Amyloid beta protein 1-40 and 1-42 levels in matched cerebrospinal fluid and plasma from patients with Alzheimer disease.

We quantitated amyloid beta proteins 1-40 (Abeta40) and 1-42 (Abeta42), and alpha1- antichymotrypsin (ACT) in matched cerebrospinal fluid (CSF) and plasma of 50 patients with probable Alzheimer disease, and analyzed the relationships with age, sex, Mini-Mental State Examination (MMSE), and apolipoprotein E phenotype. There was no relation between CSF Abeta40 and Abeta42 levels with those of plasma. CSF and plasma Abeta40 and Abeta42 levels showed no association with age, sex, and MMSE score. There was a significant correlation between CSF ACT and plasma ACT levels. The data suggest that plasma ACT crosses the blood-brain barrier. However, a lack of correlation between CSF Abeta40 and Abeta42 levels with those of plasma suggests that Abeta in CSF and plasma originates from different sources.

[Transthyretin levels in serum and cerebrospinal fluid sustain the nutrio-viral hypothesis of the Cuban epidemic neuropathy]. / Niveles de transtirretina en suero y en líquido cefalorraquídeo apoyan la hipótesis nutrio-vírica de la neuropatía epidémica cubana.

INTRODUCTION: Transthyretin is considered an excellent marker for monitoring nutritional status in serum. In cerebrospinal fluid it is synthesized by chroroid plexus. Cuban epidemic neuropathy is an emergent disease with a hypothetically viral and nutritional origin. OBJECTIVE: To know the behavior of this transport molecule in serum and cerebrospinal fluid in patients with Cuban epidemic neuropathy. PATIENTS AND METHODS: Serum and cerebrospinal fluid was quantified in 11 patients with Cuban epidemic neuropathy, eight patients suffering from other neuropathies and 15 patients with Down's syndrome and 10 patients with Alzheimer's disease. RESULTS: Serum transthyretin was diminished in patients with Cuban epidemic neuropathy, other neuropathies and Alzheimer's disease. Down's syndrome patients had significantly higher transthyretin levels in comparison with Cuban epidemic neuropathy and Alzheimer's disease. Cerebrospinal fluid transthyretin was significantly increased in patients with Cuban epidemic neuropathy in comparison with the normal values and with Alzheimer's disease patients whose values were settled below the normal values. CONCLUSIONS: The decrement of serum transthyretin in Cuban epidemic neuropathy indicates malnutrition and its higher levels in cerebrospinal fluid also indicate a viral infection. These findings support the nutrio-viral hypothesis of the disease.

Alpha2 macroglobulin elevation without an acute phase response in depressed adults with Down's syndrome: implications.

Studies of immune function during depression in persons without intellectual disability (ID) have revealed elevated levels of alpha2 macroglobulin (alpha2M) and an acute phase protein (APP) response. Clinical observation suggests that people with Down's syndrome (DS) may have associated genetic abnormalities in their immune systems. The APP response and alpha2M changes in depressed versus non-depressed adults with DS was the subject of the present study. The serum pan-proteinase inhibitor alpha2M, and the AP proteins c-reactive protein (CRP), alpha1 antitrypsin (alpha1AT), ceruloplasmin (Cp), beta2 Macroglobulin (beta2M), transthyretin (Trans), serum amyloid protein (SAP), and albumin (Alb) were measured in 38 adults with DS, 19 of whom were diagnosed with and 19 without depression using a sandwich enzyme-linked immunosorbent assay (ELISA). The DSM-IV criteria were used for diagnoses. Medical and neurological examinations excluded medical disorders associated with APP response. Only alpha2M and CRP were significantly different in the depressed versus non-depressed groups. The alpha2M was higher, a response similar to one observed in depressed people without ID, but the CRP was lower in the depressed group, especially in those subjects not on psychotropic medications, contrary to the expected APP response to depression. The results suggest that alpha2M elevation in depressed adults with DS is independent of the APP response. An alternative explanation for its elevation is proposed linking the core symptom of depression with the mammalian dormancy/hibernation process. Further studies are needed to confirm that alpha2M elevation is specific to depression and that it might provide a helpful marker for the diagnosis of depression in people with ID.

Niveles de transtirretina en suero y en líquido cefalorraquídeoapoyan la hipótesis nutrio-vírica de la neuropatía epidémica cubana / Transthyretin levels in serum and cerebrospinal fluid supports nutrio-viral hypothesis of cuban epidemic neuropathy

Introducción. La transtirretina se considera un marcador excelente del estado nutricional en suero, y en el líquido cefalorraquídeo se sintetiza en los plexos coroides. La neuropatía epidémica cubana es una enfermedad emergente de origen hipotéticamente nutricional y vírico. Objetivo. Conocer el comportamiento de esta molécula de transporte en suero y líquido cefalorraquídeo en pacientes con neuropatía epidémica cubana. Pacientes y métodos. Se cuantifica la transtirretina por inmunodifusión radial en suero y líquido cefalorraquídeo de 11 pacientes con neuropatía epidémica cubana, ocho casos con neuropatías de otro tipo, 15 enfermos con síndrome de Down y 10 sujetos con enfermedad de Alzheimer. Resultados. Hay disminución de la transtirretina sérica en los pacientes con neuropatía epidémica cubana y con otras neuropatías, así como en los individuos que padecen enfermedad de Alzheimer. Los sujetos con síndrome de Down presentaron cifras elevadas significativamente en comparación con los pacientes de enfermedad de Alzheimer y neuropatía epidémica cubana. En líquido cefalorraquídeo, los valores de transtirretina en los casos de neuropatía epidémica cubana estuvieron elevados con respecto a los valores normales y con diferencias significativas respecto a los valores de los pacientes con enfermedad de Alzheimer, los cuales se situaron por debajo de las cifras normales. Conclusiones. En la neuropatía epidémica cubana, los valores disminuidos en suero de la transtirretina indican malnutrición, y las elevadas cifras en líquido cefalorraquídeo por la presencia de virus apoyan la hipótesis vírica de la enfermedad (AU)

Transmission of measles virus encephalitis to ferrets by intracardiac inoculation of a cell-associated SSPE virus strain.

Ferret fibroblasts infected with a cell-associated strain of subacute sclerosing panencephalitis virus were inoculated into the hearts of ferrets in order to study whether the virus can spread from the blood to the brain in this animal model. Five of 21 inoculated ferrets developed encephalitis 5-7 days later and were sacrificed. Sick animals showed inflammatory lesions in the brain, both perivascular cuffings and infiltration of inflammatory cells in the choroid plexus and meninges. Virus was isolated in cell cultures from various parts of the brain and virus antigen was found by immunostaining, particularly in the cortex. Virus was not detected in inflammatory cells by immunostaining but in situ hybridization with a cDNA probe demonstrated measles virus RNA in neurons and glia cells surrounding perivascular inflammatory cuffings and in a lymph node of one ferret. Ferrets inoculated into the heart with cell-associated SSPE virus seem to be a suitable animal model to study how the virus spreads from the blood to the brain.

Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides.

Lipids in fresh human milk do not inactivate viruses but become antiviral after storage of the milk for a few days at 4 or 23 degrees C. The appearance of antiviral activity depends on active milk lipases and correlates with the release of free fatty acids in the milk. A number of fatty acids which are normal components of milk lipids were tested against enveloped viruses, i.e., vesicular stomatitis virus, herpes simplex virus, and visna virus, and against a nonenveloped virus, poliovirus. Short-chain and long-chain saturated fatty acids had no or a very small antiviral effect at the highest concentrations tested. Medium-chain saturated and long-chain unsaturated fatty acids, on the other hand, were all highly active against the enveloped viruses, although the fatty acid concentration required for maximum viral inactivation varied by as much as 20-fold. Monoglycerides of these fatty acids were also highly antiviral, in some instances at a concentration 10 times lower than that of the free fatty acids. None of the fatty acids inactivated poliovirus. Antiviral fatty acids were found to affect the viral envelope, causing leakage and at higher concentrations, a complete disintegration of the envelope and the viral particles. They also caused disintegration of the plasma membranes of tissue culture cells resulting in cell lysis and death. The same phenomenon occurred in cell cultures incubated with stored antiviral human milk. The antimicrobial effect of human milk lipids in vitro is therefore most likely caused by disintegration of cellular and viral membranes by fatty acids. Studies are needed to establish whether human milk lipids have an antimicrobial effect in the stomach and intestines of infants and to determine what role, if any, they play in protecting infants against gastrointestinal infections.

Localization of measles virus antigens in subacute sclerosing panencephalitis in ferrets.

Young adult male ferrets were inoculated intracerebrally (i.c.) with a cell-associated encephalitogenic subacute sclerosing panencephalitis (SSPE) virus strain to study the pathogenesis of the disease at the ultrastructural level. Most became acutely ill in 8-13 days. Areas of the brain were examined with indirect immunoperoxidase labeling techniques to detect measles antigen. None of these animals showed the characteristic viral nucleocapsids or marked inflammatory response associated with SSPE. However, all had positive immunolabeling of unstructured virus antigen, especially in post-synaptic regions in all areas of the brain that were examined. One ferret, immunized with measles vaccine 40 days prior to challenge with SSPE, became ill 18 days post inoculation (p.i.). Perivascular cuffings of inflammatory cells and large cytoplasmic inclusions of fuzzy nucleocapsids were found in the brain and spinal cord. The study indicates that ferrets which become acutely ill after inoculation with cell-associated SSPE virus do so before there is a marked cellular immune response or formation of virus nucleocapsids.

Measles virus encephalitis in ferrets as a model for subacute sclerosing panencephalitis.

Young adult ferrets were used as experimental animals to study subacute sclerosing panencephalitis (SSPE). When cells infected with cell-associated measles virus strains isolated from SSPE patients were inoculated intracerebrally (i.c.) into ferrets, they developed an acute encephalitis and died within 1 to 3 weeks without detectable antibody formation. Immunization with live measles vaccine 5 weeks before i.c. inoculation changed the course of the infection in about 50% of the ferrets. These animals developed a subacute encephalitis within weeks or months after inoculation. Cell-associated measles virus was isolated from their brains and high measles antibody titers were found in their sera, comparable to those in sera of SSPE patients. Measles virus specific immunoglobulins (IgG) were present in their brains and determination of IgG/albumin ratios indicated that antibodies were synthesized in the brain in response to the persistent measles virus infection. Measles specific oligoclonal IgG bands were found in the sera and spinal fluids of these animals. Therefore, subacute ferret encephalitis has virological and immunological characteristics in common with SSPE, indicating that it may serve as a model for the human disease. Other animal models of SSPE are described briefly.

The emergence of antigenic variants is a rare event in long-term visna virus infection in vivo.

Six sheep persistently infected with visna virus were studied for 4 1/2 to 5 3/4 years until they became ill. Virus was isolated at intervals from peripheral blood leukocytes and cerebrospinal fluid (CSF), and at the time of sacrifice from various parts of the brain and the lungs. Both brain and lungs showed lesions typical of advanced visna/maedi. All the sheep formed antibodies in sera and CSF. Virus isolates from each sheep were tested in neutralization tests against sera and CSF collected from the same animal. In one sheep all isolates were found to be identical to the inoculated virus by this test. In each of the other sheep an antigenic variant emerged from 1 to 3 years after inoculation and remained in circulation even after the formation of autologous antibodies. In one case a variant was isolated from the lungs, whereas in all cases the virus isolated from the brain was identical to the inoculated virus. The results show that antigenic variants are rare in visna and do not seem to have a role in the pathogenesis of the disease.