Live viral vaccines in patients with partial DiGeorge syndrome: clinical experience and cellular immunity

Partial DiGeorge syndrome (pDGS) is an inherited primary immunodeficiency syndrome (incidence, 1:3000 live births) primarily affecting cellular immune function; partial, infers thymic hypoplasia with detectable circulating T-lymphocytes and adequate function. No guidelines exist regarding the recommendations for use of live viral vaccines (LVVs) in this extensive population of pediatric patients. We reviewed the experience with live viral vaccines in our cohort of patients with pDGS. Of 53 patients, 25 (47%) had received a live viral vaccine. No significant adverse events were recorded in association with administration of live viral vaccines. There was no statistically significant difference between cellular immune function at initial presentation between those patients that received live viral vaccines and those that did not. Adequate cellular immune function was documented for 15 of the 25 LVV recipients at the time of vaccine administration without significant change from baseline. These observations suggest that live viral vaccines appear safe in patients with pDGS and stable immune function.     

Guillain-Barré syndrome in patients treated for Hodgkin disease

INTRODUCTION: A 14-year-old boy treated with Hodgkin's disease developed muscular weakness and pain, hypotonia, abolished deep tendon reflexes. Examination of the cerebrospinal fluid showed albuminocytologic dissociation, the characteristic finding of Guillain-Barré syndrome. After high dose steroid treatment complete recovery occurred. DISCUSSION: Paraneoplastic neuropathies may develop in patients with cancer, Guillain-Barré syndrome occurs in patients with active Hodgkin's disease. CONCLUSIONS: Progressive neurological signs may indicate the presence of a malignancy, or in case of chemotherapy shows the activity of the tumour.     

Neurotoxic effects of subchronic intratracheal Mn nanoparticle exposure alone and in combination with other welding fume metals in rats

Manganese (Mn) is a toxic heavy metal exposing workers in various occupational settings and causing, among others, nervous system damage. Metal fumes of welding, a typical source of Mn exposure, contain a complex mixture of metal oxides partly in nanoparticle form. As toxic effects of complex substances cannot be sufficiently understood by examining its components separately, general toxicity and functional neurotoxicity of a main pathogenic welding fume metal, Mn, was examined alone and combined with iron (Fe) and chromium (Cr), also frequently found in fumes. Oxide nanoparticles of Mn, Mn?+?Fe, Mn?+?Cr and the triple combination were applied, in aqueous suspension, to the trachea of young adult Wistar rats for 4?weeks. The decrease of body weight gain during treatment, caused by Mn, was counteracted by Fe, but not Cr. At the end of treatment, spontaneous and evoked cortical electrical activity was recorded. Mn caused a shift to higher frequencies, and lengthened evoked potential latency, which were also strongly diminished by co-application of Fe only. The interaction of the metals seen in body weight gain and cortical activity were not related to the measured blood and brain metal levels. Fe might have initiated protective, e.g. antioxidant, mechanisms with a more general effect.     

Nasal Administration of Cationic Nanoemulsions as Nucleic Acids Delivery Systems Aiming at Mucopolysaccharidosis Type I Gene Therapy

Purpose

This study demonstrates the nasal administration (NA) of nanoemulsions complexed with the plasmid encoding for IDUA protein (pIDUA) as an attempt to reach the brain aiming at MPS I gene therapy.

Methods

Formulations composed of DOPE, DOTAP, MCT (NE), and DSPE-PEG (NE-PEG) were prepared by high-pressure homogenization, and assessed in vitro on human fibroblasts from MPS I patients and in vivo on MPS I mice for IDUA production and gene expression.

Results

The physicochemical results showed that the presence of DSPE-PEG in the formulations led to smaller and more stable droplets even when submitted to dilution in simulated nasal medium (SNM). In vitro assays showed that pIDUA/NE-PEG complexes were internalized by cells, and led to a 5% significant increase in IDUA activity, besides promoting a two-fold increase in IDUA expression. The NA of pIDUA/NE-PEG complexes to MPS I mice demonstrated the ability to reach the brain, promoting increased IDUA activity and expression in this tissue, as well as in kidney and spleen tissues after treatment. An increase in serum IL-6 was observed after treatment, although with no signs of tissue inflammatory infiltrate according to histopathology and CD68 assessments.

Conclusions

These findings demonstrated that pIDUA/NE-PEG complexes could efficiently increase IDUA activity in vitro and in vivo after NA, and represent a potential treatment for the neurological impairment present in MPS I patients.

     

Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by NMSO3 in tissue culture assays

Human metapneumovirus (hMPV) is a recently elucidated respiratory virus pathogen for which there are no agents currently licensed to prevent or treat infections caused by it. However, NMSO3 has been reported to inhibit replication of human respiratory syncytial virus (hRSV), a virus that is closely related to hMPV, both in vitro in tissue culture cells and in vivo in cotton rats. For this reason, experiments were performed to compare the antiviral activity of NMSO3 against both hRSV and hMPV in tissue culture-based assays. Heparin and ribavirin, two other compounds known to inhibit hRSV, and two other paramyxoviruses, human parainfluenza virus type 3 (PIV3) and measles virus (MV), were included in these tests for comparison. All three compounds significantly inhibited the replication of subtype A and B strains of hRSV and serotypes 1 and 2 hMPV. However, unlike ribavirin, NMSO3 and heparin inhibited only hMPV and hRSV and not PIV3 or MV. Also unlike ribavirin, the activity of the two sulfated molecules was most effective if these materials were present during virus attachment and penetration of host cells. Interestingly, NMSO3, but not heparin, was able to limit secondary infection and spread of both viruses.     

Assessment of lunch served in the Workers' Food Program, Brazil

OBJECTIVE: In the light of the Workers' Food Program (WFP) growth and its recent review of nutritional parameters regulations, the study aimed at evaluating food intake in WFP through dietary assessment of lunch served in the program and workers' nutritional status. METHODS: A cross-sectional study was carried out in a representative sample of workers in Brasilia, Federal District, Brazil. A total of 1,044 subjects who had lunch at 52 food and nutrition units were evaluated. Social-economic and demographic data were collected as well as anthropometric measures for calculating the Body Mass Index. Food intake was assessed by dish weight and direct observation of dish composition. RESULTS: Of all subjects, 43% had excess weight, 33.7% were overweight and 9.3% were obese. Males were most affected. Median lunch energy intake was 515 kcal in women and 736 kcal in men. Median dietary fiber intake was 6.0 g among women and 8.3 g among men, and median cholesterol intake was over 90 mg among subjects with excess weight. CONCLUSIONS: The results indicate that the study population who is often seen as healthy is at nutritional risk. Workers in WFP should be targeted for health promotion strategies using especially nutritionists' skills as educators.     

Regulatory role of capsaicin-sensitive peptidergic sensory nerves in the proteoglycan-induced autoimmune arthritis model of the mouse

Objective

The regulatory role of capsaicin-sensitive peptidergic sensory nerves has been shown in acute inflammation, but little is known about their involvement in T/B-cell driven autoimmune arthritis. This study integratively characterized the function of these nerve endings in the proteoglycan-induced chronic arthritis (PGIA), a translational model of rheumatoid arthritis.

Methods

Peptidergic afferents were defunctionalized by resiniferatoxin (RTX) pretreatment in BALB/c mice, PGIA was induced by repeated antigen challenges. Hind paw volume, arthritis severity, grasping ability and the mechanonociceptive threshold were monitored during the 17-week experiment. Myeloperoxidase activity, vascular leakage and bone turnover were evaluated by in vivo optical imaging. Bone morphology was assessed using micro-CT, the intertarsal small joints were processed for histopathological analysis.

Results

Following desensitization of the capsaicin-sensitive afferents, ankle edema, arthritis severity and mechanical hyperalgesia were markedly diminished. Myeloperoxidase activity was lower in the early, but increased in the late phase, whilst plasma leakage and bone turnover were not altered. Desensitized mice displayed similar bone spurs and erosions, but increased trabecular thickness of the tibia and bony ankylosis of the spine. Intertarsal cartilage thickness was not altered in the model, but desensitization increased this parameter in both the non-arthritic and arthritic groups.

Conclusion

This is the first integrative in vivo functional and morphological characterization of the PGIA mouse model, wherein peptidergic afferents have an important regulatory function. Their overall effect is proinflammatory by increasing acute inflammation, immune cell activity and pain. Meanwhile, their activation decreases spinal ankylosis, arthritis-induced altered trabecularity, and cartilage thickness in small joints.

     

Levetiracetam reduces myoclonus in corticobasal degeneration: report of two cases

Levetiracetam (LEV) has been shown to suppress myoclonus of various origins. Corticobasal degeneration (CBD), a progressive neurodegenerative disorder with Parkinsonian syndrome, is frequently accompanied by myoclonus. We investigated the effect of LEV on myoclonus in two CBD patients. LEV remarkably decreased the myoclonic activity in both patients already at 1,500 mg/day dose. This is the first report on LEV alleviating myoclonus in CBD. Our data indicate that it might be worthwhile to assess this effect in an appropriately designed study.     

Bcl-2 or Bcl-XL gene therapy reduces apoptosis and increases plasticity protein GAP-43 in PC12 cells

The anti-apoptotic gene replacement could be an option in preventing hypoxia induced neuronal loss—necrosis and/or apoptosis. This intervention is however still controversial. In this paper, we tested the bcl-2 or bcl-XL anti-apoptotic gene transfers using an adenovirus vector in PC12 cells after hypoxia and re-oxygenation. Gene delivery results in a significant increase in both Bcl-2 and Bcl-XL proteins expression. Hypoxia (1 h)/re-oxygenation (4–48 h) have a detrimental effect upon cultured cells by inducing increased apoptosis by 30% compared to the controls. After hypoxia the compromised mitochondrial membrane function was detected by decreased tetramethyl-rhodamine-ethylester (TMRE) staining. Anti-apoptotic genes transferred 1 h after hypoxia, prevent the cell damage; the number of apoptotic cells has been reduced significantly and the gene transfers prevent mitochondrial membrane damage. Under normoxic conditions or following hypoxia the expression of plasticity protein, growth associated protein 43 (GAP-43) increased significantly by the gene treatment. We can conclude that anti-apoptotic gene transfers are not only cytoprotective as it is already documented before but these genes activate GAP-43 as well. This link on apoptotic signals and cell plasticity is a new finding.