miR-106b is a novel target to promote muscle regeneration and restore satellite stem cell function in injured Duchenne dystrophic muscle.

Satellite cells (SCs), muscle stem cells, display functional heterogeneity, and dramatic changes linked to their regenerative capabilities are associated with muscle-wasting diseases. SC behavior is related to endogenous expression of the myogenic transcription factor MYF5 and the propensity to enter into the cell cycle. Here, we report a role for miR-106b reinforcing MYF5 inhibition and blocking cell proliferation in a subset of highly quiescent SC population. miR-106b down-regulation occurs during SC activation and is required for proper muscle repair. In addition, miR-106b is increased in dystrophic mice, and intramuscular injection of antimiR in injured mdx mice enhances muscle regeneration promoting transcriptional changes involved in skeletal muscle differentiation. miR-106b inhibition promotes the engraftment of human muscle stem cells. Furthermore, miR-106b is also high in human dystrophic muscle stem cells and its inhibition improves intrinsic proliferative defects and increases their myogenic potential. This study demonstrates that miR-106b is an important modulator of SC quiescence, and that miR-106b may be a new target to develop therapeutic strategies to promote muscle regeneration improving the regenerative capabilities of injured dystrophic muscle.

Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy.

BACKGROUND AND OBJECTIVES: To study the clinical and laboratory features of antineurofascin-155 (NF155)-positive autoimmune nodopathy (AN). METHODS: Patients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up. RESULTS: Forty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2-4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = -0.88, p < 0.001) and with maximum I-RODS achieved (r = -0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients. DISCUSSION: Anti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab.

Antibodies to the Caspr1/contactin-1 complex in chronic inflammatory demyelinating polyradiculoneuropathy.

Previous studies have described the clinical, serological and pathological features of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and antibodies directed against the paranodal proteins neurofascin-155, contactin-1 (CNTN1), contactin-associated protein-1 (Caspr1), or nodal forms of neurofascin. Such antibodies are useful for diagnosis and potentially treatment selection. However, antibodies targeting Caspr1 only or the Caspr1/CNTN1 complex have been reported in few patients with CIDP. Moreover, it is unclear if these patients belong to the same pathophysiological subgroup. Using cell-based assays in routine clinical testing, we identified sera from patients with CIDP showing strong membrane reactivity when both CNTN1 and Caspr1 were co-transfected (but not when CNTN1 was transfected alone). Fifteen patients (10 male; aged between 40 and 75) with antibodies targeting Caspr1/CNTN1 co-transfected cells were enrolled for characterization. The prevalence of anti-Caspr1/CNTN1 antibodies was 1.9% (1/52) in the Sant Pau CIDP cohort, and 4.3% (1/23) in a German cohort of acute-onset CIDP. All patients fulfilled European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite diagnostic criteria for CIDP. Seven (47%) were initially diagnosed with Guillain-Barré syndrome due to an acute-subacute onset. Six (40%) patients had cranial nerve involvement, eight (53%) reported neuropathic pain and 12 (80%) ataxia. Axonal involvement and acute denervation were frequent in electrophysiological studies. Complete response to intravenous immunoglobulin was not observed, while most (90%) responded well to rituximab. Enzyme-linked immunosorbent assay (ELISA) and teased nerve fibre immunohistochemistry confirmed reactivity against the paranodal Caspr1/CNTN1 complex. Weaker reactivity against Caspr1 transfected alone was also detected in 10/15 (67%). Sera from 13 of these patients were available for testing by ELISA. All 13 samples reacted against Caspr1 by ELISA and this reactivity was enhanced when CNTN1 was added to the Caspr1 ELISA. IgG subclasses were also investigated by ELISA. IgG4 was the predominant subclass in 10 patients, while IgG3 was predominant in other three patients. In conclusion, patients with antibodies to the Caspr1/CNTN1 complex display similar serological and clinical features and constitute a single subgroup within the CIDP syndrome. These antibodies likely target Caspr1 primarily and are detected with Caspr1-only ELISA, but reactivity is optimal when CNTN1 is added to Caspr1 in cell-based assays and ELISA.

Dopamine D4 Receptor Is a Regulator of Morphine-Induced Plasticity in the Rat Dorsal Striatum.

Long-term exposition to morphine elicits structural and synaptic plasticity in reward-related regions of the brain, playing a critical role in addiction. However, morphine-induced neuroadaptations in the dorsal striatum have been poorly studied despite its key function in drug-related habit learning. Here, we show that prolonged treatment with morphine triggered the retraction of the dendritic arbor and the loss of dendritic spines in the dorsal striatal projection neurons (MSNs). In an attempt to extend previous findings, we also explored whether the dopamine D4 receptor (D4R) could modulate striatal morphine-induced plasticity. The combined treatment of morphine with the D4R agonist PD168,077 produced an expansion of the MSNs dendritic arbors and restored dendritic spine density. At the electrophysiological level, PD168,077 in combination with morphine altered the electrical properties of the MSNs and decreased their excitability. Finally, results from the sustantia nigra showed that PD168,077 counteracted morphine-induced upregulation of µ opioid receptors (MOR) in striatonigral projections and downregulation of G protein-gated inward rectifier K+ channels (GIRK1 and GIRK2) in dopaminergic cells. The present results highlight the key function of D4R modulating morphine-induced plasticity in the dorsal striatum. Thus, D4R could represent a valuable pharmacological target for the safety use of morphine in pain management.

Growth characterization in a cohort of renal allograft recipients.

INTRODUCTION: Growth retardation is a common problem in children with CKD. This study aims to describe growth, prevalence of short stature before RTx, catch-up growth after RTx, and associated factors. METHODS: We retrospectively reviewed 74 renal allograft recipients who underwent RTx at Fundación Cardioinfantil, Colombia, between January 2008 and September 2016 with follow-up for 2 years afterwards. Pre-RTx Height_SDS and demographic characteristics were compared between children with normal and short stature. Post-RTx Height_SDS at 1 and 2 years post-RTx and FAH, when available, were retrieved. Children were classified into catch-up growth and no catch-up growth groups depending on whether or not Height_SDS increased ≥0.5 per year within the first 2 years post-RTx. Possible associated factors were compared. RESULTS: Seventy-four patients were included. Mean age at RTx was 11 ± 4.0 years, and 43.2% (32/74) were females. Mean Height_SDS for the entire study population at pre-RTx was -2.8 ± 1.5. Before RTx, 68.9% (51/74) had short stature, and 44.6% (33/74) had severe short stature. 37.2% presented catch-up growth post-RTx. Time on dialysis was associated with short pre-RTx stature (OR 1.66; 95% CI [1.15-2.39]; P = .006) and catch-up growth (OR 2.15; 95% CI [1.15-3.99]; P = .016). 44.59% (33/74) reached FAH, and 48.4% (16/33) presented short FAH. CONCLUSIONS: Growth continues to be suboptimal after RTx. Given that pre-RTx height is a significantly associated factor, it is important to plan early interventions in terms of growth improvement in these children.

Pharmacological activation of dopamine D4 receptor modulates morphine-induced changes in the expression of GAD65/67 and GABAB receptors in the basal ganglia.

Dopamine D4 receptor (D4R) stimulation, in a putative D4R/µ opioid heteroreceptor (MOR) complex, counteracts the molecular, cellular and behavioural actions of morphine which are associated with morphine addiction, without any effect on its analgesic properties. In the present work, we have evaluated the role of D4R in modulating the effects of a continuous treatment with morphine on the GABAergic system in the basal ganglia. It has been demonstrated that the co-administration of a D4R agonist together with morphine leads to a restoration of GABA signaling by preventing drug-induced changes in GAD65/67 expression in the caudate putamen, globus palidus and substantia nigra. Results from GABABR1 and GABABR2 expression suggest a role of D4R in modulation of the GABAB heteroreceptor complexes along the basal ganglia, especially in the functional divisions of the caudate putamen. These results provide a new proof of the functional interaction between D4R and MOR and we postulate this putative heteroreceptor complex as a key target for the development of a new strategy to prevent the addictive effects of morphine in the treatment of pain. This article is part of the Special Issue entitled 'Receptor heteromers and their allosteric receptor-receptor interactions'.

Selective ablation of striatal striosomes produces the deregulation of dopamine nigrostriatal pathway.

The striatum is a complex structure in which the organization in two compartments (striosomes and matrix) have been defined by their neurochemical profile and their input-output connections. The striosomes receive afferences from the limbic brain areas and send projections to the dopamine neurons of the substantia nigra pars compacta. Thereby, it has been suggested that the striosomes exert a limbic control over the motor function mediated by the surrounding matrix. However, the functionality of the striosomes are not completely understood. To elucidate the role of the striosomes on the regulation of the nigral dopamine neurons, we have induced specific ablation of this compartment by striatal injections of the neurotoxin dermorphin-saporin (DS) and dopamine neurotransmission markers have been analyzed by immunohistochemistry. The degeneration of the striosomes resulted in a nigrostriatal projections imbalance between the two striatal compartments, with an increase of the dopamine neurotransmission in the striosomes and a decrease in the matrix. The present results highlight the key function of the striosomes for the maintenance of the striatal dopamine tone and would contribute to the understanding of their involvement in some neurological disorders such as Huntington's disease.

A Roma founder BIN1 mutation causes a novel phenotype of centronuclear myopathy with rigid spine.

OBJECTIVE: To describe a large series of BIN1 patients, in which a novel founder mutation in the Roma population of southern Spain has been identified. METHODS: Patients diagnosed with centronuclear myopathy (CNM) at 5 major reference centers for neuromuscular disease in Spain (n = 53) were screened for BIN1 mutations. Clinical, histologic, radiologic, and genetic features were analyzed. RESULTS: Eighteen patients from 13 families carried the p.Arg234Cys variant; 16 of them were homozygous for it and 2 had compound heterozygous p.Arg234Cys/p.Arg145Cys mutations. Both BIN1 variants have only been identified in Roma, causing 100% of CNM in this ethnic group in our cohort. The haplotype analysis confirmed all families are related. In addition to clinical features typical of CNM, such as proximal limb weakness and ophthalmoplegia, most patients in our cohort presented with prominent axial weakness, often associated with rigid spine. Severe fat replacement of paravertebral muscles was demonstrated by muscle imaging. This phenotype seems to be specific to the p.Arg234Cys mutation, not reported in other BIN1 mutations. Extreme clinical variability was observed in the 2 compound heterozygous patients for the p.Arg234Cys/p.Arg145Cys mutations, from a congenital onset with catastrophic outcome to a late-onset disease. Screening of European Roma controls (n = 758) for the p.Arg234Cys variant identified a carrier frequency of 3.5% among the Spanish Roma. CONCLUSION: We have identified a BIN1 founder Roma mutation associated with a highly specific phenotype, which is, from the present cohort, the main cause of CNM in Spain.

Transcriptomic integration of D4R and MOR signaling in the rat caudate putamen.

Morphine binding to opioid receptors, mainly to µ opioid receptor (MOR), induces alterations in intracellular pathways essential to the initial development of addiction. The activation of the dopamine D4 receptor (D4R), which is expressed in the caudate putamen (CPu), mainly counteracts morphine-induced alterations in several molecular networks. These involve transcription factors, adaptive changes of MOR signaling, activation of the nigrostriatal dopamine pathway and behavioural effects, underlining functional D4R/MOR interactions. To shed light on the molecular mechanisms implicated, we evaluated the transcriptome alterations following acute administration of morphine and/or PD168,077 (D4R agonist) using whole-genome microarrays and a linear regression-based differential expression analysis. The results highlight the development of a unique transcriptional signature following the co-administration of both drugs that reflects a countereffect of PD168,077 on morphine effects. A KEGG pathway enrichment analysis using GSEA identified 3 pathways enriched positively in morphine vs control and negatively in morphine + PD168,077 vs morphine (Ribosome, Complement and Coagulation Cascades, Systemic Lupus Erythematosus) and 3 pathways with the opposite enrichment pattern (Alzheimer's Disease, Neuroactive Ligand Receptor Interaction, Oxidative Phosphorilation). This work supports the massive D4R/MOR functional integration at the CPu and provides a gateway to further studies on the use of D4R drugs to modulate morphine-induced effects.

PITX2 Enhances the Regenerative Potential of Dystrophic Skeletal Muscle Stem Cells.

Duchenne muscular dystrophy (DMD), one of the most lethal genetic disorders, involves progressive muscle degeneration resulting from the absence of DYSTROPHIN. Lack of DYSTROPHIN expression in DMD has critical consequences in muscle satellite stem cells including a reduced capacity to generate myogenic precursors. Here, we demonstrate that the c-isoform of PITX2 transcription factor modifies the myogenic potential of dystrophic-deficient satellite cells. We further show that PITX2c enhances the regenerative capability of mouse DYSTROPHIN-deficient satellite cells by increasing cell proliferation and the number of myogenic committed cells, but importantly also increasing dystrophin-positive (revertant) myofibers by regulating miR-31. These PITX2-mediated effects finally lead to improved muscle function in dystrophic (DMD/mdx) mice. Our studies reveal a critical role for PITX2 in skeletal muscle repair and may help to develop therapeutic strategies for muscular disorders.

Anti-NF155 chronic inflammatory demyelinating polyradiculoneuropathy strongly associates to HLA-DRB15.

BACKGROUND: The aim of the research is to study the human leukocyte antigen (HLA) class II allele frequencies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with anti-neurofascin 155 (NF155) antibodies. METHODS: Thirteen anti-NF155+ and 35 anti-NF155 negative (anti-NF155neg) CIDP patients were included in a case-control study. The frequencies of the DRB1 HLA allele were analyzed in all patients while DQ frequencies were only studied in patients sharing the DRB1*15 allele. In silico HLA-peptide binding and NF155 antigenicity, predictions were performed to analyze overlap between presented peptides and antigenic regions. RESULTS: DRB1*15 alleles (DRB1*15:01 and DRB1*15:02) were present in 10 out of 13 anti-NF155+ CIDP patients and in only 5 out of 35 anti-NF155neg CIDP patients (77 vs 14%; OR = 20, CI = 4.035 to 99.13). DRB1*15 alleles appeared also in significantly higher proportions in anti-NF155+ CIDP than in normal population (77 vs 17%; OR = 16.9, CI = 4.434 to 57.30). Seven anti-NF155+ CIDP patients (53%) and 5 anti-NF155neg CIDP patients had the DRB1*15:01 allele (OR = 7, p = 0.009), while 3 anti-NF155+ CIDP patients and none of the anti-NF155neg CIDP patients had the DRB1*15:02 allele (OR = 23.6, p = 0.016). In silico analysis of the NF155 peptides binding to DRB1*15 alleles showed significant overlap in the peptides presented by the 15:01 and 15:02 alleles, suggesting functional homology. CONCLUSIONS: DRB1*15 alleles are the first strong risk factor associated to a CIDP subset, providing additional evidence that anti-NF155+ CIDP patients constitute a differentiated disease within the CIDP syndrome.

Dopamine D4 receptor stimulation prevents nigrostriatal dopamine pathway activation by morphine: relevance for drug addiction.

Morphine is one of the most effective drugs used for pain management, but it is also highly addictive. Morphine elicits acute and long-term adaptive changes at cellular and molecular level in the brain, which play a critical role in the development of tolerance, dependence and addiction. Previous studies indicated that the dopamine D4 receptor (D4 R) activation counteracts morphine-induced adaptive changes of the µ opioid receptor (MOR) signaling in the striosomes of the caudate putamen (CPu), as well as the induction of several Fos family transcription factors. Thus, it has been suggested that D4 R could play an important role avoiding some of the addictive effects of morphine. Here, using different drugs administration paradigms, it is determined that the D4 R agonist PD168,077 prevents morphine-induced activation of the nigrostriatal dopamine pathway and morphological changes of substantia nigra pars compacta (SNc) dopamine neurons, leading to a restoration of dopamine levels and metabolism in the CPu. Results from receptor autoradiography indicate that D4 R activation modulates MOR function in the substantia nigra pars reticulata (SNr) and the striosomes of the CPu, suggesting that these regions are critically involved in the modulation of SNc dopamine neuronal function through a functional D4 R/MOR interaction. In addition, D4 R activation counteracts the rewarding effects of morphine, as well as the development of hyperlocomotion and physical dependence without any effect on its analgesic properties. These results provide a novel role of D4 R agonist as a pharmacological strategy to prevent the adverse effects of morphine in the treatment of pain.

Rituximab in treatment-resistant CIDP with antibodies against paranodal proteins.

OBJECTIVE: To describe the response to rituximab in patients with treatment-resistant chronic inflammatory demyelinating polyneuropathy (CIDP) with antibodies against paranodal proteins and correlate the response with autoantibody titers. METHODS: Patients with CIDP and IgG4 anti-contactin-1 (CNTN1) or anti-neurofascin-155 (NF155) antibodies who were resistant to IV immunoglobulin and corticosteroids were treated with rituximab and followed prospectively. Immunocytochemistry was used to detect anti-CNTN1 and anti-NF155 antibodies and ELISA with human recombinant CNTN1 and NF155 proteins was used to determine antibody titers. RESULTS: Two patients had a marked improvement; another patient improved slightly after 10 years of stable, severe disease; and the fourth patient had an ischemic stroke unrelated to treatment and was lost to follow-up. Autoantibodies decreased in all patients after rituximab treatment. CONCLUSIONS: Rituximab treatment is an option for patients with CIDP with IgG4 anti-CNTN1/NF155 antibodies who are resistant to conventional therapies. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that rituximab is effective for patients with treatment-resistant CIDP with IgG4 anti-CNTN1 or anti-NF155 antibodies.

Cambio en la clasificación macroscópica de la apendicitis. ¿Tiene algún impacto? Estudio retrospectivo en un Hospital Universitario Pediátrico / Change in the macroscopic classification of appendicitis. Does it have any impact? Retrospective study in a Pediatric teaching hospital

Antecedentes. La definición actual de apendicitis diferencia la aguda en apéndices no perforados y perforados. Esta clasificación describe los apéndices perforados como aquellos con la presencia de un orificio visible en el apéndice o la presencia de un fecalito libre en la cavidad y ha cambiado el manejo postoperatorio actual. Objetivo. Determinar si el cambio en la definición macroscópica de la apendicitis aguda tiene alguna influencia en la duración de la estancia hospitalaria y la tasa de complicaciones dado el cambio en el manejo antibiótico postoperatorio. Materiales y métodos. Se llevó a cabo un rastreo de aquellos pacientes llevados a cirugía con diagnóstico de apendicitis aguda durante el primer semestre del año 2009 y el segundo semestre del año 2011 en la Fundación HOMI. Se excluyeron los pacientes llevados a laparoscopia diagnóstica por estudio del dolor abdominal, apendicectomias incidentales y los pacientes manejados en el protocolo de apendicectomía de Intervalo. Resultados. Se observó una disminución en el número de días de hospitalización/año y en el número de dosis de antibiótico/año y reducción en el número de complicaciones, lo cual demuestra que la clasificación y el protocolo de manejo actual no se correlacionan con un aumento en el número de complicaciones y se asocia con menores costos. Conclusión. El cambio en la clasificación macroscópica y el aportar la nueva definición sobre apendicitis perforada ha logrado disminuir la estancia hospitalaria y la cantidad de antibióticos utilizados sin una repercusión significativa en la tasa de complicaciones.

Background. The current definition differences the acute appendix in nonperforated and perforated. This classification describes the perforated appendicitis as those with the presence of a visible hole in the appendix or the presence of a free fecalito in the cavity and changed the postoperative current management. Objective. Determine whether the change in the macroscopic definition of acute appendicitis have any influence on the length of hospital stay and complication rates given the change in the post-operative antibiotic treatment. Materials and Methods. Patients undergoing surgery with a diagnosis of acute appendicitis in the first half of 2009 and the second half of 2011. Patients excluded were those taken to surgery for diagnostic laparoscopy by study of abdominal pain, also incidental appendectomy and patients managed in the protocol of appendectomy interval. Results. A decrease in the number of hospital days /year and the number of doses of antibiotic/ year and decrease in the number of complications was observed which demonstrates that the classification and current management protocol are not correlated with an increase in number of complications and is associated with lower costs. Conclusions. The change in the macroscopic classification and provide the new definition of perforated appendicitis has reduced hospital stay and the amount of antibiotics used without a significant impact on the rate of complications.

Dopamine D4 receptor counteracts morphine-induced changes in µ opioid receptor signaling in the striosomes of the rat caudate putamen.

The mu opioid receptor (MOR) is critical in mediating morphine analgesia. However, prolonged exposure to morphine induces adaptive changes in this receptor leading to the development of tolerance and addiction. In the present work we have studied whether the continuous administration of morphine induces changes in MOR protein levels, its pharmacological profile, and MOR-mediated G-protein activation in the striosomal compartment of the rat CPu, by using immunohistochemistry and receptor and DAMGO-stimulated [35S]GTPγS autoradiography. MOR immunoreactivity, agonist binding density and its coupling to G proteins are up-regulated in the striosomes by continuous morphine treatment in the absence of changes in enkephalin and dynorphin mRNA levels. In addition, co-treatment of morphine with the dopamine D4 receptor (D4R) agonist PD168,077 fully counteracts these adaptive changes in MOR, in spite of the fact that continuous PD168,077 treatment increases the [3H]DAMGO Bmax values to the same degree as seen after continuous morphine treatment. Thus, in spite of the fact that both receptors can be coupled to Gi/0 protein, the present results give support for the existence of antagonistic functional D4R-MOR receptor-receptor interactions in the adaptive changes occurring in MOR of striosomes on continuous administration of morphine.

Early modulation by the dopamine D4 receptor of morphine-induced changes in the opioid peptide systems in the rat caudate putamen.

The peptides dynorphin and enkephalin modulate many physiological processes, such as motor activity and the control of mood and motivation. Their expression in the caudate putamen (CPu) is regulated by dopamine and opioid receptors. The current work was designed to explore the early effects of the acute activation of D4 and/or µ opioid receptors by the agonists PD168,077 and morphine, respectively, on the regulation of the expression of these opioid peptides in the rat CPu, on transcription factors linked to them, and on the expression of µ opioid receptors. In situ hybridization experiments showed that acute treatment with morphine (10 mg/kg) decreased both enkephalin and dynorphin mRNA levels in the CPu after 30 min, but PD168,077 (1 mg/kg) did not modify their expression. Coadministration of the two agonists demonstrated that PD168,077 counteracted the morphine-induced changes and even increased enkephalin mRNA levels. The immunohistochemistry studies showed that morphine administration also increased striatal µ opioid receptor immunoreactivity but reduced P-CREB expression, effects that were blocked by the PD168,077-induced activation of D4 receptors. The current results present evidence of functional D4 -µ opioid receptor interactions, with consequences for the opioid peptide mRNA levels in the rat CPu, contributing to the integration of DA and opioid peptide signaling.

Bulbar involvement in patients with antiganglioside antibodies against NeuNAc(alpha2-3)Gal.

BACKGROUND: Reactivity against terminal NeuNAc(alpha2-3)Gal, common to several gangliosides such as GD1a, GT1b and GM3, has rarely been reported. The authors recently described a patient with a clinical picture of acute relapsing sensory ataxic neuropathy and bulbar involvement in whom they demonstrated concomitant reactivity against NeuNAc(alpha2-3)Gal and disialosyl epitopes. The authors suggested a correlation between NeuNAc(alpha2-3)Gal reactivity and bulbar involvement. AIM: To determine the frequency of reactivity against terminal NeuNAc(alpha2-3)Gal in acute and chronic immune-mediated disorders, and its possible correlation with bulbar involvement. METHODS: The authors retrospectively reviewed reactivity in the serum of more than 3000 consecutive patients with acute and chronic disorders in which antiganglioside antibodies were studied. The authors selected those patients who were simultaneously positive, by ELISA or thin-layer chromatography, for IgG or IgM antibodies anti-GM3, GD1a and GT1b, and reviewed their clinical features. RESULTS: Reactivity against NeuNAc(alpha2-3)Gal, shared by GM3, GD1a and GT1b gangliosides, was detected in 10 patients: isolated in one patient, and concomitant with reactivity against other gangliosides in the remaining patients. Reactivity against NeuNAc(alpha2-3)Gal was frequently associated (8/10) with symptoms suggestive of bulbar involvement, such as dysphagia, dysarthria or dysphonia. Severe respiratory failure requiring mechanical ventilation was observed in four patients. CONCLUSIONS: Reactivity against the NeuNAc(alpha2-3)Gal epitope is rare and is generally found in association with reactivity against the disialosyl epitope. It can be detected in patients with acute or chronic disorders and could be a serological marker of clinical bulbar involvement and, to a lesser extent, associated with the development of severe respiratory failure.

Bots (Diptera: Oestridae) infesting a neotropical forest rodent, Proechimys semispinosus (Rodentia: Echimyidae), in Panama.

Botfly larvae (Cuterebra sp.) infesting spiny rats (Proechimys semispinosus) in 8 small islands in the Panama Canal were studied. Rats were live trapped monthly on each island from January 1991 through February 2000 and visually examined for the presence of bots. Overall, bot prevalence was 4.6% and differed statistically among island rat populations. Rats were simultaneously infested by as many as 4 bots. Overall bot intensity was 1.3 bots per infested rat and did not differ among islands. Mean bot density across all islands was 0.0111 and was greater during the dry seasons than during the rainy seasons, but it did not differ among islands. Bots were found during all the 12 calendar months, suggesting a multivoltine reproductive schedule. Although bot activity varied seasonally, there was little synchrony of bot activity among islands. Bot density was related negatively to rainfall but was not related to host density, suggesting that drier ambient conditions may promote reproduction by adult bot flies in this system.