For example, an impressive study carried out by Nir Barzilai’s gr

For example, an impressive study carried out by Nir Barzilai’s group showed that removal of white adipose tissues (WAT)

from rats can mimic the positive effects of DR, suggesting that WAT might mediate the DR response, or that DR regulates WAT.14 However, although DR-increased lifespan was discovered over 80 years ago, the detailed mechanisms underlying DR effects are still elusive. Sir2 and its homologue sirtuins became more attractive to the global aging community when a series of publications demonstrated that sirtuins are pivotal in the regulation of longevity in lower metazoans. Similar to the findings in the yeast Saccharomyces cerevisiae, increasing the Inhibitors,research,lifescience,medical AVL-301 research buy activity of sirtuins from Caenorhabditis elegans15 and Drosophila melanogaster,16 using either genetic17 or chemical means,18 also extends their lifespan by at least 15%. Inhibitors,research,lifescience,medical Therefore, it was suggested that the role of sirtuins in regulating lifespan is evolutionarily conserved, and understanding its regulation at the molecular level thus has great therapeutic opportunities. How are sirtuins regulated? To date we know of multiple layers of sirtuin regulation. Initially, an intense debate took place on this matter. At first, it was suggested that NAD+ levels regulate yeast Sir2 activity.19 However, in Inhibitors,research,lifescience,medical yeast, exact measurements showed that cellular

concentrations of NAD+ are around 4 mM. Thus, given that the Km of Sir2 for NAD+ is around 50 μM, a 10-fold change in NAD+ concentration was required to

affect Sir2 activity.20 Therefore, the Sinclair group suggested Inhibitors,research,lifescience,medical that sirtuin activity is regulated by nicotinamide (NAM), one of the products of its NAD+ dependent deacetylase enzymatic activity.21 On the other hand, it was recognized that fluctuations in NAD levels cannot provide a reasonable model for sirtuin regulation, and the Guarente group suggested that NADH, Inhibitors,research,lifescience,medical which exists in the micromolar range in the cell, inhibits Sir2 enzymatic activity.22 A recent study showed that yeast Sir2 activity can be regulated by both NADH and NAM: With high DR (0.1% glucose), clearance of NAM regulates Sir2 activity, whereas with low DR (0.5% glucose) a reduced NADH/NAD ratio regulates Sir2 activity.23 What controls endogenous NAM levels? In yeast, PNC1 enzyme converts NAM, a sirtuin inhibitor, into nicotinic acid (NA), which does not inhibit Sir2. This NA is later used by the NAD salvage ADP ribosylation factor pathway to generate NAD+. A sophisticated study by Anderson et al. demonstrates that PNC1 levels are regulated by nutrient availability.21 Under DR conditions, PNC1 levels and activity increase, resulting in increased Sir2 activity. This model was expanded for other mild stressed conditions such as increased osmolarity and heat, in which PNC1-dependent clearance of NAM under various stresses increases yeast lifespan via Sir2 up-regulation.

In an effort to better understand utility, some authors have reco

In an effort to better understand utility, some authors have reconceptualized dichotomous outcomes (eg, the proportion of I-BET-762 order patients who improved their ADASc scores by 4 or more, or the proportion of patients who do not worsen their ADASc scores by 4 or more compared with placebo) as a “number needed to treaf” (NNT) statistic (eg, see reference 46). This Inhibitors,research,lifescience,medical statistic, the inverse of the absolute risk difference,

proposes to quantify the number of patients needing to be treated in order for 1 patient, to show benefit. Generally, among these analyses, the NNT might, range between 3 and 20, albeit, with wide confidence intervals. Unfortunately, the NNT statistics do not address how physicians, patients, caregivers, and health authorities value clinical outcomes Inhibitors,research,lifescience,medical such as differences on cognitive scores or global ratings, and certainly do not address whether improvement over the course of 6 months

is sufficient or meaningful therapy in a relentlessly progressive illness with a chronic course over several years. Another effort to assist clinical relevance is contained in the rivastigmine EMEA prescribing information. There, the EMEA looked specifically at a subgroup of patients who both improved Inhibitors,research,lifescience,medical on the ADASc by 4 points or more and did not worsen on both global ratings and activities of daily living. By restricting the outcomes to people who benefited in three domains of functioning, the EMEA hoped to get a more specific estimate Inhibitors,research,lifescience,medical of the actual numbers of patients who benefited cognitively, clinically, and functionally. In this analysis, the proportion of responders was 10% vs 6% for higher-dose rivastigmine (6-12 mg/d) compared with placebo. Clinical utility is a balance between efficacy, safety, and tolerance. To date, no effectiveness trials have been conducted, nor have there been trials directly comparing one ChEI with another

in typical, Inhibitors,research,lifescience,medical ordinary AD patient populations. These kinds of trials are urgently needed. Duration of efficacy and long-term efficacy The randomized clinical trials are nearly all of 6 months’ duration. One donepezil trial suggested that it took 3 months after discontinuation for patients to return to the placebo group’s Ketanserin level of function, while another trial showed that donepezil was effective for 12 months (although many patients did not complete). Thus, the empirical evidence is that ChEIs – and donepezil in particular – may stabilize or improve cognitive symptoms for 6 to 12 months compared with a contemporaneous placebo-treated group. Claims regarding long-term treatment and efficacy come from largely uncontrolled and always observational studies of patients who have survived the 6-month acute treatment trial.

In the present study, CR was observed in 4 patients (11%) and tot

In the present study, CR was observed in 4 patients (11%) and total response rate was high, representing a satisfactory result. In particular, patients with CR showed a long period of CR and long overall survival. In patients receiving systemic chemotherapy, the rate of achieving CR is supposed to be low at this stage (33). The power

of local control with HAIC thus appears promising. Kemeny et al. reported on the CALGB9481 test, as a randomized prospective trial between Inhibitors,research,lifescience,medical groups receiving HAIC with FUDR and leucovorin compared to systemic chemotherapy with 5-FU and leucovorin (34). Their results showed a significantly longer median survival (24.4 months), longer progression-free survival (9.8 months), Inhibitors,research,lifescience,medical and higher response rate (47%) with HAIC in comparison with systemic chemotherapy. The present results were similar to those described by Kemeny et al., albeit with a higher response rate of 64% (34). This might be attributable to different regimens of chemotherapy. In comparison with the latest systemic chemotherapy, survival and

response rate in our results were not Inhibitors,research,lifescience,medical unfavourable (18,22,33). Although catheter-related problems were emphasized in previous results (29,30) and we also encountered 6 cases with catheter-related complication, HAIC was able to be maintained in 4 cases with replacement of a port or catheter. In comparison with the report by Inhibitors,research,lifescience,medical Kerr et al. (30), the complication rate was low and management was better in our study. When the management of ports and catheters for HAIC was well-organized, the scheduled cycle of administration of HAIC would be achievable in many cases. In terms of severe chemotherapy-related

toxicity, we encountered only 2 patients. Inhibitors,research,lifescience,medical The drug toxicity of HAIC is lower than that of FOLFOX, FOLFIRI or use of molecular-targeted drugs (35). In non-CR cases, tumors eventually progressed and patients died within 4 years. Integrase inhibitor resistance testing Furthermore, CLM with extrahepatic metastases showed very poor prognosis. Additional methods to obtain longer survival are thus necessary in such cases. We Adenosine attempted combination therapy with HAIC and systemic chemotherapy to improve survival in non-CR cases. As HAIC was relatively inexpensive and showed fewer severe side effects compared to FOLFOX or FOLFIRI in our results, the significance of HAIC for controlling liver metastases remains. By combining systemic chemotherapy with HAIC, a well-balanced regime for better quality results may be achieved. Kemeny et al. reported the significance of HAIC with systemic chemotherapy for non-resectable CLM, in combination with oxaliplatin/CPT-11/FUDR. The response rate reached high as 90%, and median survival was long, at 36 months as bove (36). Ducreux et al.

While dermal fibroblasts adhere within 4 hours, NCP took at least

While dermal fibroblasts adhere within 4 hours, NCP took at least 3 days to adhere and to spread on the substrate. For this reason, the spinner culture was carried by using a cycle of 10 minutes at rest and 40 minutes at 30 rpm for up to 3 days of culture. After this time, the dynamic culture switched to continuous stirring at the velocity of 30 rpm up to 9 days of culture. During the culture time, NCP was able to

adhere to and colonize the microbeads, recreating a structure quite similar to that of native muscle, composed by cardiomyocytes and fibroblast embedded in a collagen network as shown in Figure 3A. CME showed uniform cell distribution and important Inhibitors,research,lifescience,medical biological structure such as sarcomere actin filaments; connexin-43 junctions were also present. One of the most important features of CME is the self-beating capability generated Inhibitors,research,lifescience,medical by the spontaneous

beat of the cardiomyocytes fraction present in the tissue equivalent. After 4 days of culture, cardiac microtissues were collected from the spinner culture, and their spontaneous contraction was monitored by video microscopy. The tissue Inhibitors,research,lifescience,medical organization continued till the end of the culture, and at each time point, beating and contracting microcardiac muscle was observed with a beating rate of 45 bpm (Figure 3B). Interestingly, when placed in close proximity, two micro CMEs having different beating frequencies were able to synchronize after 40 minutes. After 1 day, the CMEs underwent a fusion process, and the resulting tissue was made by a microtissue with a single beating frequency. Figure 3 Masson trichrome of micro CME; (B) beating properties Inhibitors,research,lifescience,medical of the micro CME; the peak represents a single beat. The translation of a microscaffold-based bottom-up strategy from dermis to cardiac muscle tissue fabrication resulted in a promising strategy for heart tissue engineering. Despite other Inhibitors,research,lifescience,medical techniques such as cell sheet or cellular find more spheroids, the presence of the microscaffold aids tissue reorganization and ECM synthesis, simultaneously representing a structure that guarantees mechanical support. The presence of the scaffold does not hinder the electromechanical properties of the CME, which showed spontaneous beating

and synchronization properties. This indicates that the CME can be used as an implantable living microtissue for infracted zone regeneration. Conclusion below The strategy presented in this work highlights the production of functional tissue in vitro, made up of endogenous ECM and tunable in size and shape. In light of this, the tissues created could be useful in regenerative medicine as they could be injected as living microtissues in damaged sites or, if assembled in large 3D tissues, could be used as a patch for extended damages. The versatility of this technology paves the way for in vitro biofabrication of several kinds of tissues, leading to an increased availability of “living” tissue or organ substitutes. Funding Statement Funding/Support: The authors have no funding disclosures.

Even more important, particularly after crossing more than five t

Even more important, particularly after crossing more than five time zones, is avoiding sunlight exposure at the wrong time, which will shift circadian rhythms in the direction opposite to that traveled. When flying from Los Angeles to Madrid, for example, it would take several more days to delay the body clock 15 h than to advance it 9 h. (However, extreme night owls might prefer to delay their clocks no matter which direction of travel.) Precise recommendations for obtaining and avoiding sunlight at destination depend on what are thought to be the light PRC’s

break points. The following recommendations are based on a light PRC with the break points at CT 6 and CT 18, using Inhibitors,research,lifescience,medical the beginning of the light pulse as its phase reference. Using the middle of a relatively long bout of bright light exposure as the phase reference, which is done in most human (but not animal) studies, would put these break Inhibitors,research,lifescience,medical points a few hours later; however, this requires people to schedule long periods of (preferably bright) light exposure. Furthermore, a recent study indicates that the beginning of the light pulse is its most powerful part, at

least with respect to causing phase selleck chemicals advances. After traveling across five or fewer time zones, start sunlight exposure as early as possible in the morning after going east or as late as possible in the afternoon after going west. After traveling Inhibitors,research,lifescience,medical across six or more time zones, obtain sunlight exposure in the middle of the day and avoid it in the morning

after going east or at the end of the day after going west. On subsequent days, these times can be shifted, as if one had traveled through Inhibitors,research,lifescience,medical fewer time zones (see below). Using both light and melatonin at the optimal times, it is reasonable to assume a rate of phase shifting of 3 h per day. For example, after traveling nine time zones to the east, Inhibitors,research,lifescience,medical a person who habitually arises at 7.00 am should avoid sunlight exposure before 10.00 am and obtain at least 30 min of it shortly after this time. The next day sunlight exposure should occur shortly after 7.00 am. Melatonin should be taken at 2.00 pm before travel and at 11.00 pm upon reaching the destination. It should then be taken 3 h earlier each day until it is again taken at 2.00 pm for a couple of days. After traveling nine time zones to the west, take melatonin at 10.00 pm the first night, but on subsequent SPTLC1 nights it should be taken only if awake after 1.00 am and then again upon final awakening in the morning. After traveling six or more time zones to the west, bright light should be avoided at the end of the day and sunlight should be obtained in the middle of the day. After 1 or 2 days, bright light should be obtained at the end of the day. Melatonin can be taken at bedtime the first night at destination, but should not be taken before 1.00 am on subsequent days, except under special circumstances.

As already mentioned, the present approach in psychopharmacology

As already mentioned, the present approach in psychopharmacology is essentially syndromal. For example, antidepressants are drugs aimed at treating depressive symptoms, while antipsychotics are aimed at treating schizophrenic symptoms. Similarly, antihypertensive

drugs are prescribed in internal medicine to treat high blood pressure. However, a major difference is that internists know better than psychiatrists what drugs do at the pharmacological level. Internists know that they either substitute for a missing Inhibitors,research,lifescience,medical compound (eg, insulin), attack an infectious agent (ie, antibiotics), or “cheat the body” (eg, induce a dysfunction in normal physiology in order to influence a symptom). For example, drugs used for cardiac insufficiency decrease blood Dasatinib price volume, increase the muscular Inhibitors,research,lifescience,medical capacity of the myocardium, modify vascular resistance, lower heart rate, etc. Internists have a clear idea of what occurs when a

patient develops cardiac insufficiency. They know that, a diuretic is a regulator of electrolyte homeostasis and so do not call it an “antidyspnea” drug just, because it controls the respiratory difficulties of patients with cardiac insufficiency. In psychopharmacology, direct. Inhibitors,research,lifescience,medical links are often made from receptor or transporter to symptoms, without an intermediate analysis of which physiological functions are modified by the medication. Recent discoveries in the field of antidepressant agents show that extrapolation from the action of SSRIs action on the 5HTT to improvement, in mood is a. gross Inhibitors,research,lifescience,medical simplification. Indeed, several antidepressants also Inhibitors,research,lifescience,medical decrease the expression of corticotropin-relcasin hormone (CRH) in the hypothalamus and increase the expression of glucocorticoid receptors in the hippocampus2; in addition, they increase the expression of gonadorelin (LHRH),3 and of brain-derived neurotrophic factor

(BDNF).4 These pharmacological effects might explain, in part, the clinical effects, through an influence on several brain functions. Psychiatric disorders Diagnoses using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-TV) and the International Statistical Classification of Diseases, 10th Revision Thiamine-diphosphate kinase (ICD-10) manuals are based on qualitative classification: a particular disorder is present if the required number of symptoms is found. Only a few mechanisms have been established for these disorders. The problems of a descriptive classification have long been recognized, as illustrated by the following citation, translated from a French book by Nathan5: “Until a classification can be based on etiology and pathogenesis, it does exist but is theoretically and practically sterile.


Receptor profile and animal TAE684 mouse pharmacology Risperidone has high affinity for the D2 dopamine receptor family and for the 5-HT2A and 5-HT7 receptors. The drug also has high affinity for the α1 and α2 adrenoceptors, but moderate affinity for the 5-HT2C and histamine H1 receptors.18 The major active metabolite of risperidone, 9-OH-risperidone, has the same affinity profile. Thus, the drug has antidopaminergic and antiserotonergic

characteristics in animal models of drug Inhibitors,research,lifescience,medical action, with greater antiserotonergic than antidopaminergic actions. It entirely lacks anticholinergic properties. Risperidone increases dopamine turnover in frontal and olfactory cortex to a greater extent than it docs in striatum.19 Moreover, risperidone only produces catalepsy in rats at high dose levels. Consistent with these behavior actions is the tendency of risperidone to only Inhibitors,research,lifescience,medical activate c-fos mRNA in the ventral, not dorsal striatum. However, the drug produces depolarization blockade in A9 as well as A10 dopamine neurons, without the selectivity shown by clozapine. Preclinically, the animal profile is mixed with respect, to whether or not motor side effects would be predicted in human use. Efficacy in chronic psychoses Risperidone was first, tested in a multicenter, multidosc, international Inhibitors,research,lifescience,medical study in the psychosis of schizophrenia.33 Data from this trial indicated that the drug was surely antipsychotic and

potently so, but that the best dose was in the lower dose range, around 6 mg/day, which was Inhibitors,research,lifescience,medical confirmed in further studies. Current drug use studies suggest that the doses of risperidone currently prescribed are biphasic, with one peak around 2 to 5 mg/day and another peak at doses above 8 mg/day. The lower dose range is not associated with parkinsonism and only low levels of akathisia, whereas the higher

dose range has haloperidol-like levels of motor side effects. Early use with risperidone suggested that the drug might, have some positive effects on cognitive dysfunction in schizophrenia. In Inhibitors,research,lifescience,medical in vivo ligand studies in humans, the occupancy of striatal dopamine receptors remains Ergoloid below 70% within the low dose range, while occupancy of cortical serotonin receptors is higher by about 20%, in the range of 80% to 95%.34 This is characteristic of the second-generation antipsychotics and is consistent with their animal pharmacology. Risperidone was one of the first second-generation antipsychotics with low motor side effects, especially at low dose levels, to also have a good side-effect profile. Hence, the drug was used extensively, and then studied, in the psychosis of the elderly, then an area of great medical need. In an early report,35 risperidone was found to be “safe and effective” for psychosis in the elderly, with hypotension being a use-limiting side effect. Later controlled trials confirmed and extended these early observations.

somnogenic substance that progressively

accumulates with

somnogenic substance that progressively

accumulates with prolonged wakefulness, with adenosine being one of the most cited candidates.7 Both homeostatic and circadian mechanisms are thought, to influence the opposite action of neurons promoting wakefulness and neurons promoting sleep. Wake-active neurons are cholinergic (located in the basal forebrain and in the tegmentum) and monoaminergic (noradrenergic in the locus ceruleus, serotonergic in the dorsal raphe, and histaminergic in the tuberomammillary nucleus), whereas sleep-active neurons are GABAergic and located in the preoptic area of the hypothalamus:4 The discovery Inhibitors,research,lifescience,medical of the hypocretin (also called orexin) system has brought, new inroads into understanding Inhibitors,research,lifescience,medical the sleep-regulatory neural circuit.8 Hypocretin neurons are located in the lateral hypothalamus and have dense excitatory projections to all monoaminergic and cholinergic cell groups. Recent studies suggested that monoaminergic

and hypocretin neurons play a different and complementary role in wakefulness maintenance.4 For example, the dual effects of PI3K inhibitor hypocretins on arousal and food intake (orexin from “appetite-stimulating”) suggest, a more important role for hypocretins in Inhibitors,research,lifescience,medical the control of arousal maintenance related to energy homeostasis.8 In the same way, data summarized in the following section suggest, a role for the norepinephrine (NE)-containing neurons of the locus ceruleus (LC) in stress-induced arousal and concomitant anxiety.

Interactions between stress, anxiety, and sleep Anxiety and stress Anxiety is a universal emotion and it, would at. times be maladaptive not. to experience it; it is a necessary part of the response of the organism to a stress, ie, a threat, to the psychological or the physiological integrity Inhibitors,research,lifescience,medical of an individual. Inhibitors,research,lifescience,medical Anxiety may be polarized between a state and a trait. It may supervene at. some point, in the course of life, in which case anxiety is referred as a state. Anxiety trait. is a long-term feature of a person’s experience, present. throughout, life and considered to be a key feature of the avoidant or anxious personality disorder. It. probably reflects a lifetime maladaptive response to stress due to individual differences in biogenetic background, developmental influences, and early life experiences. There is no hard and fast, distinction between anxiety that may be considered as a normal, acceptable accompaniment of stress and the pathological state that warrants classification as a psychiatric click here disorder. In the latter, the nature of the stress is not. always clearly discernible. In other words, pathological anxiety could be characterized by a sense of fear, but. it. is differentiated from fear in that the threat is not immediate or always obvious. Whether normal or pathological, the constituent, features of anxiety always comprise indices of increased arousal or alertness that, could lead to sleep-wake alterations.

However, in the lipid infusion arm, glucose values were no differ

However, in the lipid infusion arm, glucose values were no different, but insulin levels did not fall over the course of the study visit. This is consistent with a greater requirement for insulin to maintain euglycemia following the standardized meal, consistent with peripheral insulin resistance. Formal assessment of peripheral insulin resistance,

using clamp techniques, was not performed in this study as demonstration of peripheral insulin resistance would not provide direct evidence for neuronal insulin resistance (Dresner et al. 1999; Shulman 2000). It is not Inhibitors,research,lifescience,medical possible to obtain hippocampal interstitial FFA levels or tissue biopsy samples from human healthy volunteers to confirm alterations in neuronal insulin Inhibitors,research,lifescience,medical signaling. Our experimental design, however, is based on proven models of peripheral insulin resistance (Dresner et al. 1999; Roden et al. 1999) taken together with recent evidence for transport of FFAs BIBR 1532 solubility dmso across the blood–brain barrier (Rapoport et al. 2001; Hamilton and Brunaldi 2007; Mitchell et al. 2011). The findings are consistent with published work by Karmi et al. (2010) demonstrating increased brain fatty acid uptake in humans with insulin resistance and

Inhibitors,research,lifescience,medical with McNay et al. (2010) work in animal models demonstrating increases in hippocampal glycolytic rates in response to insulin, and demonstration of impaired cognition in a model of insulin resistance induced by a high-fat diet (McNay et al. 2010). The cognitive test battery provided stimulation of the cognitive domains in which insulin resistance-associated Inhibitors,research,lifescience,medical deficits have been identified and is comparable in task difficulty with the test battery used by Baker et al. (2011). Impairment of the energy supply to sustain this activity would lead to depletion of the

intracellular energy stores. The primary purpose of the cognitive testing in this study was to stimulate neuronal activity, and hence the hypothesized stimulated Inhibitors,research,lifescience,medical neuronal glucose uptake via insulin signaling. The findings in this study of a reduction in PCr/ATP ratio with cognitive stimulation following lipid infusion to inhibit insulin signaling, and lack of change in the absence of lipid infusion to induce insulin resistance, Terminal deoxynucleotidyl transferase supports a role for insulin in maintaining neuronal glucose uptake and hence cellular energy production during increased neuronal activity. Observed performance on cognitive testing was not impaired following the lipid infusion, despite the reduction in PCr/ATP ratio. The 20-min cognitive test battery appears to have provided enough stimulation to result in a depletion of intracellular energy stores, and thus test the experimental hypothesis, but the sensitivity of the tests for subtle changes in performance after a brief intervention is limited.

Table 1 The distribution of Cosenza mutations in some provinces o

Table 1 The distribution of Cosenza mutations in some provinces of Iran We also studied the association of Mediterranean and Cosenza mutation with (1311C→T) haplotype. The haplotype analysis revealed that unlike Mediterranean G6PD, mutation was associated with (1311C) haplotype. Fifty eight samples, which have not Mediterranean and mutations, are kept for identification of other G6PD mutations. Conclusion The findings of the present study

indicate that G6PD Cosenza is a common mutation in Khuzestanian G6PD deficient individuals. Acknowledgment This study was financially supported by a grant (no. 3587) from the Shahid Chamran University of Ahvaz, Iran. Conflict of Interest: None Inhibitors,research,lifescience,medical declared
Duchenne muscular dystrophy (DMD) is a congenital, chronic degenerative muscle disorder that results in loss of ambulation, respiratory compromise and cardiac dysfunction (1). Corticosteroids are the standard of care for the treatment of DMD (1-4). Prednisone, prednisolone and deflazacort are the corticosteroids used to treat DMD. Inhibitors,research,lifescience,medical Corticosteroids have been shown to prolong independent ambulation, improve pulmonary

Inhibitors,research,lifescience,medical function, delay the onset of cardiomyopathy and reduce the incidence of selleck scoliosis (1, 2, 5). Here we examine the Canadian clinical experience with deflazacort. Deflazacort is an oxazoline derivative of prednisolone with anti-inflammatory and immunosuppressive activity (6, 7). The effect of deflazacort on the progression of symptoms in DMD as well as the side effect profile have been characterized (8-18). Compared to prednisone, deflazacort has been shown in other diseases to cause fewer side effects including better preservation of bone mass (19-22), less weight gain (19, 20, 22, 23), better lipid profile Inhibitors,research,lifescience,medical (20, 22, 24) and less glucose intolerance (24, 25). A direct comparison of deflazacort and prednisone in DMD has Inhibitors,research,lifescience,medical been studied in a multicenter, double-blind, randomized trial of 18 patients over one year of treatment (14). There was no significant difference in motor outcomes however, there

was less weight gain in the group treated with deflazacort compared to prednisone (2.17 kg vs. 5.08 kg) (14). Two patients developed small cataracts in the deflazacort group and none were observed in the prednisone group. Other side effects were equally distributed including Oxalosuccinic acid behaviour changes, increased appetite, cushingoid appearance, hirsutism and gastric symptoms (14). There is an international study planned to compare two prednisone dosing schedules to daily deflazacort (26). Biggar et al. (9) compared two different deflazacort protocols; one from Toronto (0.9 mg/kg daily) and one from Naples (0.6 mg/kg/d for the first 20 days of the month). Benefits were seen with both protocols, however, the higher daily dose, Toronto protocol, resulted in prolonged ambulation (77% at 15 years compared to 25% at 15 years) and patients were less likely to develop scoliosis (16% compared to 30%).