Inhibition of cyclin-dependent kinase 5 but not of glycogen synthase kinase 3-ß prevents neurite retraction and tau hyperphosphorylation caused by secretable products of human T-cell leukemia virus type I-infected lymphocytes.

Human T-cell leukemia virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease characterized by selective loss of axons and myelin in the corticospinal tracts. This central axonopathy may originate from the impairment of anterograde axoplasmic transport. Previous work showed tau hyperphosphorylation at T(181) in cerebrospinal fluid of HAM/TSP patients. Similar hyperphosphorylation occurs in SH-SY5Y cells incubated with supernatant from MT-2 cells (HTLV-I-infected lymphocytes secreting viral proteins, including Tax) that produce neurite shortening. Tau phosphorylation at T(181) is attributable to glycogen synthase kinase 3-ß (GSK3-ß) and cyclin-dependent kinase 5 (CDK5) activation. Here we investigate whether neurite retraction in the SH-SY5Y model associates with concurrent changes in other tau hyperphosphorylable residues. Threonine 181 turned out to be the only tau hyperphosphorylated residue. We also evaluate the role of GSK3-ß and CDK5 in this process by using specific kinase inhibitors (LiCl, TDZD-8, and roscovitine). Changes in both GSK3-ß active and inactive forms were followed by measuring the regulatory phosphorylable sites (S(9) and Y(216) , inactivating and activating phosphorylation, respectively) together with changes in ß-catenin protein levels. Our results showed that LiCl and TDZD-8 were unable to prevent MT-2 supernatant-mediated neurite retraction and also that neither Y(216) nor S(9) phosphorylations were changed in GSK3-ß. Thus, GSK3-ß seems not to play a role in T(181) hyperphosphorylation. On the other hand, the CDK5 involvement in tau phosphorylation was confirmed by both the increase in its enzymatic activity and the absence of MT-2 neurite retraction in the presence of roscovitine or CDK5 siRNA transfection.

Leprosy

Leprosy remains an important health problem wordwide. The disease in caused by a chronic granulomatous infection of the skin and peripheral nerves with Mycobacterium leprae. The clinical range from tuberculoid to lepromatous leprosy is a result of variation in the cellular immune response to the mycobacterium. The resulting impairment of nerve fuinction causes be disabilities associated with leprosy. This review summarises recent advances in understanding of the biology of leprosy, clinical features of the disease, the current diagnostic criteria, and the new approaches to treatment of the infection and the immune-mediated complications. Supervesed multi-drug therapy (MDT) for fixed durations is highly effective for all forms of the disease. The widespread implemantation of MDT has been associated with a fall in the prevalence of the leprosy but as yet no reduction in the case-detection rate globally. Thus, leprosy control activities must be maintained for decades to interrupt transmission of infection

Segmental Necrotizing Granulomatous Neuritis of Leprosy

In leprosy, the occurrence of necrotizing nodular lesions in peripheral nerves is a relatively uncommon complication. Despite clinical and gross similarities, there are microscopical differences among groups of such cases, indicating that in all probability different pathogenetic mechanisms are operative. Furthermore, the vast majority of such cases are not true abscesses but are characterized by caseous necrosis and granulomatous inflammation. The traditional collective name [quot ]nerve abscess[quot ] is therefore inappropriate. Presented herein is an analytic study of 30 cases of the commonest variant, which we suggest should be called segmental necrotizing granulomatous neuritis of leprosy (SNGN). This lesion commonly affects the right ulnar nerve just above the elbow and occurs most often in those with the borderline tuberculoid form of leprosy. It appears to represent the result of a hypersensitivity phenomenon marked by a preponderance of epithelioid cells rather than a reaction of immunity in which lymphocytes predominate. Acid fast bacilli were demonstrable in the lesion in 77% of cases

Histaminoterapia en las neuritis leprosas

Los fenómenos subjetivos que acompañam a las neuritis leprosas, torturan cruelmente en ocasiones, a los enfermos. Inmerables tratamientos han sido preconizados: alcohol endovenoso, azul de metileno, toxinas de sepientes, ácico ósmico, inyecciones de adrenalina-efedrina, toxoide diftérico, métodos fisiorápicos, Vitamina B., histidina, histamina, etc. En general todos han dado más o menos buenos resultados, pero su efecto es parcial e incontante. La histamina ha sido empleada en dolores de otro origen, como en la ciática, reumatismo, úlcera gastro-duodenal. Se ha usado tambiém en dermatosis pruriginosas, en el zona, eczemas y dermatitis atópicas. Los resultados en todos estos casos, han sido variables. Las experiencias del autor se refierem al tratamiento y resultados comparativos, por medio de la histamina, histamina-policarpina y agua destilada, en 41 enfermos de lepra que sufríam de algias y otros fenómenos subjetivos que acompañan a las neutitis hansenianas. Las observaciones se extendieron a otros dos síntomas, a saber: infiltración edematoide de las extreminades y renitis