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.     

Targeted IL‐4 therapy synergizes with dexamethasone to induce a state of tolerance by promoting Treg cells and macrophages in mice with arthritis

F8‐IL‐4 is a recently developed immunocytokine that delivers IL‐4 to sites of inflammation by targeting the neovasculature. We previously reported that F8‐IL‐4, in combination with dexamethasone (DXM), provides a durable therapy in mice with collagen‐induced arthritis (CIA). Therefore, the objective of this study was to identify the mechanism by which IL‐4 and DXM combination therapy provides long‐lasting disease remission. F8‐IL‐4 alone attenuated inflammation in CIA and this was associated with increased T_H2 and decreased T_H17 cell numbers in the joints. Similarly, DXM alone had an antiinflammatory effect associated with lower T_H17 cell numbers. In both cases, these therapeutic benefits were reversed once treatment was stopped. On the other hand, combination therapy with F8‐IL‐4 plus DXM led to a synergistic increase in the percentage of regulatory T (Treg) cells and antiinflammatory macrophages in the arthritic joint and spleen as well as IL‐10 levels in serum and spleen. The net result of this was a more pronounced attenuation of inflammation and, more importantly, protection from arthritis relapse post therapy retraction. In conclusion, F8‐IL‐4 plus DXM is a durable treatment for arthritis that acts by promoting Treg cells in a synergistic manner, and by producing a sustained increase in antiinflammatory macrophages.     

Effect of extracorporeal shock wave therapy on osteoblastlike cells

Extracorporeal shock wave therapy has been used increasingly in musculoskeletal disorders although its biologic mechanisms are not understood completely. The current study evaluated the effects of extracorporeal shock wave therapy on human osteoblastlike cells by using an electrohydraulic shock wave generator and comparing three energy levels. (Group A, 14 kV and 0.15 mJ/mm2; Group B, 21 kV and 0.31 mJ/mm2; Group C, 28 kV and 0.40 mJ/mm2; Control Group, no energy) and two total impulses (500, 1000) for each level. At the end of treatment, a reduction by approximately 76% was observed in Group C cell number versus basal value when compared with the other groups. Viability, biochemical activity, and gene expression of cultured cells were evaluated 24 and 48 hours after treatment. The viability test showed a decrease in Group C viability of approximately 54% at both culture times as compared with the other groups. Significant increases in nitric oxide, osteocalcin, and transforming growth factor-beta1 production ranging from 10% to 35% were found in Group A. All treated groups had lower C-terminal procollagen Type I values than the Control Group, but important increases were observed between 24 and 48 hours in all groups except Group C. This particular finding reveals that osteoblast differentiation in Group A is enhanced strongly during the first 24 hours after exposure leading after another 24 hours to an increase in C-terminal procollagen Type I production and consequently in bone matrix deposition. The current study showed that one of the most important aspects to be considered is not the total number of impulses used, but the energy level of the shock waves, therefore confirming that extracorporeal shock wave therapy has a dose-dependent initial destructive effect on cells when the selected energy is higher than 21 kV.     

Exposure to Sublethal Concentrations of Copper Changes Biochemistry Parameters in Silver Catfish,Rhamdia quelen,Quoy & Gaimard

The effects of Cu exposure on catalase (CAT) and acetylcholinesterase (AChE) activity, formation of thiobarbituric acid-reactive species (TBARS) and metabolic parameters were evaluated in silver catfish (Rhamdia quelen). The fish were exposed for 45 days to 0, 16 and 29 μg/L Cu. The fish that were exposed to Cu exhibited lower TBARS levels in the muscle and higher TBARS levels in the liver. They also showed lower CAT activity in the liver and lower AChE activity in the brain and muscle. Higher glucose and lactate and lower protein plasma levels were observed in the fish exposed to Cu. The changes in the hepatic metabolic parameters were Cu concentration dependent. In the muscle, lower glycogen and higher lactate levels were observed in the fish exposed to Cu. Alterations in the metabolic parameters showed a preference for the anaerobic pathway of energy production and liver protein catabolism to supply the energy demand.     

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.     

Aortic aneurysm complicating bacterial endocarditis in childhood

Bacterial endocarditis is an uncommon diagnosis in childhood with significant morbidity and mortality. Aortic aneurysm as a complication is well described in adults but there are few reports in the paediatric literature. Two children with bacterial endocarditis are described, whose illnesses were complicated by aortic aneurysm formation requiring surgical intervention.     

Role of bacterial translocation in necrotizing enterocolitis

The intestinal mucosa functions as a major local defense barrier preventing bacteria that colonize the gut from invading organs and tissues. Under certain circumstances, bacteria colonizing the gastrointestinal tract can cross the gut mucosal barrier to infect the mesenteric lymph node and systemic organs via a process termed bacterial translocation. Factors that promote the translocation of bacteria or endotoxin from the gut include bacterial overgrowth with gram-negative enteric bacilli, impaired host immune defenses and injury to the gut mucosa resulting in increased intestinal permeability. These same promoting factors are present in patients at increased risk of developing necrotizing enterocolitis. Consequently, this review focuses on the potential role of bacterial and endotoxin translocation from the gut in the pathogenesis of necrotizing enterocolitis.     

Malnutrition as a prognostic factor in lymphoblastic leukaemia: a multivariate analysis

One hundred and twenty eight Brazilian children with lymphoblastic leukaemia were intensively treated with a Berlin-Frankfurt-Munich based protocol. More children had a white cell count above 50 x 10(9)/l (31%) then observed in developed countries. After a median follow up of 31 months (11-58 months), the estimated probability of relapse free survival was 41% (7%) for the whole group. After adjustment in the Cox's multivariate model, malnutrition was the most significant adverse factor affecting duration of complete remission. Age above 8 years and high peripheral white cell count were also significant adverse factors. Among the nutritional indices, the height for age and weight for age z scores were both significant, whether the cut off points of z-2 or z = -1.28 were chosen to define malnutrition. A strong statistical association between the two indices was found; the contribution of height for age z score to the prediction of relapse free survival was more significant. Children with height for age z score < -2 had a relapse risk of 8.2 (95% confidence interval 3.1 to 21.9) relative to children with z score > -2. The results of this study suggest that socioeconomic and nutritional factors should be considered in the prognostic evaluation of children with leukaemia in developing countries.