease, resulting in high mortal-ity rates. Hyperhomocysteinemia was then shown to be associated with cardiovascular events both in the general population and in CRF patients. Hcy is a sulfur amino acid derived from dietary methionine, an essential amino acid. Methionine is condensed with ATP to form S-adenosylmethionine (AdoMet), the universal methyl donor in transmethylation reactions. The AdoMet demethylated product is S-adenosylhomocysteine (AdoHcy), which is the direct precursor of Hcy in vivo. Hcy is toxic for the endothelium, it enhances vascular smooth muscle cell proliferation, increases platelet aggregation, and acts on the coagulation cascade and fibrinolysis. Several mechanisms have been discussed to explain Hcy toxicity. Hcy levels increase as renal function declines and progresses to ESRD; the causes of hyperhomocysteinemia are still unclear. Studies in humans show that renal metabolic extraction depends on renal plasma flow; in addition, an alteration of the extrarenal metabolic clearance, depending on uremic toxins, may occur. Among the consequences of hyperhomocysteinemia in renal failure are: impaired protein methylation, with altered protein repair processes; DNA hypomethylation, with an alteration in the allelic expression of genes regulated through methylation; and protein homocysteinylation. Further, this review is dealing with the 'reverse epidemiology' issue, outlining also the main Hcy-lowering strategies.