Immunogenicity of advanced glycation end products in diabetic patients and in nephropathic non-diabetic patients on hemodialysis or after renal transplantation.

Advanced glycation end products (AGE) increase as a consequence of diabetic hyperglycemia and, in nephropathic patients, following renal function loss. Protein-bound AGE behave as immunogens, inducing formation of specific antibodies (Ab-AGE). In this work AGE immunogenicity was studied in 42 diabetic patients, 26 nephropathic patients on hemodialysis and 26 patients with end-stage renal disease who underwent kidney transplantation and in 20 normal subjects. Non-oxidation-derived AGE (nox-AGE), oxidation-derived AGE (ox-AGE) and Ab-AGE were measured by competitive or direct enzyme-linked immunosorbent assay (ELISA) and circulating immune complexes (CIC) by C1q ELISA. Nox- AGE increased significantly in all patient groups (p < or = 0.05 to < or = 0.0001) except in patients on hemodialysis for less than 6 yr. Ox-AGE were only significantly increased in patients transplanted more than 3 yr previously (p < 0.05). Ab-AGE were significantly lower than controls in both diabetic groups and in patients on hemodialysis for more than 6 yr (p < 0.005 to < 0.0001) and not unlike controls in the other groups. These results demonstrate that hemodialysis or renal transplantation can, initially, reduce either nox- or ox-AGE levels, which however go back to being high in time. Renal transplantation fails to normalize nox-AGE. More importantly, plasma Ab-AGE levels are reduced or unchanged in all patient groups in comparison with controls, despite higher circulating AGE levels. This suggests the importance of tissue-bound AGE as Ab-AGE targets. Additional interventions are needed to control AGE levels in treated nephropathic patients. The search and quantification of specific Ab-AGE would give more meaningful results if performed over specific tissue specimens.

[Vasoactive intestinal peptide in heart failure]. / Il peptide vasoattivo intestinale nello scompenso cardiaco.

BACKGROUND: The aim of our study was to investigate the pathophysiological role of the vasoactive intestinal peptide (VIP), a vasodilating neuropeptide with positive inotropic and chronotropic properties, in heart failure. METHODS: The study was carried out in 35 patients with heart failure due to dilated cardiomyopathy, who underwent a peripheral venous blood sample for radioimmunoassay of VIP within the first in-hospital day. RESULTS: The plasma concentration of VIP: 1) is not higher than normal in the whole group of patients with heart failure; 2) is higher in younger than in elderly healthy subjects but does not significantly change in relation to age in heart disease patients; 3) is higher in elderly (> 60 years) but not in younger (< 60 years) patients compared to healthy subjects of the same age; 4) is higher in NYHA functional class 2 than in NYHA functional class > 2 groups and in normal subjects; 5) is not correlated with echocardiographic parameters; 6) does not significantly change with respect to the etiology of dilated cardiomyopathy. CONCLUSIONS: The plasma concentration of VIP in heart failure is conditioned by some epidemiological and clinical variables. Unlike the healthy group, differences are not detectable with respect to the age of patients; thus, in elderly heart disease subjects the neuropeptide productive potentiality is preserved. Taking into account the physiological properties of VIP, its plasma increase in the initial phase of heart failure can be reasonably regarded as a further mechanism to restore the compromised hemodynamic balance. Its decrease, related to worse clinical conditions, could be due to a progressive depletion from the pre-synaptic nerve endings and to a deficiency in the neurogenic productive capacity of the molecule.

[Diabetes and pregnancy: physio-pathogenetic and epidemiologic aspects]. / Diabete e gravidanza: aspetti fisio-patogenetici ed epidemiologici.

Diabetes mellitus is one of the most common maternal illnesses resulting in congenital malformations. All complications of pregnancy, either with diabetes pregestational or gestational, are directly or indirectly related to the degree of metabolic control. If it is not treated properly, diabetes in pregnancy causes major problems for both mother and fetus. The only way to reduce complications to the minimum and locate them near to those of the normal population, is to achieve a good metabolic control. Multi-disciplinary approach in which obstetricians, physicians, paediatricians are involved, combined with intensive monitoring and therapy throughout pregnancy, could achieve successful results in women with complicated diabetes. This objective is subordinate to early diagnosis for gestational diabetes and planning of pregnancy for diabetic women.

Telemedicine in the treatment of diabetic pregnancy.

Good diabetic control requires that treatment be continuously adapted to the patient behavior. We investigated whether the use of telemedicine could present an advantage to the management of the diabetic woman during pregnancy. A system completely automatic (DIANET system) was used. Twenty IDDM women participated in the study: 10 treated by telemedicine and 10 by conventional system, at times "entry" (9.5 weeks), "basal" (9.5-16.8 weeks), "1st month" of investigation, and "end" (near delivery). All women used intensified protocols of insulin administration. The treatment with DIANET vs conventional showed a better metabolic control as estimated by profile of blood glucose absolute values (at time "end": values significantly lower before breakfast: 87 +/- 6 vs 104 +/- 4 mg, lunch: 85 +/- 5 vs 104 +/- 4 mg, and after dinner: 102 +/- 5 vs 124 +/- 6 mg). These results were associated with higher insulin doses in the DIANET vs conventional treatment, and a significant reduction of hypoglycemic reaction in both group. Our results suggest that telemedicine-DIANET is a practical way of providing specialist care in the pregnancy area.

Levels of advanced glycosylation end-products (AGE) in sera of pregnant diabetic women: comparison between type 1, type 2 and gestational diabetes mellitus.

The chronic hyperglycemia can lead to an increase of the advanced glycosylation end-products (AGE) levels on proteins and macromolecules. Abnormal levels of AGE in several tissues has been associated with the pathogenesis of late diabetic complications. In diabetic pregnant women, high AGE levels might influence the delicate maternal-fetal balance and therefore alter the pregnancy outcome. In this preliminary study, we have measured the AGE in sera of 44 diabetic women in two trimester. Sixteen sera from non diabetic pregnant women have been used as controls. The AGE have been analyzed by means of an ELISA method with an antiserum anti-RNAse-AGE, produced in the Laboratory of Clinical Biochemistry of the Istituto Superiore di Sanità. Diabetic patients type 1 and type 2, in good metabolic control, showed normal AGE levels at both trimester. Patients with gestational diabetes showed significantly high serum AGE levels (p < 0.05). A more extended study will give better insight on the association between AGE levels and a physiopathology of diabetic pregnancy.

IGF-1 levels in diabetic pregnant women and their infants.

Plasma IGF-1 was measured in 38 diabetic pregnant women (DPW) and in 12 non diabetic pregnant women (NDPW) during the 1st, 2nd and 3rd trimester of pregnancy. IGF-1 was measured in the cord blood of 24 infants of diabetic mothers (IDDM) and IGF-1 in 11 infants of non diabetic mothers (NIDDM). A progressive and significant (p < 0.0001) increase of IGF-1 values was found throughout the pregnancy both in DPW and NDPW IGF-1 (149 +/- 18 ng/ml vs 181 +/- 14 ng/ml, 184 +/- 17 ng/ml vs 232 +/- 25 ng/ml, 279 +/- 20 ng/ml vs 325 +/- 17 ng/ml). Furthermore IGF-1 decreased significantly soon after delivery in both groups of women. In type 1 diabetic pregnant women IGF-1 values were significantly lower than the controlled non diabetic patients. IGF-1 in the cord blood was significantly higher in IDDM than in NIDDM 86 +/- 7 ng/ml and 62 +/- 7 ng/ml respectively (p < 0.03). In addition, DPW plasma levels IGF-1 were positively correlated with the weight of the placenta (r = 0.233, p < 0.03) and negatively correlated with the diabetes duration (r = 0.412, p < 0.05). No correlations were found between IGF-1 cord blood concentrations and gestational age, birth weight and length, but there was a significant correlation with weight percentile (r = 0.846, p < 0.001). No correlation was found between maternal IGF-1 plasma levels and other parameters like insulin need, weight gain, metabolic control and time of delivery.

[Neuroendocrine activation in acute myocardial infarction: state of the art and preliminary results on intestinal vasoactive peptide]. / Attivazione neuroendocrina nell'infarto acuto del miocardio: stato dell'arte e risultati preliminari sul peptide vasoattivo intestinale.

Acute myocardial infarction (AMI) is known to be associated with a complex neuroendocrine activation, especially concerning sympathetic and renin-angiotensin systems, cortisol, atrial natriuretic peptide and endothelin. Results of our study show that the vasoactive intestinal peptide (VIP), also, is early involved in the neuroendocrine activation occurring in AMI. Plasma concentration of VIP, significantly increased in AMI patients within 6 hours after the onset of chest pain, soon decreased and remained below than normal along the first week. At the 14th day of the AMI, plasma levels of VIP returned into the normal range. A significant increase of VIP plasma concentration is detectable in the first hours of AMI in survived as compared with died patients. The phenomenon seems to be a suitable process to provide an endogenous support to the ischemic heart and to counteract the negative effects of other neuroendocrine activated factors.

[Somatomedins/insulin-like growth factors (IGFs): chemical and functional characteristics]. / Somatomedine/fattori di crescita insulino-simili (IGFs): caratteristiche chimiche e funzionali.

The insulin-like growth factors constitute a family of peptides which have structural homology with proinsulin, and which possess broad anabolic and mitogenic action in wide variety of tissues. The two main forms of IGFs in serum of adults are insulin-like growth factor I (IGFI) and insulin-like growth factor II (IGFII). IGFI appears to be the major growth factor involved in postnatal growth and is believed to mediate most (if not all) of the growth promoting effects of growth hormone (GH). IGFII may be involved in embryonic and fetal growth. It is the aim of this article to present an account of recent advances in the understanding of the origins, functions, and clinical significance of these peptides. Particularly the role of IGFs in fetal growth during normal and diabetic pregnancies.