Autophagy contributes to widespread neuronal degeneration in hamsters infected with the Echigo-1 strain of Creutzfeldt-Jakob disease and mice infected with the Fujisaki strain of Gerstmann-Sträussler-Scheinker (GSS) syndrome

The authors report here robust autophagy observed by electron microscopy in both the Echigo-1 strain of Creutzfeldt-Jakob disease in hamsters and the Fujisaki strain of Gerstmann-Str?ussler-Scheinker disease in mice. In both models, autophagic vacuoles were observed in several cellular compartments. In neuronal cell bodies, autophagic vacuoles of different size were seen. The cytoplasm of some neurons also contained semicircular cisterns equivalent to an early autophasophore. The major target of autophagy was dystrophic neurites, i.e., enlarged neuritic processes--mostly dendrites but also axonal terminals and preterminals. They contained numerous double- or multiple-membrane-bound autophagosomes or autophagolysosomes and large multivesicular bodies. Multivesicular bodies were also observed within autophagic vacuoles, and large multivesicular bodies were seen within synaptic terminals. Some dystrophic neurites was filled almost completely with multivesicular bodies; the latter were occasionally confluent. The authors conclude that autophagy is an important part of neuropathology in prion disease. They also suggest that spongiform vacuoles, a hallmark for the whole group of prion diseases, may in reality originate from autophagic vacuoles.     

Prion proteins with different conformations accumulate in Gerstmann-Sträussler-Scheinker disease caused by A117V and F198S mutations

Gerstmann-Str?ussler-Scheinker disease (GSS) is characterized by the accumulation of proteinase K (PK)-resistant prion protein fragments (PrP(sc)) of approximately 7 to 15 kd in the brain. Purified GSS amyloid is composed primarily of approximately 7-kd PrP peptides, whose N terminus corresponds to residues W(81) and G(88) to G(90) in patients with the A117V mutation and to residue W(81) in patients with the F198S mutation. The aim of this study was to characterize PrP in brain extracts, microsomal preparations, and purified fractions from A117V patients and to determine the N terminus of PrP(sc) species in both GSS A117V and F198S. In all GSS A117V patients, the approximately 7-kd PrP(sc) fragment isolated from nondigested and PK-digested samples had the major N terminus at residue G(88) and G(90), respectively. Conversely, in all patients with GSS F198S, an approximately 8-kd PrP(sc) fragment was isolated having the major N terminus start at residue G(74). It is possible that a further degradation of this fragment generates the amyloid subunit starting at W(81). The finding that patients with GSS A117V and F198S accumulate PrP(sc) fragments of different size and N-terminal sequence, suggests that these mutations generate two distinct PrP conformers.     

Naming ability in patients with mild to moderate Alzheimer's disease: what changes occur with the evolution of the disease?

OBJECTIVES:

Naming deficit is a linguistic symptom that appears in the initial phase of Alzheimer''s disease, but the types of naming errors and the ways in which this deficit changes over the course of the disease are unclear. We analyzed the performance of patients with Alzheimer''s disease on naming tasks during the mild and moderate phases and verified how this linguistic skill deteriorates over the course of the disease.

METHODS:

A reduced version of the Boston Naming Test was administered to 30 patients with mild Alzheimer''s disease, 30 patients with moderate Alzheimer''s disease and 30 healthy controls. Errors were classified as verbal semantic paraphasia, verbal phonemic paraphasia, no response (pure anomia), circumlocution, unrelated verbal paraphasia, visual errors or intrusion errors.

RESULTS:

The patients with moderate Alzheimer''s disease had significantly fewer correct answers than did both the control group and the group with mild Alzheimer''s disease. With regard to the pattern of errors, verbal semantic paraphasia errors were the most frequent errors in all three groups. Additionally, as the disease severity increased, there was an increase in the number of no-response errors (pure anomia). The group with moderate Alzheimer''s disease demonstrated a greater incidence of visual errors and unrelated verbal paraphasias compared with the other two groups and presented a more variable pattern of errors.

CONCLUSIONS:

Performance on nominative tasks worsened as the disease progressed in terms of both the quantity and the type of errors encountered. This result reflects impairment at different levels of linguistic processing.     

Modulation of immunity in mice with latent toxoplasmosis—the experimental support for the immunosuppression hypothesis of Toxoplasma-induced changes in reproduction of mice and humans

The immunosuppression hypothesis suggests that the increased sex ratio in mice and women with latent toxoplasmosis, retarded embryonic growth in the early phases of pregnancy, prolonged pregnancy of Toxoplasma-infected women, and increased prevalence of toxoplasmosis in mothers of children with Down syndrome can be explained by the presumed immunosuppressive effects of latent toxoplasmosis. Here, we searched for indices of immunosuppression in mice experimentally infected with Toxoplasma gondii. Our results showed that mice in the early phase of latent infection exhibited temporarily increased production of interleukin (IL)-12 and decreased production of IL-10. In accordance with the immunosuppression hypothesis, the mice showed decreased production of IL-2 and nitric oxide and decreased proliferation reaction (synthesis of DNA) in the mixed lymphocyte culture in the early and also in the late phases of latent toxoplasmosis. Since about 30% of the world population are latently infected by T. gondii, the toxoplasmosis-associated immunosuppression might have serious public health consequences.     

Catecholamines and their metabolites in the brain and urine of rats with experimental Parkinson’s disease

The content of catecholamines and their metabolites in the brain and the relationship between cerebral catecholamine levels and their urinary excretion were studied in rats with 6-OHDA-induced hemiparkinsonism. 6-OHDA reduced brain concentrations of dopamine, DOPAC, and homovanilic acid and urinary excretion of dopamine, dioxyphenilalanine, and DOPAC by more than 90%. A positive correlation was found between the concentrations of these metabolites in the urine and striatum. Measurement of urinary catecholamines and their metabolites is a perspective test for evaluating the status of the dopaminergic nigrosostriate system of the brain in experimental parkinsonism. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 223–227, August, 2000     

Coaxil (tianeptine) in the treatment of depression in Parkinson’s disease

An open, non-comparative clinical study was performed to assess the efficacy and safety of tianeptine (Coaxil) in Parkinson’s disease (PD). A total of 18 patients with PD were used whose clinical state increased moderately severe and more profound depression (assessed on the Hamilton and Beck scales). After three months of treatment, depression on the Hamilton depression scale was decreased by 34% and on the Beck scale by 31% compared with baseline data (_p < 0.05). Improvements in mental status were noted in 14 of 18 patients (77%); eight patients (44%) showed more than 50% reductions on the Hamilton scale. Analysis of the structure of depressive symptomatology showed that improvement occurred because of decreases in anxiety and the severity of somatoform symptoms and, to a lesser extent, in melancholy and sleep disturbance. There was no significant change in apathy. The decrease in the severity of depression was accompanied by an improvement in the quality of life. The efficacy of Coaxil was greater in patients with less marked depressive and motor symptoms, shorter durations of illness, and less marked cognitive impairments. Coaxil was well tolerated by the patients. The data obtained here provide grounds for recommending the use of Coaxil in the treatment of depression in PD. __________ Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 106, No. 3, pp. 20–25, March, 2006.     

Ultrastructural Study of the Osteointegration of Bioceramics (Whitlockite and Composite β-TCP + Collagen) in Rabbit Bone

Study examines the osteointegration of two porous ceramic implants, β-tricalcium phosphate (β-TCP) and a composite (β-TCP-collagen), in femur and tibias of 20 New Zealand white rabbits, which were sacrificed 1 week and 1, 4, and 12 months postimplant so that radiological, optical microscopic, and ultrastructural studies could be carried out. The results show a progressive degradation and resorption of both implant materials by means of a macrophagic reaction, which is at its most intense 1 month postimplant. The materials are substituted by newly formed bone tissue starting at the host bone-implant interface, the substitution being almost total by the end of the study, although less completely and earlier than in the case of the composite. Both materials can be considered as potential substitutes for bone tissue since they are biocompatible, bioreabsorbable, and osteogenic.     

Therapeutic Efficacy of the Neuroprotective Plant Adaptogen in Neurodegenerative Disease (Parkinson’s Disease as an Example)

Therapeutic efficacy of the plant neuroprotector Phytomix-40 in Parkinson’s disease was demonstrated. This preparation consists of the components from extracts of 40 plants, including some adaptogens (ginseng, eleutherococcus, Rhodiola rosea, etc.). The preparation normalized immune, antioxidant, and hormonal parameters in patients. The neuroprotective plant adaptogen can be used in complex therapy for Parkinson’s disease for improving its efficacy.     

Efficacy and safety of choline alphoscerate (cereton) in patients with parkinson’s disease with cognitive impairments

An open 10-day study in which the therapeutic actions of Cereton were compared with those of piracetam was performed. Cereton was used in 40 patients (experimental group) at a dose of 1000 mg, while piracetam was used in 20 patients at a dose of 2000 mg; both agents were given as intravenous infusions in 200 ml of physiological saline on the background of antiparkinsonism agents. Patients’ status was evaluated using a complex of psychometric scales and neuropsychological tests, along with tools to assess the severity of the main symptoms of parkinsonism, side effects, and quality of life. Use of Cereton produced marked and moderate improvements in the state of cognitive functions more frequently than piracetam (40% and 25%, respectively), while the incidence of deterioration was lower (5% and 15%, p < 0.05). Cereton was very well tolerated by the patients: brief and short-term side effects were seen in only six patients (15%).     

Tumor Necrosis Factor (TNF-��) and C-reactive Protein (CRP) are Positively Associated with the Risk of Chronic Kidney Disease in Patients with Type 2 Diabetes

Purpose

Chronic low-grade inflammation may induce chronic kidney disease in patients with type 2 diabetes. This study investigated the relation between inflammatory biomarkers and chronic kidney disease in patients with type 2 diabetes, which has not yet been reported in Asian populations.

Materials and Methods

A cross-sectional study was performed in 543 patients recruited from diabetic clinics for an ongoing, prospective study. Multivariate logistic regression was used to evaluate the association between inflammatory biomarkers and the presence of chronic kidney disease (estimated glomerular filtration rate < 60 mL/min per 1.73 m² by the simplified Modification of Diet in Renal Disease equation using plasma creatinine).

Results

The risk of chronic kidney disease increased in the highest quartiles of C-reactive protein (CRP) [multivariate odds ratio (OR) = 3.73; 95% CI = 1.19-1.70] and tumor necrosis factor-α (multivariate OR = 4.45; 95% CI = 1.63-12.11) compared to the lowest quartiles after adjustments for age, sex, zinc intake, and other putative risk factors for chronic kidney disease.

Conclusion

Our results suggest that CRP and tumor necrosis factor-α may be independent risk factors for chronic kidney disease in patients with type 2 diabetes. A causal mechanism of this association should be evaluated in a follow-up study of Korean patients with type 2 diabetes.     

Intergenerational changes in birth parameters in Kraków (Poland) in the context of socio-economic transformation from 1985–2010

Background: Analyses of birth parameters worldwide reveal relatively high variability over time, often related to socioeconomic factors.

Aim: The aim was to determine the existence of inter-generational changes in birth parameters in Kraków (Poland) in recent years and factors responsible.

Subjects and methods: This research analysed data on 7800 newborns (e.g. body length and weight) and their parents in the years 1985–2010. The significance of differences was calculated using ANOVA. To examine the potential effect of environmental factors, MANOVA were used.

Results: In the case of birth weight no significant changes were observed. A significant decreasing tendency in birth length from the beginning of the 21st century was shown – this observation is quite rare. Accordingly, BMI increased significantly in the 2000s. A decreasing tendency was observed for head circumference.

Conclusion: In the analysed period Poland experienced significant socio-economic changes, which could have partly contributed to the observed changes. Some of the observed trends in birth parameters are recent phenomena and it seems necessary to continue the research to confirm if these changes form a steady trend or are only temporary. Tracking any phenomena related to the development is important for the determination of disruptive factors and the reduction of their adverse effects.     

Is the content of guidelines/pathways a barrier for the integration of palliative Care in Chronic Heart Failure (CHF) and chronic pulmonary obstructive disease (COPD)? A comparison with the case of cancer in Europe

Background

There is a notable inequity in access to palliative care (PC) services between cancer and Chronic Heart Failure (CHF)/Chronic Obstructive Pulmonary Disease (COPD) patients which also translates into discrepancies in the level of integration of PC. By cross-examining the levels of PC integration in published guidelines/pathways for CHF/COPD and cancer in Europe, this study examines whether these discrepancies may be attributed to the content of the guidelines.

Design

A quantitative evaluation was made between integrated PC in published guidelines for cancer and CHF/COPD in Europe. The content of integrated PC in guidelines/pathways was measured using an 11 point integrated PC criteria tool (IPC criteria). A statistical analysis was carried out to detect similarities and differences in the level of integrated PC between the two groups.

Results

The levels of integration between CHF/COPD and cancer guidelines/pathways have been shown to be statistically similar. Moreover, the quality of evidence utilized and the date of development of the guidelines/pathways appear not to impact upon the PC integration in the guidelines.

Conclusion

In Europe, the empirically observed imbalance in integration of PC for patients with cancer and CHF/COPD may only partially be attributed to the content of the guidelines/pathways that are utilized for the PC implementation. Given the similarities detected between cancer and CHF/COPD, other barriers appear to play a more prominent role.

     

The concept of structured treatment interruptions in the management of patients with human immunodeficiency virus (HIV) disease: where are we currently?

The failure to achieve viral eradication with currently available antiretroviral agents has spawned new approaches to limiting drug exposure. Highly active antiretroviral therapy (HAART) lowers morbidity and mortality of HIV disease but cannot eradicate the virus from the body. Structured treatment interruptions (STIs) have been proposed as a strategy to minimize the toxicities of HAART while providing a mechanism to enhance HIV-specific immunity. STIs have been investigated in three distinct clinical scenarios: during acute infection, during chronic infection, and during virologic failure. However, many questions still need to be answered in controlled trials before STIs can be adopted in clinical practice.     

Activity of the cyclic depsipeptide emodepside (BAY 44–4400) against larval and adult stages of nematodes in rodents and the influence on worm survival

The present investigations deal with the activity of the cyclic depsipeptide emodepside (BAY 44-4400) against larval and adult stages of three rodent nematodes. While emodepside acts strongly against the adult stages of the rat nematodes Nippostrongylus brasiliensis and Strongyloides ratti, as well as against the mouse nematode Heligmosomoides polygyrus, its actions against the larval stages of these nematodes vary according to the species. Thus, emodepside is highly effective against the lung and intestine larval stages of N. brasiliensis and S. ratti. By contrast. the larval stages of H. polygyrus in the intestine are only partly affected by higher emodepside dosages.