1,721,077 research outputs found
Nitric oxide in the normal kidney and in patients with diabetic nephropathy.
No full textNitric oxide (NO) is a gas with biological and regulatory properties, produced from arginine by the way of nitric oxide synthases (NOS), and with a very short half-life (few seconds). A "coupled" NOS activity leads to NO generation, whereas its uncoupling produces the reactive oxygen species peroxynitrite (ONOO(-)). Uncoupling is usually due to inflammation, oxidative stress, decreased cofactor availability, or excessive NO production. Competitive inhibitors of NO production are post-translationally methylated arginine residues in proteins, which are constantly released into the circulation. NO availability is altered in many clinical conditions associated with vascular dysfunction, such as diabetes mellitus. The kidney plays an important role in body NO homeostasis. This article provides an overview of current literature, on NO production/availability, with a focus on diabetic nephropathy. In diabetes, NO availability is usually decreased (with exception of the early, hyper filtration phase of nephropathy in Type 1 diabetes), and it could constitute a factor of the generalized vasculopathy present in diabetic nephropathy. NO generation in Type 2 diabetes with nephropathy is inversely associated with the dimethyl-arginine concentrations, which are therefore important modulators of NO synthesis independently from the classic stimulatory pathways (such as the insulin effect). A disturbed NO metabolism is present in diabetes associated with nephropathy. Although modulation of NO production is not yet a common therapeutical strategy, a number of yet experimental compounds need to be tested as potential interventions to treat the vascular dysfunction and nephropathy in diabetes, as well as in other diseased states. Finally, in diabetic nephropathy NO deficiency may be associated to that of hydrogen sulfide, another interesting gaseous mediator which is increasingly investigated
La Nutrizione Artificiale (NA) nel diabete mellito. Parte prima: Fisiologia del metabolismo dei substrati in corso di NA ed effetti del diabete
No full textL’alterata omeostasi dei substrati metabolici (glucosio, lipidi, aminoacidi e proteine), che si verifica del diabete mellito non adeguatamente trattato, è dovuta in primo luogo ad un deficit (assoluto o relativo) della secrezione insulinica, che può essere associato ad una resistenza all’azione dell’ormone. Gli effetti dell’insulina sul metabolismo dei substrati sono infatti molteplici (1-3) (Tab. 1), e, di conseguenza, condizioni di insulino-deficienza e/o di resistenza comportano l’assenza o la riduzione delle attese funzioni fisiologiche dell’ormone.
Le alterazioni nel metabolismo dei substrati energetici indotte da carenza di secrezione/azione insulinica avvengono in generale nella stessa direzione per tutti e tre i gruppi di substrati, anche se con entità differente tra le due forme principali di diabete (di tipo 1 o di tipo 2). Tali alterazioni si manifestano sia nelle condizioni di post-assorbimento (cioè dopo il breve digiuno notturno), sia, e ancor più marcatamente, in corso di alimentazione/nutrizione, quando cioè vengono somministrati substrati di origine esogena, per via enterale o parenterale. Nell’alimentazione fisiologica come pure nella Nutrizione Artificiale (NA), infatti, i substrati esogeni, una volta assorbiti.assorbiti, si mescolano indistintamente nel torrente circolatorio con quelli analoghi di origine endogena, creando condizioni dinamiche di disequilibrio che rappresentano una difficile sfida alle terapie di normalizzazione metabolica
Non essential amino acids usage for protein replenishment in humans: a method of estimation.
No full textBackground. Essential amino acids (EAAs) are key factors in determining dietary protein quality. Their Recommended Daily Allowances (RDAs) have been estimated. However, although non essential amino acids (NEAAs) are utilized for protein synthesis too, no estimates of their usage for body protein replenishment have been proposed so far.
Objective. To provide minimum, approximate estimates, of NEAA usage for body protein replenishment/conservation in humans.
Methods. A correlation between the pattern of both EAAs and NEAAs in body proteins, and their usage, was assumed. In order to reconstruct an “average” amino acid pattern/composition of total body protein(s) (as g amino acid x g protein-1), published data of relevant human organs/tissues (skeletal muscle, liver, kidney, gut and collagen, making up ~74% of total proteins) were retrieved. The (unknown) amino acid composition of residual proteins (~26% of total) was assumed to be the same as the sum of the above-listed organs excluding collagen. Using international EAA RDA values, an average ratio between EAA RDA, and the calculated whole-body EAA composition, was derived. This ratio was then used to back-calculate NEAA “usage” for protein replenishment. The data were calculated also using estimated organ/tissue amino acid turnover.
Results: The individual ratios between WHO/FAO/UNU RDA and EAA content ranged between 1.35 ([phenylalanine+tyrosine]) and 3.68 (leucine), with a mean value of 2.72±0.81 (±SD). In a reference 70-kg subject, calculated NEAA “usage” for body protein replenishment ranged from 0.73 g x day-1 for asparagine, to 3.61 g for proline. Use of amino acid turnover data yielded similar results. Total NEAAs usage for body protein replenishment was ~19 g x day-1 (45% of total NEAA intake), whereas ~24 g x day-1 were used for other routes.
Conclusions: This method may provide indirect, minimum estimates, of the ”usage” of NEAAs for body protein replacement in humans
Are there dietary requirements for dispensable amino acids and if so, how do we assess requirements?
Full text linkPURPOSE OF REVIEW:
Nonessential amino acids (NEAAs) represent a relevant portion of dietary protein(s), yet their requirement(s) has not been determined. Despite their nature as dispensable substrates, should either shortage of any NEAA precursor or impaired synthetic reactions occur, NEAA dietary intake may become insufficient. The purpose of this review is to discuss recent hypotheses and data on individual NEAA requirements and metabolism.
RECENT FINDINGS:
A minimum total NEAA requirement can simply be estimated by subtraction of essential amino acid (EAA) total RDAs, from recommended 'safe' protein intake. By this calculation, NEAA intake would account for two to three times that of the EAAs, under nitrogen-balance conditions. Although the α-amino-nitrogen of the NEAAs is 'not essential', yet it must be furnished by a common pool contributed by both EAAs and NEAAs. Thus, an increased demand for NEAAs may deprive the α-amino-nitrogen body pool(s) possibly limiting the NEAA de novo synthesis itself. Conversely, shortage of NEAAs may require more EAAs to maintain the nitrogen pool. Conditions of increased requirements could those of unbalanced diets, EAA intake below RDA, pregnancy, or else. In addition, the 'obligatory nitrogen losses' may consume NEAAs too. A novel approach to estimate NEAA 'requirements' in humans is proposed.
SUMMARY:
Methods to estimate NEAA requirements in humans should be the object of further studies
Presentazione
No full textIl volume costituisce un manuale per gli studenti dei corsi universitari in Educazione Professionale (nei servizi sanitari) sui temi della disabilita
Ketoacidosis in diabetic subjects treated with inhibitors of Na+-glucose co-transporters type-2: New mechanisms?
No full textKetoacidosis with mild or absent hyperglycemia has been reported in diabetic patients (both type-1 and 2), treated with inhibitors of Na+-glucose co-transporters type-2 (SGLT-2).[1] SGLT-2 enhances sodium and glucose re-absorption against concentration gradient in the proximal renal tubule, whereas SGLT-2 inhibitors cause increased urinary glucose excretion, thus contributing to systemic glucose lowering.
As explanations for ketoacidosis, some hypotheses have been forwarded. The glucose-lowering effect of SGLT-2 inhibitors may lead to the (inappropriate) reduction of insulin dosage, resulting in enhanced lipolysis and ketone body production. In addition, increased tubular reabsorption and decreased renal clearance of acetoacetate,[2] increased glucagon/insulin ratio, depletion of body energy and carbohydrate stores favoring lipolysis, lipid oxidation[3] and ketogenesis, gastroenteritis-induced dehydration, and, finally, a low carbohydrate diet[2] have been proposed. Indeed, it is well known that ketogenesis can be inhibited by glucose.[4]
However, these hypotheses can be integrated by additional considerations involving the sites of both ketone body production and of the SGLT-2 inhibition effects.
The ketone bodies acetoacetate and 3-hydroxybutyrate are mainly produced by the liver, but also by skeletal muscle, particularly in uncontrolled diabetes.[5] While in muscle, the ketogenic capacity is low when expressed per gram of tissue, it may become quantitatively important given the large muscle mass. Conversely, although SGLT-2 expression/activity has been predominantly located in the kidney, they have also been detected in liver and skeletal muscle in human tissues.[6]
Therefore, I would propose the following integrative mechanism: Treatment with SGLT-2 inhibitors, by reducing glucose uptake (both oxidative and nonoxidative) in peripheral tissues,[3] possibly also in liver and muscle, may favor a switch from glucose to lipid utilization, resulting in increased ketogenesis in these tissues. The decrease of systemic glucose concentration is probably the major cause of reduced glucose utilization. However, a possible direct effect of SGLT-2 inhibitors on SGLT-2-mediated glucose uptake in tissues or organs other than the kidney cannot be excluded “a priori,” and might be specifically investigated
Leucine Transamination Is Lower in Middle-Aged Compared with Younger Adults.
No full textBackground: Insulin and age affect leucine (and protein) kinetics in vivo. However, to our knowledge, leucine transamination and the effects of insulin have not been studied in participants of different ages.Objective: The aims of the study were to measure whole-body leucine deamination to α-ketoisocaproate (KIC) and KIC reamination to leucine in middle-aged and younger healthy adults, both in the postabsorptive state and after hyperinsulinemia.Methods: Younger (mean ± SE age: 26 ± 2 y) and middle-aged (54 ± 3 y) healthy men and women were enrolled. Isotope dilution methods with 2 independent leucine and KIC tracers, a dual isotope model and the euglycemic, hyperinsulinemic clamp technique, were used.Results: Leucine deamination [expressed as μmol/(kg × min)] was consistently greater than KIC reamination. In middle-aged adults, postabsorptive leucine deamination (0.77 ± 0.05), reamination (0.49 ± 0.04), and net deamination (0.28 ± 0.04) were ∼30% lower than in the younger group (deamination: 1.12 ± 0.07; reamination: 0.70 ± 0.09; net deamination: 0.42 ± 0.04) (P < 0.002, P < 0.05, and P < 0.015, respectively). After the hyperinsulinemic clamp, plasma leucine and KIC concentrations were reduced by ∼50% in both groups. Deamination and reamination also were suppressed by ∼40-50% in both groups (P < 0.001); however, they remained lower [-35% (P = 0.02) and -25% (P = 0.036), respectively] in the middle-aged than in the younger participants. The leucine rate of appearance and its suppression by insulin were similar in the middle-aged and in the younger subjects. By using both the basal and the clamp data, deamination was directly correlated with the plasma leucine concentration (r = 0.61, P < 0.0025) and reamination to that of plasma KIC (r = 0.79, P < 0.00002). Expressing the data relative to lean body mass did not substantially alter the results.Conclusions: Leucine deamination and reamination are lower in middle-aged than in younger adults, both in the postabsorptive and in the insulin-stimulated state. In middle age, a decreased net leucine transamination may represent a mechanism to spare this essential amino acid
Disabili e Abili. Manuale per Educatori Professionali
No full textIl volume si inserisce nella Collana "Professioni socio-sanitarie e Formazione" diretta dai medici Paolo Tessari e Alessandro Martin.
Contiene i contributi dell'area medica, psicologioca, pedagogica, sociologica, politica.
Fra gli autori: RENZO VIANELLO, SALVATORE SORESI, ANGELO FERRO, GIOVANNI SILVANO, DARIO IANES, GIANMARIA GIOGA, LUIGI PAVAN, ANTONIO CONDINI, PAOLOA SANTONASTASO, ANDREA MARTINUZZI, ATTILIO CARRARO, GUIDO DE RENOCHE, CARLO SCORRETTI, ANDREA PANCALDI, RENZO ANDRICH ECC
Metabolismo Proteico
No full textLe proteine costituiscono elementi fondamentali della struttura di cellule, tessuti, organi. In esse è contenuta la massima parte dell’azoto corporeo1, e, come è noto, la presenza di azoto organico
è sinonimo di “vita”. Le proteine rivestono molteplici ruoli: oltre ad essere elementi costitutivi e strutturali, possono avere funzioni regolatrici (enzimi), di segnale (ormoni, mediatori intracellulari), immunitarie (anticorpi), di trasporto (ad es. albumina, transferrina), ecc. Una buona condizione nutrizionale si accompagna ad un patrimonio proteico “normale”, ovvero mantenuto entro limiti fisiologici. aminoacidico e proteico dell’organismo. Durante un pasto misto (quindi contenente proteine), gli aminoacidi liberati nel lume intestinale dalla digestione delle proteine alimentari e poi assorbiti, si mescolano nel plasma con quelli derivati dal turnover proteico delle proteine dell’organismo
stesso. Tuttavia, proteolisi e sintesi proteica “endogene” vengono modulate dall’ingresso in circolo dei nutrienti, e dalla risposta ormonale e emodinamica ad essi associata. In genere, durante l’assorbimento di un pasto la degradazione proteica endogena viene inibita, mentre la sintesi proteica viene stimolata. Tali due processi combinati si traducono da un lato nel “risparmio” di proteine endogene, dall’altro nella sintesi di nuove proteine, risultando in un deposito proteico positivo “netto”
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