A multi‐centre randomized trial of two different doses of nicotinamide in patients with recent‐onset Type 1 diabetes (the IMDIAB VI)

Background

Intensive insulin therapy is the gold standard by which Type 1 diabetes is treated. In addition to this therapy, administration of nicotinamide (NA) can be beneficial. This concept is reinforced by the results of a recent meta‐analysis of the use of NA in patients with recent‐onset Type 1 diabetes.

Methods

In this study we compared two different doses of NA in 74 patients with duration of Type 1 diabetes <4 weeks (mean age 13 years). Patients were randomly allocated in blind to two treatment groups: 38 patients received a dose of 25 mg/kg (b.w.) of NA and 36 patients received a dose of 50 mg/kg (b.w.) of NA. Intensive insulin therapy was carried out in order to optimize metabolic control as soon as possible after diagnosis and to maintain blood glucose level as near to normal as possible. Response to therapy was monitored throughout the study by investigating the occurrence of clinical (complete) remission defined, according to the recommendations of the International Diabetes Immunotherapy Group, as restoration of normal fasting and post‐prandial blood glucose without any insulin administration for more than 2 weeks. Moreover, the integrated measures of metabolic control (C‐peptide, HbA_1c and insulin dose) were analysed at 3‐ month intervals up to 1 year after diagnosis.

Results

There were no significant differences in the integrated measures of metabolic control between the two NA treated groups either at onset of the disease or at each 3‐month interval up to 1 year after diagnosis, although there was a tendency toward higher insulin dosages in the 50 mg NA group. No significant differences were observed in the rate of clinical remission between the two groups.

Conclusion

We conclude that patients with recent‐onset Type 1 diabetes treated with two different doses of NA, in addition to intensive insulin therapy, show similar residual beta‐cell function 1 year later. Since both doses of NA are likely to be effective in reducing beta‐cell dysfunction, the smaller dose of 25 mg/kg NA would be sufficient as a higher dose may induce insulin resistance. Copyright © 1999 John Wiley & Sons, Ltd.

     

Retention rate of a second line with a biologic DMARD after failure of a first-line therapy with abatacept,tocilizumab, or rituximab: results from the Italian GISEA registry

Clinical Rheumatology - EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of...     

Salivary histamine level as a predictor of periodontal disease in type 2 diabetic and non-diabetic subjects

BACKGROUND: Some previous investigations underscored the role of histamine in periodontal disease, especially in diabetic patients, but the behavior of this inflammatory mediator in the early phases of periodontal involvement remains unclear. The aim of the present study was to correlate the presence of histamine in saliva with clinical parameters in healthy, periodontitis-affected, and diabetic subjects to ascertain whether this amine may serve as a predictive index of periodontal risk. METHODS: For this purpose, subjects were selected as follows: 1) with newly diagnosed type 2 diabetes mellitus; 2) with neither diabetes nor periodontitis; 3) with no diabetes but with chronic, untreated periodontal disease. Histamine salivary levels were measured at the initial time (T0) and after 6, 12, and 24 months using high-performance liquid chromatography. The main periodontal indexes were recorded at the same time intervals. RESULTS: At T0, a very typical shape of the histamine chromatogram was found for all patients of the three groups; at this time, the salivary histamine levels of diabetic patients were increased and comparable to those of healthy patients with periodontal disease, whereas healthy subjects with no periodontitis showed reduced histamine levels. Further controls at 6, 12, and 24 months showed a statistically significant correlation between the increase of salivary histamine and the worsening of the periodontal indexes in diabetic and non-diabetic subjects. CONCLUSION: These results suggest that salivary histamine may serve as a predictive index in the prevention of periodontal disease.     

The protective effect of bergamot oil extract on lecitine-like oxyLDL receptor-1 expression in balloon injury-related neointima formation

Lectin-like oxyLDL receptor-1 (LOX-1) has recently been suggested to be involved in smooth muscle cell (SMC) proliferation and neointima formation in injured blood vessels. This study evaluates the effect of the nonvolatile fraction (NVF), the antioxidant component of bergamot essential oil (BEO), on LOX-1 expression and free radical generation in a model of rat angioplasty. Common carotid arteries injured by balloon angioplasty were removed after 14 days for histopathological, biochemical, and immunohistochemical studies. Balloon injury led to a significant restenosis with SMC proliferation and neointima formation, accompanied by increased expression of LOX-1 receptor, malondialdehyde and superoxide formation, and nitrotyrosine staining. Pretreatment of rats with BEO-NVF reduced the neointima proliferation together with free radical formation and LOX-1 expression in a dose-dependent manner. These results suggest that natural antioxidants may be relevant in the treatment of vascular disorders in which proliferation of SMCs and oxyLDL-related endothelial cell dysfunction are involved.     

Inhibition by prostaglandin PGA1 on the multiplication of influenza virus is a dose-dependent effect

Cyclopentenone prostaglandins (PGs), are strong inhibitors of the multiplicative cycle of a wide variety of enveloped RNA and DNA viruses. Their antiviral activity is generally associated with alterations in the synthesis or maturation of specific virus proteins. In this report, we describe the effect of cyclopentenone PGA1 on the replication of influenza A virus Ulster 73 in LLC-MK2 cells. PGA1 was found to inhibit viral replication in a dose-dependent fashion and virus particle yield was reduced at a PGA1 concentration, which did not suppress protein synthesis in mock-infected cells. The kinetic of late viral protein synthesis was delayed in PGA1-treated cells till 10 h post-infection; after that period, viral polypeptide synthesis appeared to be similar in PGA1-treated as well as untreated cells both infected by Ulster 73 virus. This finding suggests that PGA1 might interfere with one or more events in the viral multiplicative cycle such as protein synthesis and assembly, correct insertion of virus polypeptides into the cell membrane and, or maturation of Ulster 73 virion particles. In particular, inhibition of viral replication in LLC-MK2 cells by PGA1 is accompanied by the induction of a cellular polypeptide of 70K molecular weight. We identified this cell protein as a heat shock protein (HSP) related to the inducible isoform of HSP 70, a polypeptide of 72K molecular weight. Induction of this polypeptide by PGA1 was found to be dose-dependent and a substantial accumulation could be seen at a PGA1 concentration that did not inhibit cell protein synthesis in uninfected cells. HSP 70 synthesis started after the beginning of PGA1 treatment and remained at the same level for at least 10 h, leading us to hypothesize that the delay of production of late Ulster 73 proteins could be the consequence of HSP 70 synthesis. These results suggest that HSP 70 could play a role in the antiviral activity of cyclopentenone PGA1 in LLC-MK2 cells.     

Environmental risk factors for type 1 diabetes in Rome and province.

BACKGROUND: In subjects genetically susceptible to type 1 diabetes, exposure to environmental factors during the gestational period, the neonatal period, and the first years of life is thought to play an important role in triggering the immune process leading to beta cell destruction. AIMS: To investigate risk factors for inhabitants of continental Italy. METHODS: A case-control study of 150 type 1 diabetes cases and 750 control subjects (age range 6-18 years) was carried out in Rome and its province, measuring the exposure to environmental risk factors. RESULTS: Three environmental factors were found to occur significantly more in the diabetic group than in the controls. During the mothers' pregnancies, the one risk factor which proved to be higher in diabetics than in controls was maternal infectious disease. During the neonatal period, no risk factors associated with the disease were detected. During early life, eczema and a short duration of breast feeding (less than three months), occurred significantly more in diabetic cases than controls. CONCLUSION: Eczema and breast feeding for less than three months are risk factors for type 1 diabetes in a southern European population. The type, duration, and mode of treatment for infectious diseases during pregnancy need additional investigation as risk factors for type 1 diabetes.     

CT-MR integrated diagnostic imaging of the oral cavity: neoplastic disease

The oral cavity is a complex anatomical region consisting of different anatomical sites and subsites. Cancer undoubtedly represents the most frequent and relevant disease of this region. Clinical examination is often the first approach to oral cavity tumours. Cross-sectional computed tomography (CT) and magnetic resonance imaging (MRI) play a key role in staging locoregional disease by demonstrating submucosal spread and involvement of deep layers; evaluation of specific pathways of spread to peculiar anatomical subsites is also fundamental information that can be obtained with these techniques. The purpose of this paper is to illustrate CT and MRI findings of anatomical subsites involved by tumours of the oral cavity.