Characteristics of adult- compared to childhood-onset type 1 diabetes.

AIMS: To compare diagnosis characteristics, diabetes management and comorbidities in a population diagnosed with type 1 diabetes in childhood with those in a similar population diagnosed in adulthood to identify disease differences related to the age of diabetes onset. METHODS: This analysis was performed using the T1D Exchange Clinic Registry, a cross-sectional survivor cohort. Retrospectively collected characteristics were compared across the following age-at-diagnosis groups: <10, 10-17, 18-24, 25-39 and ≥40 years. RESULTS: The entire cohort included 20 660 participants [51% female, median (interquartile range) age 18 (14-36) years, 82% non-Hispanic white]. Diabetic ketoacidosis at diagnosis was more common among those with onset in childhood. Participants diagnosed as adults were more likely to be overweight/obese at diagnosis and to have used oral agents preceding type 1 diabetes diagnosis (57%). Current insulin pump use was less frequent in participants diagnosed at older ages. Current glycaemic control, measured by HbA1c , insulin requirements and use of a continuous glucose monitor were not different by age at diagnosis. Coeliac disease was the only comorbidity that was observed to have a different frequency by age at diagnosis, being more common in the participants diagnosed at a younger age. CONCLUSIONS: These results show differences and similarities between type 1 diabetes diagnosed in childhood vs adulthood; notably, there was a tendency for there was a higher frequency of diabetic ketoacidosis at onset in children and a higher frequency of use of oral antidiabetes agents in adults. The data indicate that there is little distinction between the clinical characteristics and outcomes of type 1 diabetes diagnosed in childhood vs adulthood. Optimizing glycaemic control remains a challenge in all age groups, with lower use of insulin pumps impacting those diagnosed as adults.

Complex electrical spiking activity in resistive switching nanostructured Au two-terminal devices.

Networks of nanoscale objects are the subject of increasing interest as resistive switching systems for the fabrication of neuromorphic computing architectures. Nanostructured films of bare gold clusters produced in gas phase with thickness well beyond the electrical percolation threshold, show a non-ohmic electrical behavior and resistive switching, resulting in groups of current spikes with irregular temporal organization. Here we report the systematic characterization of the temporal correlations between single spikes and spiking rate power spectrum of nanostructured Au two-terminal devices consisting of a cluster-assembled film deposited between two planar electrodes. By varying the nanostructured film thickness we fabricated two different classes of devices with high and low initial resistance respectively. We show that the switching dynamics can be described by a power law distribution in low resistance devices whereas a bi-exponential behavior is observed in the high resistance ones. The measured resistance of cluster-assembled films shows a [Formula: see text] scaling behavior in the range of analyzed frequencies. Our results suggest the possibility of using cluster-assembled Au films as components for neuromorphic systems where a certain degree of stochasticity is required.

ZnFe2O4 nanoparticles dispersed in a highly porous silica aerogel matrix: a magnetic study.

We report the detailed structural characterization and magnetic investigation of nanocrystalline zinc ferrite nanoparticles supported on a silica aerogel porous matrix which differ in size (in the range 4-11 nm) and the inversion degree (from 0.4 to 0.2) as compared to bulk zinc ferrite which has a normal spinel structure. The samples were investigated by zero-field-cooling-field-cooling, thermo-remnant DC magnetization measurements, AC magnetization investigation and Mössbauer spectroscopy. The nanocomposites are superparamagnetic at room temperature; the temperature of the superparamagnetic transition in the samples decreases with the particle size and therefore it is mainly determined by the inversion degree rather than by the particle size, which would give an opposite effect on the blocking temperature. The contribution of particle interaction to the magnetic behavior of the nanocomposites decreases significantly in the sample with the largest particle size. The values of the anisotropy constant give evidence that the anisotropy constant decreases upon increasing the particle size of the samples. All these results clearly indicate that, even when dispersed with low concentration in a non-magnetic and highly porous and insulating matrix, the zinc ferrite nanoparticles show a magnetic behavior similar to that displayed when they are unsupported or dispersed in a similar but denser matrix, and with higher loading. The effective anisotropy measured for our samples appears to be systematically higher than that measured for supported zinc ferrite nanoparticles of similar size, indicating that this effect probably occurs as a consequence of the high inversion degree.

Anomalous electrical conduction and negative temperature coefficient of resistance in nanostructured gold resistive switching films.

We report the observation of non-metallic electrical conduction, resistive switching, and a negative temperature coefficient of resistance in nanostructured gold films above the electrical percolation and in strong-coupling regime, from room down to cryogenic temperatures (24 K). Nanostructured continuous gold films are assembled by supersonic cluster beam deposition of Au aggregates formed in the gas phase. The structure of the cluster-assembled films is characterized by an extremely high density of randomly oriented crystalline nanodomains, separated by grain boundaries and with a large number of lattice defects. Our data indicates that space charge limited conduction and Coulomb blockade are at the origin of the anomalous electrical behavior. The high density of extended defects and grain boundaries causes the localization of conduction electrons over the entire investigated temperature range.

Endoscopic gastric submucosal transplantation of islets (ENDO-STI): technique and initial results in diabetic pigs.

The results of transplantation of human donor islets into the portal vein (PV) in patients with diabetes are encouraging. However, there are complications, for example, hemorrhage, thrombosis and an immediate loss of islets through the 'instant blood-mediated inflammatory reaction' (IBMIR). The gastric submucosal space (GSMS) offers potential advantages. Islets were isolated from adult pigs. Recipient pigs were made diabetic by streptozotocin. Donor islets were injected into the GSMS through a laparotomy (Group 1A, n = 4) or endoscopically (Group 1B, n = 8) or into the PV through a laparotomy (Group 2, n = 3). The pigs were followed for a maximum of 28 days. Monitoring of C-peptide in Group 1 indicated that there was minimal immediate loss of islets whereas in Group 2 there was considerable loss from IBMIR. In Group 1, there were significant reductions in mean blood glucose and mean exogenous insulin requirement between pretransplantation and 20 days posttransplantation. In Group 2, there was no significant reduction in either parameter. Insulin-positive cells were seen in the GSMS in Group 1, but not in the liver in Group 2. Endoscopic gastric submucosal transplantation of islets (ENDO-STI) offers a minimally invasive and quick approach to islet transplantation, avoids IBMIR and warrants further exploration.

Long-term controlled normoglycemia in diabetic non-human primates after transplantation with hCD46 transgenic porcine islets.

Xenotransplantation of porcine islets into diabetic non-human primates is characterized by (i) an initial massive graft loss possibly due to the instant blood-mediated inflammatory reaction and (ii) the requirement of intensive, clinically unfriendly immunosuppressive therapy. We investigated whether the transgenic expression of a human complement-regulatory protein (hCD46) on porcine islets would improve the outcome of islet xenotransplantation in streptozotocin-induced diabetic Cynomolgus monkeys. Immunosuppression consisted of thymoglobulin, anti-CD154 mAb for costimulation blockade, and mycophenolate mofetil. Following the transplantation of islets from wild-type pigs (n = 2) or from 1,3-galactosyltransferase gene-knockout pigs (n = 2), islets survived for a maximum of only 46 days, as evidenced by return to hyperglycemia and the need for exogenous insulin therapy. The transplantation of islets from hCD46 pigs resulted in graft survival and insulin-independent normoglycemia in four of five monkeys for the 3 months follow-up of the experiment. One normalized recipient, selected at random, was followed for >12 months. Inhibition of complement activation by the expression of hCD46 on the pig islets did not substantially reduce the initial loss of islet mass, rather was effective in limiting antibody-mediated rejection. This resulted in a reduced need for immunosuppression to preserve a sufficient islet mass to maintain normoglycemia long-term.

The pig as the donor of pancreatic islets for men.

The promising results obtained using the "Edmonton protocol" for human islet transplantation has resulted in increased interest and growth of various clinical and basic science programs worldwide. Despite these encouraging results two major drawbacks remain: first, the immunosuppressive regimen necessary to prevent the rejection of this allotransplant dramatically affects the lifestyle of the treated patients precluding its implementation in younger diabetic individuals. Second, there continues to be an inadequate amount of islet tissue available to fulfill the needs of an increasing population of diabetic patients possibly interested in receiving this type of treatment. Besides the limited number of cadaveric organ donors, the current procedure used to isolate islets from their pancreata activates metabolic processes that promote the loss of beta cells in the islets. Thus, it becomes necessary to use more than one donor for a single recipient. To fulfill the continuously growing need for more transplantable islets, an immediately available, unlimited source of islets may be found in animals, which are able to produce a type of insulin that is very similar to the human one, and carry islets in quantities that may satisfy the metabolic requirements of diabetic patients: the pigs.

Glycerophospholipids and cholesterol composition of bile in bile-fistula rats treated with monensin.

Data regarding the action of monensin on the concentrations of glycerophospholipids and cholesterol in bile of rats subjected to total biliary diversion for 3 h are reported. After monensin their concentration in bile drops significantly in the first 60 min collections with respect to the control. Differences seem to be produced between the rates of transport to the bile of glycerophospholipids and cholesterol, not sufficiently explained by the inhibition of bile salt uptake determined by monensin at the sinusoidal pole of the hepatocyte.

Thioacetamide impairs retinol storage and dolichol content in rat liver cells in vivo.

The aim of this paper was to ascertain whether chronic pretreatment with thioacetamide (TAA) might alter the uptake of a load of retinol and dolichol distribution in hepatocytes (HC), hepatic stellate cells (HSC) (Ito-1 and Ito-2 subfractions), Kupffer (KC) and sinusoidal endothelial cells (SEC). The reason why retinol and dolichol content was studied is that their metabolism and transport might be interrelated and that the two isoprenoids might exert different functions in the cells of the hepatic sinusoid. Rats were treated for 2 and 4 months with TAA, a known fibrogenic hepatotoxin, at a low dosage, to produce an early stage of damage. Three days before sacrifice, the rats were given a load of vitamin A, and cells were isolated to investigate its uptake. In HC, the load of retinol was taken up and accumulated, while a decrease in dolichol preceded retinol increase. In HSC, much less of the retinol load was stored than in controls, and dolichol content also decreased. Various minor modifications were seen in KC and SEC.Collectively, the results show that the distribution of these two isoprenoids, which play important roles in cellular differentiation and proliferation, is differently altered in the multiple cell types that line the hepatic sinusoid, and that both isoprenoids seem to participate in the first steps of liver damage.

Serum thyroglobulin levels in the diagnosis and follow-up of subacute 'painful' thyroiditis. A sequential study.

Serum thyroglobulin (Tg) levels were elevated in 92% of 38 patients with subacute "painful" thyroiditis in the early stage, independent of the extent of the disease and thyroid hormone concentrations. After two months of corticosteroid treatment, serum Tg levels were significantly decreased in 25 patients who could be rechecked, compared with the levels in the acute phase, although higher than those in our normal control subjects. Twelve of 25 patients underwent sequential measurements of Tg for three to four months, during the disease and after recovery. In ten the initially elevated values decreased rapidly to normal and were maintained for approximately 20 days. Then they rose gradually, peaked about 60 days after disease onset, then returned slowly and permanently to normal. In one patient who had a clinical relapse during the plateau phase, the Tg level also increased markedly and abruptly. Therefore, serial measurements of serum Tg can help in diagnosing and monitoring subacute "painful" thyroiditis.

[Acute or sub-acute thrombosis of steel stents]. / Thrombose aiguë ou subaiguë des stents en acier. A propos d'une série consécutive de 2 997 patients.

The use of coronary endoprostheses has greatly contributed to the improvement in the results of coronary angioplasty. Nevertheless, the risk of stent thrombosis remains a major preoccupation. We studied a retrospective series of 2997 patients who had undergone coronary angioplasty between 1999 and 2003. 36 patients (1.2%) had an acute or sub-acute stent thrombosis, occurring in two thirds of cases in the first 4 days with particularly serious clinical consequences: 5 deaths (13.8%) and 27 myocardial infarctions (75%). A comparison between the 2 groups of patients with thrombosis (n = 36) and without thrombosis (n = 2961) using multivariate analysis determined predictive factors for thrombosis: systolic LV dysfunction < 40% (p < 0.0001 OR 3.8 [2-7.3]), angioplasty for lesions on the anterior interventricular artery (p < 0.0001 OR 2.7 [1.4-5]), angioplasty performed in the acute phase of MI (p < 0.05 OR 13.9 [6.7-29.2]), B2-type complex lesions (p < 0.01 OR 2.5 [1.3-5]), residual dissection at the dilated site (p < 0.02 OR 5.1 [1.4-18.2]). More than ever, acute thrombosis remains a topical subject. This study emphasises the incidence of steel stent thrombosis; the clinical consequences and the predictive factors for early occlusion.

Evaluation of peritoneovenous shunt patency with Tc-99m labeled microspheres.

The LeVeen peritoneovenous shunt (PVS) was investigated in 40 cirrhotic patients with refractory ascites. Five millicuries of Tc-99m-tagged human albumin microspheres (15-36 microns) were injected into the peritoneal cavity between the umbilicus and the left anterior superior iliac spine. The radiotracer was always detectable by scintigram in the lungs when the shunt was patent. In case of malfunction, by contrast, the radioactivity was either restricted to the venous tube or confined below the diaphragm for at least 4 hr. In the presence of complete obstruction, whereas the tube was not visualized after peritoneal injection, it was outlined by direct injection of 2 mCi of Tc-99m albumin microspheres into its subcutaneous tract, where it crossed the 12th rib, immediately above the valve. This technique sufficed to establish whether the site of obstruction was at the valve or in the tubing itself. In one patient, poor visualization of the tube and a delayed image of the lungs was caused by partial occlusion of the valve with fibrinoid debris. This radiotracer method proved simple, quick, and led to an immediate selective replacement when the shunt was not patent. Therefore, the use of this test is recommended for a definitive diagnosis, since there were neither false negatives nor false positives. No complications such as embolism or bacterial infection were encountered with Tc-99m human albumin microspheres, which are excellent tracers.

Cerebral and cerebellar diaschisis following carbamazepine therapy.

1. The regional cerebral blood flow was studied by SPECT in patients with partial epilepsy before and after 30 days of monotherapy with carbamazepine (CBZ). 2. Both a qualitative visual interpretation and a semiquantitative analysis of SPECT was performed. All patients underwent EEG, CT scan, and MRI studies. The CBZ serum concentrations were assayed. 3. After therapy, in three patients with focal epilepsy, both a crossed cerebral and cerebellar diaschisis were observed, with respect to the side of the epileptic focus in the opposite hemisphere. No morphologic changes were detected at MRI in the cerebral or cerebellar remote hypometabolic areas found at SPECT. 4. CBZ may have a depressant action on the corticopontocerebellar pathways and on the corticocallosal connections.

Glibenclamide partly reverses monesin inhibition of insulin secretion, in vivo.

Glibenclamide, a second generation sulfonylurea, is an oral hypoglycemic drug. It seems to act mainly on the ATP-driven K(+)- channels of the beta-cells of pancreas determining insulin secretion. Because monensin, a Na+/H+ antiport, is able when administered to rats in vivo to inhibit insulin secretion, the action of glibenclamide is studied on glycemia and insulinemia to verify if it can antagonize the action of monensin. The results show that glibenclamide is able to partly reverse ionophore induced hyperglycemia and the inhibition of insulin secretion. These results might be interpreted as if glibenclamide only reverses the ATP-driven K(+)- channel dependent insulin secretion. Moreover the antagonist action of glibenclamide is slightly delayed when both drugs are administered together. The role of Na+/H+ antiport in basal insulin secretion is discussed.

Effect of monensin on insulin and glucose concentration in rat serum.

The effect of monensin, an electroneutral ionophore that exchanges Na+ for H+, is investigated on glucose and insulin concentration in serum of female rats. After monensin administration hyperglycemia is observed. Hyperglycemia is concentration and time dependent. In fact serum glucose starts increasing with 0.5 mg/kg b.w. of monensin and increases sharply till 2.5-3.0 mg/kg b.w. The timing of the appearance shows an increase already after few minutes and keeps increasing reaching its maximum between 30-120 minutes. Hyperglycemia is reversed by insulin; if not treated spontaneously it returns to normality in 4-5 hours. An inverse correlation is observed between insulinemia and glycemia. A significant fall in serum insulin concentration can be observed, with or without glucose-stimulation of insulin release, already after five minutes of treatment. Insulinemia returns to normal values after about two hours. The action of monensin on glycemia might therefore be a reversible inhibition of insulin secretion by the beta-cells of the pancreas.

Dolichol and vitamin A content in rat liver Ito (perisinusoidal) cells.

Dolichol has been determined in many tissues but to date no data are available on liver Ito (fat storing) cells. In this note dolichol was determined in two subpopulations of liver Ito cells isolated from rats pretreated with vitamin A: Ito-1, vitamin A enriched and Ito-2, relatively poor of vitamin A. Differences were observed in the behaviour of the two fractions after vitamin A pretreatment of rats. In fact, in Ito-1 fraction dolichol increases with the increase of vitamin A, while in Ito-2 fraction it does not change significantly with the increase of vitamin A. These results, while confirming the heterogeneity of fat storing cells, are discussed as to the possible role of dolichol and vitamin A metabolism.

Dolichol and retinol content of rat liver sinusoidal cells after chronic monensin treatment.

Aim of this study was to ascertain whether an impairment of communication between parenchymal and non-parenchymal liver cells involves vitamin A intercellular transport. The following approach was adopted: liver cells were isolated from rats treated chronically with the hydrophobic ionophore monensin i.p. for 3, 5, and 7 weeks and their retinol and dolichol content was assessed. Monensin, which alters membrane flow, was used because it had previously been reported to induce liver steatosis, cholestasis and glycogenolysis after acute treatment and, by preliminary morphological examination, to impair vitamin A transport between stellate cells and hepatocytes. Dolichol was chosen as a biochemical marker because it is a membrane lipid that modulates the fluidity and permeability of the membranes that retinol must cross. After monensin treatment, a load of vitamin A was given to rats three days before sacrifice, to ascertain whether its uptake by sinusoidal liver cells was altered. The main result was a dolichol decrease in hepatocytes and in the Ito-1 subfraction. In this latter, monensin induced a decrease in dolichol content only after vitamin A load. Moreover, while the hepatocytes were able to take up a load of vitamin A normally, the Ito-1 subfraction was no longer able to store retinol. Therefore the polarised transport of retinol between hepatocytes and stellate cells seemed impaired. The behaviour of sinusoidal endothelial cells and Kupffer cells might be ascribed to the functions of these cells and is not significantly modified by monensin. In conclusion, the altered cross-talk between sinusoidal cells in liver pathology might involve retinol as well as cytokines. Different pools of dolichol might have a role in this membrane process in a hydrophobic environment.

Action of chronic CC14 on the retinol and dolichol content of rat liver parenchymal and non-parenchymal cells.

We studied dolichol, on account of its role in membrane fluidity and fusion, and retinol, on account of its behaviour in liver fibrosis, in isolated parenchymal and sinusoidal rat liver cells after CCl4 treatment for 3, 5 and 7 weeks. Retinol uptake was also investigated by administering a load of retinol three days before sacrifice. In hepatocytes, dolichol decreased and seemed to be the preferred target of lipid peroxidation by CCl4; indeed, retinol increased especially after vitamin A load. Two subfractions of hepatic stellate cells were obtained: in the subfraction called Ito-1, dolichol decreased, while the supplemented retinol was no longer stored; in the subfraction called Ito-2, the values were intermediate. In Kupffer and endothelial cells dolichol was higher after three weeks, in agreement with fibrogenesis. Retinol increased after retinol load, in Kupffer and endothelial cells, in agreement with their scavenger function. The different behaviour of dolichol content in parenchymal and non-parenchymal cells suggests that dolichol may have different functions in liver cells. Since it has been ascertained that, in liver fibrosis, stellate cells gradually lose retinol, the inability of HCs to send retinol to Ito-1 subfraction or the inability of Ito-1 subfraction to take up and store vitamin A might induce or contribute to the transformation of these cells into a different phenotype. This behaviour is discussed regarding the role of cellular and retinol binding proteins in intracellular retinol content. Moreover a role of dolichol in membrane fluidity and retinol traffic is hypothesised.

Beta-endorphin and cortisol levels in plasma and CSF following acute experimental spinal traumas.

beta-endorphin and cortisol were measured in cerebrospinal fluid (CSF) and plasma by radioimmunological method (RIA) in two groups of rabbits with spinal cord traumatic injuries at cervical and lumbar levels, respectively with and without concomitant spinal shock and arterial hypotension, and in a group of sham operated animals as controls. The two groups with spinal lesions displayed a significant beta-endorphin increase in CSF, whereas the cortisol level remained unchanged both in the spinal traumatized rabbits and in controls. Both the opioid and the cortisol concentration rose significantly in plasma in all three groups and in particular resulted significantly higher in the cervical traumatized group where spinal trauma was associated with spinal shock and hypotension. However, no significant difference was found when beta-endorphin concentrations in plasma were compared between the sham operated animals and the spinal lumbar traumatized animals without concomitant spinal shock. The results seem to suggest that the beta-endorphin increase in CSF is related to the nervous tissue lesion, while its increase in plasma, like that of cortisol, is due to surgery or other stress factors inherent in the experiment. This independent behaviour of beta-endorphin in plasma and in CSF suggests its different origin in these two compartments.

Role of 131Cs scan in preoperative diagnosis of nonfunctioning thyroid nodules.

The role of 131Cs scan in the preoperative diagnosis of cancer was evaluated in 355 patients with either cold or nonfunctioning thyroid nodules. Nodules were classified as positive, doubtful or negative by the pattern of isotope accumulation. Among 234 patients who underwent thyroidectomy, malignant lesions were found in 10.2 per cent of cases. All carcinomas but one found during surgery had been classified as positive by radiocesium scan and were considered as highly suspicious preoperatively; one carcinoma and two papillary adenomas had been classified doubtful and considered presumably malignant. False-positive nodules were found. However, we did not document histologically malignant lesions in nodules which were classified as negative by radiocesium uptake. The routine use of 131Cs scanning may be very useful in patients with cold or nonfunctioning thyroid nodules because of its high sensitivity in excluding malignant lesions.