9 Results of recent clinical studies further raise concern over t

9 Results of recent clinical studies further raise concern over the modest advances that have been achieved over the last five decades in developing more effective drugs for treating schizophrenia. While meta-analyses comparing the first-generation antipsychotics to the secondgeneration antipsychotics

do suggest some modest Alisertib in vivo superiority of the second-generation Inhibitors,research,lifescience,medical antipsychotics, these effects are limited to positive symptoms known to be sensitive to D2 receptor antagonism.10 In the large-scale CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) trial, Lieberman et al11 compared several second-generation antipsychotics with a first-generation antipsychotic, perphenazine. The majority of patients in each group discontinued their antipsychotics owing to inefficacy or intolerable side effects. When clozapine was compared with other second-generation antipsychotics, Inhibitors,research,lifescience,medical it did exhibit modest but significant superiority over these other drugs. A separate study carried out in England, Cost Utility of the Latest Antipsychotic Drugs and Schizophrenia Study (CUtLASS 1), also found few differences in effectiveness between first-generation antipsychotics and second-generation antipsychotics in non-refractory patients.12 As pointed out by Lieberman,13 both the CATIE and the CUtLASS studies are “effectiveness” studies, which examine the

therapeutic response in real-world clinical situations. This design is Inhibitors,research,lifescience,medical markedly different from the randomized clinical trial of

Inhibitors,research,lifescience,medical “efficacy,” in which a new drug is compared with placebo in a very select group of patients subject to a myriad of exclusionary criteria. Thus, basing a drug discovery effort for schizophrenia on the assumption that it is primarily a disorder of dopaminergic dysfunction has led to the introduction of antipsychotics that are marginally more efficacious than their “progenitors,” chlorpromazine and haloperidol. Starting about 20 years ago, psychopharmacologists began to focus on other components of schizophrenia rather than just the antipsychotic responsive positive symptoms (ie, hallucinations, delusion, and thought disorder). Negative Inhibitors,research,lifescience,medical symptoms including apathy, poverty of thought, anhedonia, lack of drive, disorganization, and social isolation were observed to covary independently of positive symptoms, be much more enduring, and correlate inversely with outcome.14,15 With advances in neuropsychology, much more rigorous testing delineated the specific Thymidine kinase impairments in memory, problem-solving, and executive functions, which were noted a century ago with the designation of “dementia praecox.”16,17 At the same time, progress in both structural and functional brain imaging revealed substantial cortical involvement in schizophrenia. On average, cortical volume is reduced and lateral ventricular volume is increased in individuals with a first episode of schizophrenia, and these differences increase over the next 5 to 10 years.

It also showed dense islets of Langerhans (IL) which are prominen

It also showed dense islets of Langerhans (IL) which are prominently found amidst the pancreatic accini (PA). Some of the cells of the islets possessed light nuclei (LN), while most other had darkly stained nuclei (DN). Accini

presented normal MLN8237 clinical trial structure with all of them having cells filled with their secretion (Sc) (Fig. 2a, b). However the pancreas of STZ administered diabetic rats displayed damaged islets with severe necrosis (N). Mild to severe atrophy of the islets of Langerhans was found to be the most striking feature in these animals. The accini as well as islets were completely shrunken (Sk) and showed complete loss of structural integrity. In some of the sections, the dimensions of the islets was considerably reduced and shrunken (Fig. 2c, d). In Glibenclamide treated group, the islet (IL) appeared slightly shrunken as compared to normal control group but much revived as compared to diabetic control. The accini appeared

considerably destroyed and showed damaged cells (Dc) (Fig. 2e, f). ASCO treated group showed higher number of islets of Langerhans (IL) each having normal expanse and higher density of cells comparable with normal control group. Numbers of lightly stained cells were more in islets as compared to the other treated groups. Acini too appeared with sufficient amount of secretion in all of them (Fig. 2g, h). T. S. of kidney of the normal control rats revealed normal inhibitors glomerulus (G) surrounded by the Bowman’s Selleckchem AZD6738 capsule (Bc). Few RBC’s were found scattered in the glomerulus. Tubular regions (Tr) made up of PCT and DCT showed normal thickness of their epithelial lining, which appeared rather squamous in their form (Fig. 3a, b); whereas in diabetic control group glomerulus appeared shredded and shrunken (Sk). The Bowman’s capsule (Bc) showed increased diameter compared to normal. Convoluted tubules (Ct) appeared dilated and showed several breaks in its epithelium. Most of the tubules showed accumulation of amorphous material in their lumen which is probably

mucopolysaccharide (Fig. 3c, d). The T.S. of kidney of diabetic rats treated with Glibenclamide showed clear nephrons without before any accumulation in lumen of PCT and DCT, although haemolysis (ly) was evident occasionally. Tubules appeared hypertrophied (ht), while glomerulus showed onset of necrosis (Fig. 3e, f). T. S. of kidney of diabetic rats treated with the ASCO showed close resemblance to that of normal kidney. Glomerulus (G) appeared round and globular occupying nearly the entire inner space of Bowman’s capsule (Bc). Some of the convoluted tubules showed accumulation of amorphous, mucopolysaccharides (Mp); while most other tubules showed clear lumen which is an indication of partial recovery. Decrease in the tissue necrosis was also observed in group treated with ASCO (Fig. 3g, h). The liver is one of the organs that bear the brunt of chronic hyperglycaemia, since glucose is freely permeable to its cells.

Results Study selection Figure 1 presents the flow chart of ident

Results Study selection Figure 1 presents the flow chart of identified studies. The OVID search identified 3832 abstracts for screening. Due to the large number of abstracts identified and the need to answer three different research questions, the first stage of screening involved sorting the abstracts according to the three outcomes of interest: drivers of nonadherence, consequences of nonadherence, and studies on nonadherence and hospitalization rate. During this first screening, any abstracts that clearly did not match the inclusion criteria were also excluded. Thus in the second, Inhibitors,research,lifescience,medical outcome-specific, phase of screening, there were 149 potentially

relevant abstracts on drivers, 408 on consequences and

109 on hospitalization due to nonadherence. There were 37 full papers included in total: 15 studies on nonadherence drivers and 22 on consequences of nonadherence, of which 12 focused on the specific Inhibitors,research,lifescience,medical link between nonadherence and hospitalization. A quantitative meta-analysis was not performed for the link between nonadherence and hospitalization, due to lack of data on comparable outcome measure. Thus, a qualitative approach was taken for all outcomes. Inhibitors,research,lifescience,medical Figure 1. Study selection flow diagram. Details from the studies in this review, including study design, study population, definition of adherence and findings for key outcomes are presented in Tables 1​1–3. Table 1. Summary of findings on

potential positive and negative factors influencing adherence rates. Table 2. Summary of findings on consequence of non-adherence. Table 3. Results on a link between non-adherence and hospitalisation. Factors influencing adherence rates Fifteen papers [Acosta et al. 2009; Aldebot and de Mamani 2009; Inhibitors,research,lifescience,medical Ascher-Svanum, 2006; Borras et al. 2007; Hudson et al. 2004; Janssen et al. 2006; Linden et al. 2001; Loffler et al. 2003; McCann et al. 2009; Novick et al. 2010; LDN-193189 mw Olfson et al. 2006; Rettenbacher et al. 2004; Valenstein et al. 2004; Velligan et al. 2009; Weiden et al. 2004b] assessed drivers of nonadherence in schizophrenia; Inhibitors,research,lifescience,medical Edoxaban seven were prospective longitudinal studies [Acosta et al. 2009; Ascher-Svanum, 2006; Ascher-Svanum et al. 2006; Hudson et al. 2004; Janssen et al. 2006; Linden et al. 2001; Loffler et al. 2003; Novick et al. 2010] and six were cross-sectional studies such as interviews and surveys [Aldebot and de Mamani 2009; Borras et al. 2007; McCann et al. 2009; Olfson et al. 2006; Rettenbacher et al. 2004; Weiden et al. 2004b]. In addition, there was one retrospective database study [Valenstein et al. 2004] and one review/survey of experts [Velligan et al. 2009]. Ten of these studies [Ascher-Svanum 2006; Borras et al. 2007; Hudson et al. 2004; Janssen et al. 2006; Linden et al. 2001; Loffler et al. 2003; Novick et al. 2010; Olfson et al. 2006; Valenstein et al. 2004; Weiden et al.

Sertraline was administered from day 9 onwards to 12 volunteers,

Sertraline was administered from day 9 onwards to 12 volunteers, the other 12 receiving placebo sertraline. The CDR system was administered repeatedly on days 1, 2, and 25. Haloperidol produced impairments in attention on day 2 of the study, yet amazingly, with no intervening dosing, the second single dose administered 23 days later produced greater impairment. On measures affected the first time, the effects started sooner and were of greater magnitude, while functions not, affected on day 2 were impaired on day 25. Of 20 measures, 10 were impaired to a significantly greater extent on day Inhibitors,research,lifescience,medical 25 than day 2. This effect reflected a phenomenon seen in animals dosed

with haloperidol termed “time-dependent sensitization” and was the first, demonstration that such a phenomenon exists in man. In other drug-drug interaction work, no evidence was obtained for an interaction between the SSRI fluoxetine and the MLN8237 order 5-HT1A agonist Inhibitors,research,lifescience,medical flesinoxan.51 In the 11 studies described above, no interactions were seen. The same was true of the first of two interaction trials conducted with the novel antihypertensive Inhibitors,research,lifescience,medical moxonidine.52 In the first

trial, no interaction between moxonidine and the antidepressant moclobemide 300 mg was identified. However, in the second study, a clear interaction between moxonidine and lorazepam 1 mg was identified. In this trial, lorazepam 1 mg produced the profile of impairment characteristic Inhibitors,research,lifescience,medical of this type of benzodiazepine. Moxonidine 0.4 mg dosed alone produced no effects, but when the two drugs were codosed, the impairment identified was significantly greater than that of lorazepam 1 mg. This interaction was seen for the following CDR

measures: speed of detections in the digit vigilance task, simple reaction time, choice reaction time, and visual tracking. These were clear interactions, which would disrupt the attentional capacity of patients taking lorazepam 1 mg and moxonidine 0.4 mg together. Historical data, however,34 showed that the impairments with the combination were no greater than what would be produced Inhibitors,research,lifescience,medical by lorazepam 2 mg, which will give clinicians a frame of reference when advising patients of the likely consequence of taking the two medications together. Screening for desired cognitive Montelukast Sodium effects Here the purpose of cognitive testing is to identify desired cognitive effects, which are for the most part either reversals of existing deficits or improvements to normal functioning. Over the last, 20 years, there has been a massive investment, in research into agents to treat dementia, particularly AD. This has in turn led to interest in treating a range of conditions in which cognitive function is impaired, not least normal aging. The implicit, assumption of many researchers in this field is that impairments in function are potentially capable of being reversed, but that normal function cannot, be improved.53 This assumption is fallacious, as will be illustrated in the next section.

least 6 symptoms of inattention, and is closer to HKD Clinical

least 6 symptoms of inattention, and is closer to HKD. Clinical diagnoses such as ADHD or HKD are necessary for the fundamental decision of whether or not to treat. However, since these, like all psychiatric diagnoses, are based exclusively on symptoms, they can result from a wide range of causes and susceptibilities. Thus, diagnostic categories do not provide an optimal basis for neurobiological investigations, although they are a necessary Inhibitors,research,lifescience,medical starting point.5 In the case of ADHD, they have been the basis for an increasing number of structural as well as functional neuroimaging

studies. Functional imaging studies have used a wide variety of approaches, and none of the findings reported to date have been convincingly replicated. For this reason, and due to limitations of space, this brief review will focus on one simple question: what are the anatomic substrates associated with combined type ADHD? (In the text below, ADHD refers to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]1 combined type Inhibitors,research,lifescience,medical ADHD.) ADHD as a disorder cannot be considered without taking into account developmental factors, and an examination of the brain anatomy of ADHD must, be referenced to healthy brain development.

The most influential early work on brain development, was based on postmortem specimens from over 200 autopsy brains obtained from Inhibitors,research,lifescience,medical midprcgnancy through the first year of life, and a large collection of adult brains, but Inhibitors,research,lifescience,medical very few specimens (about 12) in the age range extending from childhood through adolescence. Yakovlev and Lecours demonstrated that myelination continued well beyond the first, year of life,6 but. they were circumspect about their more speculative findings, which they explicitly acknowledged were based on “a crude method of staining myelin sheath” of undetermined

reliability. Nevertheless, they tentatively concluded that. myelination proceeds along a caudal-rostral gradient. Because of the lack of postmortem tissue for children and adolescents, this finding has not been Inhibitors,research,lifescience,medical directly examined. In vivo magnetic resonance imaging The quantitative study of brain development in vivo NU7441 price during childhood and adolescence began in the late 1980s.7,8 Subsequent cross-sectional1,9-11 and mixed longitudinal/ Carnitine dehydrogenase cross-sectional studies12 have confirmed that although total brain volume changes negligibly between ages 5 and 18, this masks robust and complex changes in white and gray matter compartments. White matter volume and signal intensity increase linearly during this age range, presumably reflecting increasing myelination,11,13 and gray matter volume increases until early to mid-adolescence before decreasing during late adolescence,12 apparently representing synaptic pruning and reduction in neuropil, which has been documented during these developmental periods.

All the other derivatives showed moderate to weak activity Among

All the other derivatives showed moderate to weak activity. Among the series, replacement of the –OMe group on phenyl ring attached to pyrazoline moiety at C-5 carbon atom either by –CH3 (7e and 7l) or halogen like Cl substituent group (7g and 7n) resulted in a dramatic drop of inhibitory activity and in compound 7m, it was observed to be enhancing the lipoxygenase activity rather than inhibition. In conclusion, a new class of indole based scaffolds having pyrazole ring have been synthesized and evaluated for their in vitro

antioxidant activity and anti-inflammatory activity. Among the synthesized analogues, 7d have shown significant antioxidant potential and compound 7c yielded better anti-inflammatory activity and therefore become lead candidates for synthetic and biological evaluation. All authors Proteasome purification have none to declare. The authors are thankful to NMR Research center, Indian Institute of Science, Bangalore for providing spectral data. Also the authors are thankful to Mr. Rakshit, Microbiology department, Manasagangotri, Mysore for carrying out anti-inflammatory activity. “
“Breast Cancer Resistance Protein (BCRP) is a membrane-bound protein

and belongs to the ATP-binding cassette family. BCRP is also called as ABCG2 which is present in many normal tissues and solid tumors VRT752271 datasheet including blood–brain barrier, placenta, liver, small intestine, for adrenal gland, testis and stem cells.1 BCRP deliberate drug resistance to many anti-cancer agents such as irinotecan, topotecan, tyrosine kinase inhibitors and mitoxantrone. BCRP is ATP-binding cassette (ABC) efflux transporter

that deliberates multidrug resistance in breast cancer and also plays an important role in the absorption, distribution and elimination of drugs.1 and 2 It is of elementary significance to investigate the function and binding site of BCRP protein. BCRP contains 655-amino acid with a single nucleotide binding domain (NBD) and six transmembrane domains (TMD). BCRP is a half-transporter, and thus requires at least two NBDs to function as a drug efflux pump. Hence, functional BCRP exists as either homodimers or homo-multimers.3 and 4 3D structure of BCRP has not been solved in Protein Data Bank yet. Hence the aim of the current study is to construct the 3D structure of BCRP to investigate the interaction of ligands of BCRP in wild and mutated models in order to define possible binding sites. Protein sequence has been retrieved from UniProtKB/Swiss-Prot.5 Present study used Homology modeling methods to construct the 3D structure of Human BCRP. Human BCRP homology model was built using MODELLER (Fig. 2 and Fig. 3), a Computational algorithm for Protein structural assessment.

For example, CX614 and LY451646 are high-impact agents, and CX173

For example, CX614 and LY451646 are high-impact agents, and CX1739 and Org26575 are low-impact agents. In addition, there is evidence that AMPA receptor Galunisertib price potentiating agents have antidepressant actions in behavioral models as well as cellular targets of treatment response.87,88 Other than the in vitro studies of CX614 there is no direct evidence that AMPA receptor potentiating

drugs produce ketamine-like effects, such as activation of mTORC1 signaling and increased synaptogenesis. Further studies are required to determine if AMPA receptor potentiating agents influence these pathways and targets in vivo, and produce a rapid antidepressant response in models like CUS. While these Inhibitors,research,lifescience,medical novel targets, including AMPA receptor potentiating drugs and mGluR2/3 antagonists may prove to be rapid and effective antidepressant agents, it remains to be determined if they will also produce unwanted side effects. In addition, it is possible that the actions Inhibitors,research,lifescience,medical of these agents are closely

tied to synaptic levels of glutamate, since the efficacy of both depends on either blocking presynaptic glutamate actions Inhibitors,research,lifescience,medical at mGluR2/3 receptors, or potentiating postsynaptic actions of glutamate at AMPA receptors. Role of glycogen synthase kinase-3 (GSK-3) in the actions of ketamine: GSK-3 antagonists enhance the response to ketamine Another mechanism implicated in the actions of ketamine is regulation of GSK-3β. GSK-3β is a serine/threonine kinase that is inhibited by lithium and is thought to play a significant role in the therapeutic actions of lithium in bipolar patients. Levels of GSK-3β are also increased in bipolar depressed patients.89 Inhibitors,research,lifescience,medical The function of GSK3 is inhibited by phosphorylation of specific amino acid residues. Interestingly, a recent study has demonstrated that ketamine Inhibitors,research,lifescience,medical increases the phosphorylation of these inhibitory

sites and that mice with a knockin of GSK-β that is resistant to phosphorylation do not show an antidepressant response to ketamine.90 These studies demonstrate that inhibition of GSK-3β significantly contributes to the actions of ketamine. This may occur in part by blocking the LTD-promoting actions of GSK-3β, which would enhance ketamine induction of the LTP-like synaptogenic effects (Figure 3). The interaction between ketamine and GSK-β inhibitors Adenosine is further demonstrated in a recent report. This study found that coadministration of ketamine and a selective GSK-3β inhibitor, SB216763, at low doses that have no effect when used alone, produce a significant antidepressant behavioral effect, as well as induction of mTORC1 signaling and synaptogenesis in the medial PFC.91 Similar effects were found with lithium, raising the possibility that ketamine plus lithium combination therapy could have reduced side effects compared with the higher dose of ketamine that is currently used.

The challenge is that several studies have shown more than 30% of

The challenge is that several studies have shown more than 30% of women with pelvic floor dysfunction are not able to contract the pelvic floor muscles correctly even after thorough individual teaching and feedback (Benvenuti et al 1987, Bump et al 1991, Bø et al 1988). The most common errors

are to bear down or to use hip adductor, gluteal, or abdominal muscles instead of the pelvic floor find more muscles (Bump et al 1991, Bø et al 1988). Group Libraries training of pelvic floor muscles has been shown in several randomised controlled trials to be effective, but these programs included individual instruction and feedback of the contraction (Bø et al 1990, Bø et al 1999, Mørkved and Bø 1997, Mørkved et al 2003). It is not yet known whether it is possible to teach Selleckchem Alpelisib women participating in a general group-based exercise class to contract the pelvic floor muscles. Culligan et al (2010) concluded, on the basis of their finding that Pilates training produced similar strength gains to pelvic floor muscle

training, that their results may ‘lead to widespread use of Pilates-based exercise programs to treat and prevent pelvic floor dysfunction’. In our opinion that conclusion is premature because no randomised trials have demonstrated benefical effects of Pilates exercise on clinically important outcomes (continence) in a sample of incontinent women. Indeed, observational data suggest that this is not the case: a study on group fitness instructors showed that the prevalence of incontinence was the same amongst female yoga and Pilates instructors as in the general population, suggesting that the exercises did not provide a beneficial effect (Bø et al 2011). The suggestion of an association or causal link between breathing, posture, and pelvic floor muscle dysfunction should

be tested in case-control or cohort studies with blinded assessors. A large cross-sectional study found associations between incontinence, enough low back pain, and respiratory disease (Smith et al 2006), but it is quite possible the associations were confounded, so that while participants had multiple complaints at the same time the conditions were not causally related. Cross-sectional studies usually provide weak evidence of causality. There are two contradictory hypotheses on the effect of general exercise on the pelvic floor, previously described by Bø (2004). One hypothesis holds that general exercise makes pelvic floor muscles co-contract, and thus strengthens pelvic floor muscles and prevents stress urinary incontinence. The other hypothesis is that repetitive or heavy impact on the pelvic floor, such as is caused by heavy lifting or marathon running, may fatigue, stretch, and weaken the muscles.

Only a few studies in postmortem brain tissue on a

Only a few studies in postmortem brain tissue on a relatively small number of subjects have attempted to estimate the number of neurons in such subcortical structures as hypothalamus,

dorsal raphe nucleus, locus ceruleus, and amygdala.44-52 Results of these subcortical histopathological studies are somewhat inconsistent. Increases, decreases, or no change in the cell number or density are reported in the hypothalamus and brain stem nuclei in depressed subjects. Stereological investigation of specific types of hypothalamic neurons reveals an increase in the numbers of arginine-vasopressin (AVP)-immunoreactive neurons, oxytocin-expressing neurons, Inhibitors,research,lifescience,medical and corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus in subjects with BPD or MDD, compared to normal controls.44,45 Moreover, Inhibitors,research,lifescience,medical Selleck Pictilisib increases in CRH mRNA, and in the number of CRH neurons colocalizing AVP are also found in depressed patients.46,47 These findings

of increases in specific immunoreactive neurons arc consistent with the evidence of activation of the hypothalamicpituitary-adrenal (HPA) Inhibitors,research,lifescience,medical axis in some subsets of depressed patients.48 On the other hand, decreased number and density of nitric oxide synthase-containing neurons in the paraventricular hypothalamic nucleus are described in a small group of subjects with either MDD or BPD.49 Subtle structural abnormalities have been reported in mood disorders in the monoaminergic brain stem nuclei, the major sources of serotonin (dorsal raphe nucleus) and norepinephrine (locus Inhibitors,research,lifescience,medical ceruleus) projections to the cerebral cortex. An increased number and density

of tryptophan hydroxylase immunoreactive neurons is observed in the dorsal raphe nucleus of suicide victims with MDD compared with controls.50 In suicide victims, Arango et al51 report fewer pigmented neurons within the rostral locus ceruleus. Another study in a larger number of subjects found no differences in the number Inhibitors,research,lifescience,medical of Linifanib (ABT-869) pigmented neurons in the locus ceruleus between subjects with MDD (most were suicides) and control subjects.52 Although the number of neurons in the locus ceruleus does not appear altered in MDD, CRH immunoreactivity is increased in the locus ceruleus and pontine dorsal and median raphe nuclei.53,54 No changes in neuronal densities were detected in amygdala in subjects with either M’DD or BPD, as compared to normal controls.17 These postmortem findings suggest that some changes in the morphology of hypothalamic neurons and brain stem neurons may take place in mood disorders. However, future studies employing stereological techniques and a larger number of subjects are required to determine the exact pathology in these regions in depression.

However, some attempts at clarification have been proposed, parti

However, some attempts at clarification have been proposed, particularly in thoroughly reflecting? on the subject: “Three major dichotomies appear in the structure of the current talk on eugenism: the dichotomy between the individual and the social, the distinction of the intentions and the effects, finally the alternative between coercion and voluntary decision” Inhibitors,research,lifescience,medical (47). Concerning muscular dystrophy, according to these criteria, confusion is inevitable, both in the social incidence, in doubtful intentions, and in a conditioning of consent, despite numerous protections which have already been proposed (genetic counseling, ethical committees,

subsequent legislations …). If an urgent Inhibitors,research,lifescience,medical Legislation has to intervene, it will not be that claimed

now concerning euthanasia, but that allowing the numerous contradictions harming or damaging the priority fight against illness to be clarified. Conclusion The Universal Declaration of human rights, proclaimed by the United Nations General Assembly on 10th December 1948, established in the third article: “Everyone has the right to life, liberty and security of person” (8). During more than one century, intellectual attempts standardized the value of Man according to the shape Inhibitors,research,lifescience,medical of his skull, the prominence of his mouth, the colour of his skin etc. In a similar way, the qualities of Man have been quantified according to the measures of his intelligence, of his physical performances, while mentally and handicapped people have been excluded separately. Genetics later demonstrated that any form of racism is absurd. Ideally, it must be also the closest joint liability of Medicine and Law to protect Humans from any

discrimination Inhibitors,research,lifescience,medical just based upon the severity of a specific disease. Acknowledgments The Authors are deeply graceful for help and comprehension received for translation and publication of this work. In Memoriam Un garçon avait compris que Inhibitors,research,lifescience,medical la force de sa vie pouvait, devait, compenser la faiblesse de ses muscles. Son exemple était une richesse majeure (45). Il nous manque beaucoup, et ce travail a été réalisé en pensant à lui. Institut Duchenne International
Lysosomal storage diseases (LSDs) are a large group of disorders caused by a deficiency of specific enzymes MTMR9 responsible for the degradation of substances present in lysosomes. In the past few years, selleck treatments for LSDs were non specific and could only cope with signs and symptoms of the diseases. A successful therapeutic approach to LSDs should instead address to the underlying causes of the diseases, thus helping the degradation of the accumulated metabolites in the various organs, and at the same time preventing their further deposition. One way is to see to an available source of the deficient enzyme: bone marrow transplantation, enzyme replacement therapy and gene therapy are based on this rationale.