Systemic use of non‐biologic corticosteroids in orofacial diseases

Systemic non‐biologic agents have long been in clinical use in medicine – often with considerable efficacy, albeit with some adverse effects – as with all medications. With the advent of biologic agents, all of which currently are restricted to systemic use, there is a growing need to ensure which agents have the better therapeutic ratio. The non‐biologic agents (NBAs) include a range of agents, most especially the corticosteroids (corticosteroids). This study reviews the corticosteroids in systemic use in management of orofacial mucocutaneous diseases; subsequent studies discuss corticosteroid‐sparing agents used in the management of orofacial diseases, such as calcineurin inhibitors used to produce immunosuppression; purine synthetase inhibitors; and cytotoxic and other immunomodulatory agents.     

Diet,cow's milk protein antibodies and the risk of IDDM in Finnish children

Summary Associations of infant feeding patterns and milk consumption with cow's milk protein antibody titres were studied in 697 newly-diagnosed diabetic children, 415 sibling-control children and 86 birth-date-and sex-matched population-based control children in the nationwide Childhood Diabetes in Finland study. IgA and IgG antibody titres to the proteins of cow's milk formula, BLG and BSA, and IgM antibody titres to cow's milk formula proteins were measured by ELISA. Several inverse correlations were observed between the duration of breast-feeding or age at introduction of dairy products and antibody titres, and positive correlations were observed between milk consumption and antibody titres in all three populations studied. Multivariate analyses which included the infant feeding variables, milk consumption and current age simultaneously showed that the earlier the introduction of dairy products and the greater the consumption of milk was, the higher several antibody titres were. High IgA antibody titres to cow's milk formula were associated with a greater risk of IDDM both among diabeticpopulation-control and diabetic-sibling-control pairs when adjusted for other cow's milk antibody titres, dietary variables and in diabetic-sibling-control pairs also for ICA. The results suggest that young age at introduction of dairy products and high milk consumption during childhood increase the levels of cow's milk antibodies and that high IgA antibodies to cow's milk formula are independently associated with increased risk of IDDM.Abbreviations IDDM Insulin-dependent diabetes mellitus - BLG betalactoglobulin - BSA bovine serum albumin - ICA islet cell antibodies - IAA insulin autoantibodies - OR odds ratio - CI confidence interval     

Neuropeptide Y and Y2‐receptor are involved in development of diabetic retinopathy and retinal neovascularization

BACKGROUND: Neuropeptide Y is a sympathetic neurotransmitter, a potent endothelium‐derived angiogenic factor and a vascular mitogen. We have studied the role of the functional leucine7 to proline7 polymorphism of the signal peptide region of preproneuropeptide Y (prepro‐NPY) as a genetic susceptibility factor for diabetic retinopathy. In addition, we investigated the role of the NPY Y2‐receptor as a putative mediator of angiogenic NPY signaling in the retina.

METHODS: Frequencies of proline7 (Pro7) carriers in the prepro‐NPY were determined in type 1 and type 2 diabetes patients having retinopathy, in type 2 diabetes patients without retinopathy and in healthy control subjects. The role of Y2‐receptor in hyperoxemia‐induced retinal neovascularization was investigated in Y2‐receptor knockout mice (Y2 ^?/? ) and in rats administered Y2‐receptor mRNA antisense oligonucleotide.

RESULTS: The carriers having Pro7 in the preproNPY are markedly over‐represented among type 2 diabetes patients with retinopathy compared to type 2 diabetes patients without retinopathy and to the population control. Neonatal exposure to hyperoxia resulted in development of retinal neovascularization that was prevented in Y2 ^?/? ‐mice, and significantly inhibited in rats treated with the Y2‐receptor antisense oligonucleotide.

CONCLUSIONS: NPY and Y2‐receptor play important roles in diabetic retinopathy and retinal neovascularization and are thus potential new targets for drug molecules for treatment of retinopathy.     

Post‐trial costs,clinical outcomes,and dental service utilization after a randomized clinical trial for caries control among Finnish adolescents

Hietasalo P, Seppä L, Niinimaa A, Kallio J, Lahti S, Hausen H. Post‐trial costs, clinical outcomes, and dental service utilization after a randomized clinical trial for caries control among Finnish adolescents. Eur J Oral Sci 2010; 118: 265–269. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci The aim of this study was to assess post‐trial treatment costs, clinical outcomes [decayed, missing or filled surfaces (DMFS) scores], and utilization of dental services among adolescents who had participated in a randomized clinical trial (RCT) in Pori, Finland, in 2001–2005. At baseline the children were 11–12 yr of age and had had at least one active initial caries lesion. The children in the experimental group (n = 250) had been exposed to multiple measures for caries control, while those in the control group (n = 247) had received standard dental care. During the post‐trial period (2005–2008), all participants received the standard dental care offered in public dental clinics in Pori. In both groups the costs of treatment procedures and outcomes for the post‐trial period were calculated for each adolescent. Information from patient records was available for 487 adolescents (former experimental n = 246, control n = 241). The mean total costs per adolescent were lower and the clinical outcome was better among the former experimental‐group participants. The differences in mean costs between the groups were statistically significant for preventive and restorative procedures. The utilization of dental services was significantly more regular among the former experimental‐group participants.     

Role of angiogenic growth factors in transplant coronary artery disease

Transplant coronary artery disease (TxCAD) as a manifestation of chronic rejection is a major limitation to long‐term survival of heart transplant recipients. Although the exact molecular and cellular mechanisms contributing to neointimal formation are unknown, it has been generally believed that smooth muscle cells (SMC) of donor origin migrate from the media into the subendothelial layer of the vascular wall, where SMC proliferate and synthesize extracellular matrix resulting in intimal thickening. However, recent observations indicate that hematopoietic and vascular progenitor cells derived from recipient bone marrow may contribute to the arteriosclerotic lesion formation in the coronary arteries of the transplant. On the other hand, studies on postnatal hematopoiesis indicate that angiogenic growth factors such as vascular endothelial growth factor (VEGF) and angiopoietin‐1 (Ang1) may regulate the recruitment of these cells into distant organs. Furthermore, embryonic VEGFR‐2 ⁺ /CD34 ⁺ stem cells may serve as vascular progenitor cells and their differentiation into endothelial cells and SMC may be regulated by VEGF and platelet‐derived growth factor (PDGF), respectively. In this review, we discuss the role of angiogenic growth factors such as VEGF, Ang, and PDGF in the recruitment of hematopoietic and vascular progenitor cells in TxCAD and suggest novel therapies targeted at homing, differentiation and proliferation of these cells in the allograft.     

Blackcurrant seed oil for prevention of atopic dermatitis in newborns: a randomized,double‐blind,placebo‐controlled trial

Background The present increased incidence of atopic diseases has been associated with an altered intake of essential fatty acids (EFAs). The composition of blackcurrant seed oil (BCSO) corresponds to the recommended dietary intake of EFAs, and as a dietary supplement could, in small doses, modify the imbalance of EFAs in an efficient way. Objective To assess the effect of dietary supplementation with BCSO on the prevalence of atopy at 12 months of age. Methods Three hundred and thirteen pregnant mothers were randomly assigned to receive BCSO (151) or olive oil as placebo (162). The first doses were administered at 8th–16th weeks of pregnancy and were continued until the cessation of breastfeeding, followed by supplementation to the infants until the age of 2 years. Atopic dermatitis and its severity (SCORAD index) were evaluated, serum total IgE was measured and skin tests were performed at the age of 3, 12 and 24 months. Results Parental atopy was common (81.7%) among study subjects, making them infants with increased atopy risk. There was a significantly lower prevalence of atopic dermatitis in the BCSO group than in the olive oil group at the age of 12 months (33.0% vs. 47.3%, P=0.035). SCORAD was also lower in the BCSO group than in the olive oil group at 12 months of age (P=0.035). No significant differences in the prevalence of atopic dermatitis were observed between the groups at the age of 24 months (P=0.18). Conclusion Dietary supplementation with BCSO was well tolerated and it transiently reduced the prevalence of atopic dermatitis. It could therefore be one potential tool in the prevention of atopic symptoms when used at an early stage of life. (Registration number SRCTN14869647, http://www.controlled‐trials.com ) Cite this as: P. Linnamaa, J. Savolainen, L. Koulu, S. Tuomasjukka, H. Kallio, B. Yang, T. Vahlberg and R. Tahvonen, Clinical & Experimental Allergy, 2010 (40) 1247–1255.     

Carotid Intima-Media Thickness after Pediatric Renal or Liver Transplantation at High-Resolution B-Mode Ultrasonography

In a previous study, we observed a higher incidence of dyslipidemia in pediatric renal recipients compared with liver recipients. In the present study, we measured common carotid artery intima-media thickness (IMT) in 13 pediatric renal recipients, 9 liver recipients, and 26 control individuals with median age of 11.4, 10.8, and 12.0 years, respectively. The patients were studied from 0.2 to 10.8 years after renal transplantation (RTx) or liver transplantation (LTx). An experienced radiologist (T.K.) blinded to the status of the children measured the IMT using a high-resolution B-mode ultrasonography method. In patients who underwent RTx or LTx, serum fasting lipid profile, estimates of renal and liver function, and glucose metabolism were determined. Children undergoing RTx or LTx more often had hypertension compared with the control individuals (P = .004). Before transplantation, dyslipidemia was greater in patients undergoing RTx compared with those undergoing LTx (P < .05). Children who underwent RTx, compared with those who underwent LTx or control individuals, had thicker mean IMT at the 6 sites measured (mean [SD], 0.57 [0.07], 0.51 [0.05], and 0.53 [0.06] mm, respectively; P = .02]. As a result of linear regression in renal recipients, variability of glomerular filtration rate (<60 mL/min/1.73 m² vs normal) accounted for 43.3% of variability of the mean of maximal IMT (B = 8.9; SE = 3.1; P = .01). Variability of pre-RTx serum triglyceride concentration (B = 1.6; SE = 0.6; P = .03) and actual triglyceride concentration (B = 10.3; SE = 2.2; P = .002) accounted for 82.2% of variability of maximal IMT. Our findings support previous data on the importance of maintenance of good graft function with sufficient but not overly efficient immunosuppression after transplantation in prevention of future cardiovascular disease.     

Ketoacidosis at the diagnosis of type 1 (insulin dependent) diabetes mellitus is related to poor residual beta cell function. Childhood Diabetes in Finland Study Group

The determinants of the degree of metabolic decompensation at the diagnosis of type 1 (insulin dependent) diabetes mellitus (IDDM) and the possible role of diabetic ketoacidosis in the preservation and recovery of residual beta cell function were examined in 745 Finnish children and adolescents. Children younger than 2 years or older than 10 years of age were found to be more susceptible to diabetic ketoacidosis than children between 2 and 10 years of age (< 2 years: 53.3%; 2-10 years: 16.9%; > 10 years: 33.3%). Children from families with poor parental educational level had ketoacidosis more often than those from families with high parental educational level (24.4% v 16.9%). A serum C peptide concentration of 0.10 nmol/l or more was associated with a favourable metabolic situation. Low serum C peptide concentrations, high requirement of exogenous insulin, low prevalence of remission, and high glycated haemoglobin concentrations were observed during the follow up in the group of probands having diabetic ketoacidosis at the diagnosis of IDDM. Thus diabetic ketoacidosis at diagnosis is related to a decreased capacity for beta cell recovery after the clinical manifestation of IDDM in children.