Chondroitin sulfate inhibits lipopolysaccharide-induced inflammation in rat astrocytes by preventing nuclear factor kappa B activation.

Chondroitin sulfate (CS) is a glucosaminoglycan (GAG) currently used for the treatment of osteoarthritis because of its antiinflammatory and antiapoptotic actions. Recent evidence has revealed that those peripheral effects of CS may also have therapeutic interest in diseases of the CNS. Since neuroinflammation has been implicated in different neuronal pathologies, this study was planned to investigate how CS could modulate the inflammatory response in the CNS by using rat astrocyte cultures stimulated with lipopolysaccharide (LPS). We have evaluated different proteins implicated in the nuclear factor kappa B (NFkappaB) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways employing RT-PCR, western blot and immunofluorescence techniques. At 10 microM, CS prevented translocation of p65 to the nucleus, reduced tumour necrosis factor alpha (TNF-alpha) mRNA and mitigated cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) induction by LPS. However, it did not modify LPS-induced IP-10 and SOCS-1 mRNA, proteins that participate in the JAK/STAT pathway. The results of this study indicate that CS can potentially reduce neuroinflammation by inhibition of NFkappaB. Therefore endogenous GAGs could afford neuroimmunomodulatory actions under neurotoxic conditions.

Two novel CLN5 mutations in a Portuguese patient with vLINCL: insights into molecular mechanisms of CLN5 deficiency.

The neuronal ceroid-lipofuscinoses are the most common neurodegenerative disorders in childhood characterized by progressive blindness, epilepsy, brain atrophy, and premature death. Based on the age at onset, disease progression and ultrastructural features three classical (infantile, late-infantile, and juvenile) and three variant late-infantile forms are generally distinguished (Finnish variant, Costa Rican variant, and epilepsy with progressive motor retardation). The Finnish variant late-infantile form has been associated with CLN5 gene defects, with only five mutations described to date. We report a patient with vLINCL/CLN5 who represents the first evidence of the disease in the Portuguese population. Mutational screening revealed the previously described missense mutation c.835G>A (D279N) inherited from the mother, and two novel mutations, c.565C>T (Q189X) and c.335G>C (R112P) from paternal and maternal inheritance, respectively. Based on data here reported: (i) the number of possible mutations in CLN5 gene is now 7; (ii) the CLN5 Portuguese case represents the third description of the disease outside northern Europe; (iii) the CLN5/mRNA expression level reduced to 45% supports the existence of one mRNA non-producing allele, further noticeable at the protein level; (iv) Western blotting data using a specific antibody to human CLN5p provided evidence for the presence of four integral membrane isoforms in human fibroblasts; (v) data from differential expression of CLN2, CLN3, and CLN5 suggest down-regulation of CLN3 gene expression in CLN2 and CLN5-deficient human patients and this observation strengths the hypothesis of functional redundancy of the CLN system.

[Treatment of racemose neurocysticercosis of the spine]. / Tratamiento de la neurocisticercosis racemosa medular.

INTRODUCTION: Neurocysticercosis (NCC) is the most frequent parasitic infection of the central nervous system, and its prevalence is high in Portugal. Spinal involvement is rare, only occurring in between 1 and 5% of cases, and causes many problems when it comes to its diagnosis and treatment. Spinal leptomeningeal NCC is particularly difficult to treat, especially if associated to arachnoiditis. We report a case of NCC with spinal leptomeningeal involvement associated to extensive arachnoiditis, in which the therapeutic measures we have available today were totally ineffective. CASE REPORT: We describe the case of a 37-year-old male from Cape Verde, who was kept under surveillance because of a 3-month history of symptoms of cauda equina syndrome. In the last few months he also complained of holocranial headaches. Magnetic resonance (MR) imaging showed numerous cystic lesions in the bottom of the thecal sac, associated to extensive arachnoiditis, and MR images of the brain revealed compensated hydrocephalus. Diagnosis of NCC was confirmed by positive immunoblot in serum and in cerebrospinal fluid (CSF). Following insertion of a ventriculoperitoneal shunt, the patient received treatment with albendazole and corticoids for two weeks, and showed a clinical improvement. One year later, he showed symptoms of acute tetraparesis, and a cervical MRI showed cystic lesions with spinal cord compression and intense arachnoiditis. In spite of a decompression laminectomy, with removal of the cysts, and therapy with praziquantel and corticoids, the patient's clinical status did not improve. CONCLUSIONS: Spinal racemose NCC associated to arachnoiditis has a poor prognosis and is often untreatable. The therapeutic options in NCC of the spine are discussed, and attention is drawn to the importance of cysticercotic arachnoiditis in the prognosis of the disease.

Tratamiento de la neurocisticercosis racemosa medular / Treatment of racemose neurocysticercosis of the spine

Introducción. La neurocisticercosis (NCC) es la infección parasitaria más frecuente del sistema nervioso central y cuenta con una elevada prevalencia en Portugal. La afectación medular es rara, se produce tan sólo entre el 1 y el 5% de los casos, y su diagnóstico y tratamiento ocasiona muchas dificultades. La NCC leptomeníngea medular es particularmente difícil de tratar, especialmente si se asocia a aracnoiditis. Describimos un caso de NCC con afectación leptomeníngea medular asociada a una extensa aracnoiditis, y en la cual las medidas terapéuticas de las que se dispone en la actualidad resultaron ineficaces. Caso clínico. Varón de 37 años, natural de Cabo Verde, al que se sometió a observación por presentar un cuadro de síndrome de cauda equina con progresión desde hacía tres meses. En los últimos meses se quejaba también de cefaleas holocraneales. La RM puso de manifiesto múltiples lesiones quísticas en el fondo del saco tecal, asociadas a una extensa aracnoiditis, y la RM encefálica reveló una hidrocefalia compensada. El diagnóstico de NCC se confirmó por inmunoelectrotransferencia en el suero y en el líquido cefalorraquídeo. Se le colocó una derivación ventriculoperitoneal, se le suministró albendazol y corticoides durante dos semanas, y experimentó una mejoría clínica. Un año después, presentó un cuadro de tetraparesia aguda, y la RM cervical mostró lesiones quísticas con compresión medular y aracnoiditis intensa. A pesar de la laminectomía descomprensiva con extirpación de los quistes, y la terapia con pracicuantel y corticoides, no se produjo ninguna mejoría en su estado clínico. Conclusiones. La NCC racemosa medular asociada a aracnoiditis presenta un mal pronóstico y es frecuentemente intratable. Se discuten las opciones terapéuticas en la NCC medular y se señala la importancia de la aracnoiditis cisticercótica en el pronóstico de la enfermedad

Introduction. Neurocysticercosis (NCC) is the most frequent parasitic infection of the central nervous system, and its prevalence is high in Portugal. Spinal involvement is rare, only occurring in between 1 and 5% of cases, and causes many problems when it comes to its diagnosis and treatment. Spinal leptomeningeal NCC is particularly difficult to treat, especially if associated to arachnoiditis. We report a case of NCC with spinal leptomeningeal involvement associated to extensive arachnoiditis, in which the therapeutic measures we have available today were totally ineffective. Case report. We describe the case of a 37-year-old male from Cape Verde, who was kept under surveillance because of a 3-month history of symptoms of cauda equina syndrome. In the last few months he also complained of holocranial headaches. Magnetic resonance (MR) imaging showed numerous cystic lesions in the bottom of the thecal sac, associated to extensive arachnoiditis, and MR images of the brain revealed compensated hydrocephalus. Diagnosis of NCC was confirmed by positive immunoblot in serum and in cerebrospinal fluid (CSF). Following insertion of a ventriculoperitoneal shunt, the patient received treatment with albendazole and corticoids for two weeks, and showed a clinical improvement. One year later, he showed symptoms of acute tetraparesis, and a cervical MRI showed cystic lesions with spinal cord compression and intense arachnoiditis. In spite of a decompression laminectomy, with removal of the cysts, and therapy with praziquantel and corticoids, the patient’s clinical status did not improve. Conclusions. Spinal racemose NCC associated to arachnoiditis has a poor prognosis and is often un-treatable. The therapeutic options in NCC of the spine are discussed, and attention is drawn to the importance of cysticercotic arachnoiditis in the prognosis of the disease

3-Hydroxybutyrate co-infused with noradrenaline decreases resulting plasma levels of noradrenaline in Wistar rats.

Pentobarbital-anaesthetized male Wistar rats were infused with 6microgkg-1min-1 of noradrenaline. The infusion was supplemented with 8.5 mgkg-1min-1 of D-3-hydroxybutyrate (3-OHB) for 15 min in order to determine its effect on the adrenergic response of the rat. Plasma levels of noradrenaline rose to a plateau of approximately 50 nmoll-1 with infusion. In the group infused with noradrenaline alone, noradrenaline levels were maintained for 1h. Supplementation with 3-OHB induced a decrease in plasma noradrenaline level that was inversely correlated with 3-OHB level. Aortic and interscapular brown adipose tissue temperatures increased with noradrenaline infusion, but the rise was arrested by 3-OHB; replacing 3-OHB with glucose had no effect. Infusion of saline, glucose or 3-OHB in the absence of noradrenaline did not induce a rise in temperature in either tissue. Blood 3-OHB concentration increased to 1.2 mmoll-1 during 3-OHB infusion, decreasing rapidly at the end of infusion. Blood glucose levels increased with noradrenaline infusion; the presence of high 3-OHB levels decreased glucose concentration. The effects observed were transient and dependent on 3-OHB concentration; these effects may help explain most of the other effects of noradrenaline described here. The role of 3-OHB as a regulator of adrenergic responses seems to be part of a complex fail-safe mechanism which prevents wasting.