Class III malocclusions in deciduous or early mixed dentition: an early orthopaedic treatment.

BACKGROUND: An early approach to Class III malocclusions is crucial. From diagnosis to treatment, the aim is be to correct and harmonise maxillary and mandibular growth as quickly as possible. CASE REPORT: A new treatment protocol for the early treatment of Class III malocclusions to be used in children in deciduous teething and/or early mixed teething was proposed. Ten children, 6 females and 4 males, with an overall average age of 6.5 years (6 years and 6 months) at time T0 were included in this experimental study. Twelve months orthopaedic interceptive therapy using two protraction facemasks (Delaire and Petit mask) and two types of extraoral elastic bands (8 and 16 oz) were given. Parents/guardians were involved as much as possible to increase compliance with the treatment. CONCLUSION: The orthopaedic-interceptive treatment for Class III malocclusion intends to provide a potential improvement of the growth response so that significant results can be achieved quickly. The motivational role of the parent can positively influence the child's treatment cooperation. The clinician should then try to make parents understand the importance of early treatment of Class III malocclusion thus obtaining a full cooperation with the parent/ guardian and a good compliance from the child.

Myofunctional therapy Part 3: Tongue function and breastfeeding as precursor of oronasal functions.

Breastfeeding is the best practice to ensure proper nutrition, correct growth of the craniofacial complex and overall health of the baby with optimal breathing, feeding and sleeping functions. Many mothers face breastfeeding problems due to the baby's difficulty in latching, especially if the lingual frenum is restricted. Early detection and understanding of some of the root causes of those difficulties will lead to an early intervention, thus getting the babies on the right tract of their full potential of growth and development.

Eicosapentaenoic acid pre-treatment reduces biochemical changes induced in total brain and myelin of weanling Wistar rats by cuprizone feeding.

Recently, we investigated the effects of eicosapentaenoic acid (EPA), a fatty acid which modulates immune response and stimulates myelin gene expression, in an established model of multiple sclerosis (MS): the experimental autoimmune encephalomyelitis (EAE) induced in Dark Agouti rats. As scientific evidences and our previous studies have suggested that EPA could directly affect oligodendrocytes, we have now evaluated the effects of EPA in the non-immune mediate MS model characterized by selective oligodendrocytes damage induced by cuprizone (CPZ). We found that feeding weanling rats diets containing 0.6% CPZ for 2 weeks induced variation of whole brain and myelin biochemical composition representative of a severe myelin damage. We thus administered daily and by gavage EPA or PBS to 2-day old rats up to 21 days. Afterwards, rats were fed CPZ diet for 9 days. The results show that compared to PBS/CPZ fed rats, the whole brain cerebroside content in EPA pre-treated rats was statistically increased as well as there was an overall trend of increase of all other biochemical components.

Effect of micronutrient-enriched sunflower oils on plasma lipid profile and antioxidant status in high-fat-fed rats.

The main objective of this study was to evaluate in vivo whether micronutrient-enriched high-oleic sunflower oils (optimized oils) obtained using different crushing and refining procedures could have any beneficial effect on plasma lipid profile and antioxidant status. Sprague-Dawley rats were fed a high-fat diet for 4 weeks. The lipid source consisted of 20% optimized sunflower oils with different quantities and qualities of micronutrients. The control group received traditional refined high-oleic sunflower oil. The experimental optimized oils in the diets had a hypolipidemic effect. The reduction in plasma triglyceride and total cholesterol levels was 43% and 20%, respectively, in the group fed the diet with the highest levels of micronutrients. The serum ferric antioxidant capacity, superoxide dismutase, glutathione peroxidase and reduced glutathione significantly increased and lipid peroxidation decreased in parallel with the enhancement of micronutrients. These results suggest that a regular intake of optimized sunflower oils can help to improve lipid status and reduce lipid peroxidation in plasma.

Polyunsaturated fatty acids and neurological diseases.

This review summarizes the knowledge of the role of dietary PUFAs, especially omega-3, on normal brain function. Furthermore, it reports the evidence pointing to potential mechanisms of omega-3 fatty acids in development of neurological disorders and efficacy of their supplementation in terms of symptom management.

Lipopolysaccharide downregulates fatty acid amide hydrolase expression and increases anandamide levels in human peripheral lymphocytes.

Lipopolysaccharide (LPS) increases the levels of the endogenous cannabinoid anandamide (N-arachidonoylethanolamine, AEA) in rat macrophages, but the mechanism responsible for this effect has not been elucidated. Here we demonstrate that LPS enhances the levels of AEA (fourfold over controls) also in human lymphocytes. We show that in these cells LPS inhibits the activity of the AEA-degrading enzyme fatty acid amide hydrolase (FAAH), by downregulating the gene expression at transcriptional level. Lymphocytes have also a specific AEA transporter and a functional CB1 cannabinoid receptor, which were not modulated by LPS. The effect of this endotoxin on FAAH was not mediated by AEA-induced activation of cannabinoid receptors. Conversely, the stimulatory action of LPS on AEA levels might be due to inhibition of FAAH, as suggested by the observation that an increase of AEA amounts was also induced by an irreversible FAAH inhibitor. These results suggest that lymphocytes take part in regulating the peripheral endocannabinoid system and endocannabinoid homeostasis.

Th 1 cytokine production by peripheral blood mononuclear cells in X-linked adrenoleukodystrophy.

Cerebral adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN) are the two most frequent clinical phenotypes of the same genetic defect leading to the accumulation of very long chain fatty acids (VLCFA). Previous studies have suggested that inflammatory cytokines may play a role in the cerebral demyelination and in phenotype expression of the disease. We analyzed cytokine production by stimulated peripheral blood mononuclear cells (PBMC) from 17 patients (four asymptomatic subjects, eight AMN and five ALD). Our results show that lipopolysaccarides (LPS) stimulated PBMC from both symptomatic and asymptomatic patients have an increased production of IL-12 and TNFalpha compared to controls, while after phitoemoagglutinin (PHA) stimulation we observed a decreased production of IL-6 and IL-10. These data indicate that, following an immunological stimulus, PBMC from patients have an increased production of cytokines typical of a Th1 cell response which is able to promote the inflammatory process. This characteristic profile of cytokine production could be related to the biochemical defect and could have a role in central nervous system (CNS) pathogenesis.

Diet, lipids and brain development.

Brain development is a sequential anatomical process characterised by specific well-defined stages of growth and maturation. One of the fundamental and necessary events in the normal development of the central nervous system in vertebrates is the formation of a myelin sheath. It is becoming more evident that this process is influenced by dietary lipids. A number of findings have indicated that the administration of a diet deficient in essential fatty acids during development causes hypomyelination in the rat brain. Our studies have shown that lipids can also play a role in accelerating myelinogenesis in the brain of rats whose mothers had been fed, during pregnancy and lactation, a lipid fraction extracted from yeast grown on n-alkanes. Further studies have shown that accelerated myelinogenesis is connected to a precocious appearance of behavioural reflexes. Thus, the use of particular lipids in human nutrition must be carefully screened for possible effects on brain development.

Anandamide and 2-arachidonoylglycerol inhibit fatty acid amide hydrolase by activating the lipoxygenase pathway of the arachidonate cascade.

Treatment of intact human neuroblastoma CHP100 cells with anandamide (arachidonoylethanolamide, AEA) or 2-arachidonoylglycerol (2-AG) inhibits intracellular fatty acid amide hydrolase (FAAH). This effect was not associated with covalent modifications of FAAH, since specific inhibitors of farnesyltransferase, kinases, phosphatases, glycosyltransferase or nitric oxide synthase were ineffective. Electrophoretic analysis of (33)P-labelled proteins, Western blot with anti-phosphotyrosine antibodies, and glycan analysis of cellular proteins confirmed the absence of covalent modifications of FAAH. The inhibition by AEA was paralleled by an increased arachidonate release, which was not observed upon treatment of cells with linoleoylethanolamide, palmitoylethanolamide, or oleoylethanolamide. Moreover, cell treatment with AEA or 2-AG increased the activity of cyclooxygenase and 5-lipoxygenase, and the hydro(pero)xides generated from arachidonate by lipoxygenase were shown to inhibit FAAH, with inhibition constants in the low micromolar range. Consistently, inhibitors of 5-lipoxygenase, but not those of cyclooxygenase, significantly counteracted the inhibition of FAAH by AEA or 2-AG.

Susceptibility to oxidation of plasma low-density lipoprotein in X-linked adrenoleukodystrophy: effects of simvastatin treatment.

This paper shows for the first time the higher oxidizability of low-density lipoprotein (LDL) in plasma from adrenoleukodystrophy (ALD) patients compared to that of control subjects. LDL oxidation susceptibility was assessed by conjugate diene formation, hydroperoxide and lipoperoxide formation, and electrophoretic mobility. Simvastatin therapy, an HMG-CoA reductase inhibitor, seems to be a protective pharmacological agent against the higher oxidizability of LDL in plasma from ALD patients.

The Myelinogenesis Process in Undernourished Rats Rehabilitated with Different Dietary Lipids.

Our previous studies have indicated that pups born from mothers fed lipids obtained from yeast (Candida lypolitica) grown on n-alkanes during pregnancy and lactation show an acceleration of myelinogenesis. In the present work we carried out experiments using an undernutrition model to establish if such microbial lipids can also play a role in accelerating the myelin process in hypomyelinated rats. This model was produced by restricting maternal dietary intake during the last 4 days of pregnancy and the lactating period. Diet-restricted dams were divided into 3 groups when pups were 14 days old. The first group was switched to ad libitum diet containing 9% margarine and 1% corn oil, the second to ad libitum feeding diet containing 10% of microbial lipids and the third to ad libitum feeding standard diet containing 3% of lipids. The offspring were sacrificed at differing days of nutritional rehabilitation. The recovery of the body and brain weight was slower in rats fed 3% of lipids than animals maintained on 10% of lipids. The test group showed an earlier increase both in the relative levels of proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) mRNAs and in the 2'-3'-cyclic nucleotide 3' phosphohydrolase (CNPase) activity compared with the other two groups. These results indicate that the reversal of myelin delay would seem to be accelerated in the group fed microbial lipids.

Thymectomy and multiple sclerosis: ultrastructural study of an experimental model.

Transmission electron microscopy was performed on specimens of the thymus of rats induced for acute experimental allergic encephalomyelitis (EAE). The ultrastructural alterations of the thymus were progressive and correlated with EAE development. The thymic disorganization was due to a progressive degeneration of both epithelial cells and thymocytes. These data suggest a direct involvement of the epithelial thymic cells and thymocytes in EAE pathogenesis and may suggest the intriguing therapeutic concept of thymectomy in the management of multiple sclerosis.

[Adrenoleukodystrophy: genetics, phenotypes, pathogenesis, and treatment]. / Adrenoleucodistrofia: genetica, fenotipi, patogenesi e trattamento.

Adrenoleukodystrophy is a genetically determined disorder inherited as an X-linked recessive trait due to the defective peroxisomal oxydation of very long chain fatty acids (VLCFA). It is hallmarked by demyelination of the central nervous system and adrenal insufficiency. Even though the studies concerning the molecular basis of the disease are in progress, the role of VLCFA in the demyelination is still unclear. In this paper we report the most recent knowledges about genetics, pathogenesis and treatment of this disorder. 117 cases have been recognized in Italy in the period 1985-1997, but many cases could be missing due to the heterogeneus clinical manifestations that vary from mild to very severe forms. To control the devastating course of this disease two therapeutic approaches are under evaluation: bone marrow transplantation and dietary treatment based on a mixture of glyceroyl trioleate and glyceroyl trierucate. Nevertheless this dietary treatment provides normalization of plasma VLCFA, no significant modification of the natural course of the disease has been demonstrated. For what concerns bone marrow transplantation, in recent years a more accurate selection of patients and donors has been giving favourable results, but some strict criteria should be respected.

X-linked adrenoleukodystrophy: first report of the Italian Study Group.

In this paper we report Italian data on X-linked adrenoleukodystrophy (ALD) collected from 1985 to 1997. This disease appears to be the most common of the peroxisomal disorders and is associated with a functional defect of the peroxisomal very long chain fatty acid (VLCFA) oxidation. In Italy 117 cases have been recognized, but many cases may be unrecognized due to the heterogeneous clinical manifestations that vary from mild to very severe forms. To control the devastating course of this disease two therapeutic approaches are under evaluation: bone marrow transplantation (BMT) and dietary treatment based on a mixture of glyceroyl trioleate (GTO) and glyceroyl trierucate (GTE). Our experience of 68 subjects submitted to dietary treatment shows that almost all patients with signs of cerebral involvement at the beginning of treatment worsened or died, patients with the milder form, adrenomyeloneuropathy (AMN), remained stable, while 4 of the 15 presymptomatic subjects developed neurological signs of the disease. In recent years a more accurate selection of patients and donors for BMT has given favourable results, but some strict criteria should be respected.

Effects of exogenous hexacosanoic acid on biochemical myelin composition in weaning and post-weaning rats.

X-linked Adrenoleukodistrophy (ALD) is characterized by an increase of very long chain fatty acids (VLCFA) in particular of hexacosanoic acid (HA), in tissues and fluids. The biochemical abnormality is due to the dysfunction of peroxisomal degradation of VLCFA. To-date it is unclear if the demyelination which characterizes this disease is the direct consequence of HA accumulation. In order to investigate whether the large amounts of exogenous HA could affect myelin synthesis, 500 micrograms of this fatty acid dissolved in peanut oil were administered daily and by gavage to newborn rats. Since myelin is actively synthesized during early neonatal life and it can be altered by environmental factors including diet, we analyzed lipid and protein composition of myelin after 20, 30 and 60 days of HA administration. Our results show that exogenous HA is incorporated in myelin where it determines biochemical alterations in normal rats having a functioning peroxisomal system. Even though the differences between controls and treated rats are slight, we observed in test rats, a decrease of 2'3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) activity and of myelin basic protein (MBP) content at any time studied. The decrease of glycolipids (GL) was present only after 20 days of treatment. Since these parameters are related to myelin development, our data lead us to think that the myelin of the treated animals is less mature than that of controls.

Exogenous lipids in myelination and myelination.

Myelinogenesis is a scheduled process that depends on both the intrinsic properties of the cell and extracellular signals. In rat brain, myelin development is an essentially postnatal event and environmental interferences could affect myelin synthesis. Nutrition plays an important role, since severe postnatal malnutrition and essential fatty acid (EFA) deficiency cause hypomyelination. Even though the dietary effects are more pronounced in the postnatal period, dietary lipids can affects myelin development also in the postweaning period. Rats fed with diets rich in polyunsaturated n3 fatty acids showed a decrease of the relative amount of myelin basic protein (MBP) and a CNPase activity indicating a delay in myelin deposition and/or an instability of its structure. Our recent studies have shown that dietary fatty acids can be positively involved in the control of central nervous system (CNS) myelinogenesis. Offspring of rats fed diets containing odd chain fatty acid during pregnancy and lactation show an early development of behavioral reflexes linked to myelination compared to controls fed a diet containing margarine. Subsequent studies have shown that the expression of myelin proteins is higher in test than in control animals, but the mechanism of the action of fatty acids is still unknown. Also human brain myelinogenesis can be affected by environmental factors. EFA deficiency has been well studied for the important role of C22:6 (a C18:3 metabolite) in the vision system development. The observation that dietary fatty acids can affect membrane composition has led to the use of modified diets in some CNS pathological conditions. For example, preterm infants characterized by low levels of C22:6 and fed with formulae diets enriched in this fatty acid, show a recovery of visual function. The administration of C22:6 has also been tested in patients affected by peroxisomal biogenesis disorders which are associated with very low levels of this fatty acid in the brain. During the treatment, C22:6 content increases in red blood cells, and probably in the brain membranes, as considerable neurologic and electrophysiological improvement suggest. A mixture of glyceryltrierucate and glyceryltrioleate has been tested in the demyelinating disease Adrenoleukodistrophy which is characterized by an abnormal accumulation of very long chain fatty acids (VLCFA) in tissues and fluids. The diet is able to lower VLCFA levels in plasma, but its efficacy for myelin damage is debated. Lastly, a diet which reduces the intake of saturated fatty acid and increases the quantity of polyunsaturates is suggested for multiple sclerosis patients since a decrease of linoleic acid in their plasma and erythrocytes has been observed. Such a diet seems able to reduce the severity of the attacks.

Accelerated myelinogenesis by dietary lipids in rat brain.

Our previous work showed an early development of behavioral reflexes in rats whose mothers had been fed, during pregnancy and lactation, a lipid fraction extracted from yeast grown on n-alkanes (which contain 50% odd-chain fatty acids) in comparison with controls fed a margarine diet. To clarify whether the observed changes might be linked to an early myelination, we have investigated mRNAs involved in myelin synthesis in the brains of offspring at 5 days of age by northern blot and in situ hybridization. Northern blot analysis showed that proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) mRNAs were higher in animals on the lipid diet compared with controls. In situ hybridization with probes specific for PLP, myelin basic protein, and MOG mRNA showed significantly higher numbers of positive cells in test animals compared with controls in all brain regions. This study shows an acceleration of myelinogenesis induced by dietary lipids. These data can give a new insight in the therapeutical approaches involved to promote repair in demyelinating diseases.

Influences of hypothyroidism on lipid composition and inositol lipid-linked receptors responsiveness and protein kinase C (PKC) activity in the cerebral cortex of Lewis rats.

The influence of hypothyroidism (HO) induced by treatment with propylthiouracil on lipid composition, receptor responsiveness of M1-muscarinic receptors (M1AChRs) and metabotropic glutamate receptors (mGluRs) as well as on protein kinase C (PKC) activity was investigated in the cerebral cortex of Lewis rats. HO did not influence the lipid composition. There was a significant 2-fold increase of efficacy and 6-fold decrease of potency of carbachol-induced inositol phosphate (IP) accumulation in HO, with respect to control rats. The efficacy of trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD)-induced IP accumulation was also higher in HO (by 50%), without differences in EC50 values. The activities of soluble calcium-dependent and calcium-independent PKC were higher in HO than in control rats (both roughly 30%); membrane-associated PKCs were not modified. The data indicate that HO induces an increased responsiveness of M1AChRs and mGluRs and a rise in the soluble PKC activity that could be available and ready for translocation.

High dose immunoglobulin IV treatment in adrenoleukodystrophy.

X-linked adrenoleukodystrophy (ALD) is an inborn error of peroxisomal metabolism characterised by progressive demyelination of the central nervous system and by hypoadrenalism. The biochemical defect of ALD results in an impairment in degradation of very long chain fatty acids (VLCFA) with their accumulation in plasma and tissues. Many therapeutic approaches have been tried. Recently, a restricted diet and glycerol trioleate/erucic (GTOE) supplementation have shown normalisation of VLCFA plasma levels, although they are not effective in altering the clinical course of X-linked ALD. The preliminary results are presented of a twelve month trial of immunomodulation by intravenous high-dose immunoglobulins in six patients, mean (SD) age 10.48 (2.8) affected by X-linked ALD, on VLCFA restricted diet plus GTOE supplementation therapy. Six patients aged 9.30 (1.5) with similar clinical characteristics and on the same restricted VLCFA regime of GTO/GTE therapy were studied as the control group. After two months VLCFA levels fell to normal values and remained so for all patients throughout the study. These data show that immunoglobulins are not able to arrest the progression of the disease. The MRI and clinical symptoms deteriorated to the same extent in both groups.