Enrique R. Marschoff

Parkinson's disease is associated with oxidative stress: comparison of peripheral antioxidant profiles in living Parkinson's, Alzheimer's and vascular dementia patients

Summary. Antioxidant profiles in Parkinsons disease (PD; n = 15), dementias of Alzheimers type (DAT; 18) and Vascular (VD; 15), and control subjects (C; 14) were studied. Cu-Zn superoxide dismutase (SOD), catalase (CAT), glutathione system (GLU) and thiobarbituric acid reactive substances (TBARS) were measured in erythrocytes; antioxidant capacity (TRAP) in plasma. Biochemical variables were analyzed simultaneously using multivariate and non-parametric methods. Clinical diagnostic resulted associated with the main source of variability in antioxidant variables (Kruskal-Wallis: H = 32.58, p = 0.000001). Comparison of PD and C resulted highly significant (z = 4.47, p = 0.000047), demonstrating an association between oxidative stress and PD. SOD and TBARS were significantly higher in pathological groups against C (p = 0.0000001, p = 0.051); TRAP resulted lower (p = 0.00015). Discriminant functions constructed using biochemical variables separated pathological groups (93% success) from C, and DAT (88.9%) from VD (73.3%); but not PD from DAT or VD. Antioxidant profiles of PD patients showed characteristics overlapping with DAT (60%) and with VD (40%), suggesting biochemical similarities between them.

The antioxidant enzymatic blood profile in Alzheimer's and vascular diseases. Their association and a possible assay to differentiate demented subjects and controls

A study of several elements of the antioxidative system: Cu-Zn superoxide dismutase (SOD), catalase (CAT), glutathione system (GLU), chemiluminescence (CHE), and antioxidant capacity (AOX), was conducted in 20 demented probable Alzheimers (DAT), and 15 vascular demented (VD) patients, 19 control (C) subjects, and 11 relatives (F) of one DAT patient. A significant association was found between the variables of the antioxidant system, measured in blood samples, and the neurological pathologies VD and DAT: Kruskal-Wallis test; p = 0.0006 (p = 0.014 when the analysis did not include SOD). This demonstrated that VD and DAT diseases are accompanied by oxidative disorders. The VD and DAT diseases are differentially distinguishable by changes in blood profiles. A graphical method for classification, the Principal Components Analysis (PCA), distinguished between demented and non-demented subjects on the basis of their laboratory variables. A numerical method, Discriminant Functions (DF), constructed to separate the clinical groups on the basis of the same variables, obtained relatively high percentages of success: 92% of demented were detected against healthy subjects; of the latter 82% have been correctly identified as non-demented. Discrimination between VD and DAT patients was achieved for 100% of VD and 86% of DAT patients. DF were similarly successful in detecting the healthy condition of DAT relatives. Possible different mechanisms involved in H2O2 elimination in DAT and VD patients are proposed, where CAT is the responsible enzyme of this reaction in DAT patients, while in VD this function would be achieved mainly through the action of GLU. It seems that SOD levels are stable, at least, within one year. Variations appear to be linked with clinical changes.

Oxidative stress in Alzheimer's and vascular dementias: masking of the antioxidant profiles by a concomitant Type II diabetes mellitus condition

Oxidative stress is associated with Alzheimers (DAT) and vascular (VD) dementias, as well as Type II diabetes mellitus (DIAB) and affected by hypoglycemic therapy. The population (n = 122; males = 60; mean age = 72.57 +/- 7.06) consisted of controls (CTR), DAT and VD patients, with (DAT + DIAB, VD + DIAB) and without concomitant DIAB, resulting in six groups where the antioxidant profile was determined: copper-zinc superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), and total antioxidant capacity (TRAP). The results were analyzed using a two-way ANOVA design and Bonferroni statistic. The ANOVAs yielded significant differences between groups for all components of the profile: SOD, p = 0.00000006; TBARS, p = 0.0000012; TRAP, p = 0.0000003. The significance level for comparisons between groups was set at alpha = 0.05. The comparisons DIAB vs. CTR, DAT+DIAB vs. DAT, and DIAB demented vs. DIAB non-demented resulted significant for all variables. VD + DIAB vs. VD resulted significant for all variables except TRAP. The antioxidant profiles of DIAB and CTR are different. The differences cannot be directly related with what is observed in dementias. The differences in profiles of demented and non-demented are somewhat hidden when demented patients are affected by a concomitant DIAB condition and/or hypoglycemic treatment, thus conditioning the diagnostic value for dementias of the profiles.

Enfermedad de Alzheimer y deterioro cognitivo asociado a la diabetes mellitus de tipo 2: relaciones e hipótesis

INTRODUCTION Epidemiological studies have demonstrated that patients with diabetes mellitus have an increased risk of developing Alzheimer disease, but the relationship between the 2 entities is not clear. DEVELOPMENT Both diseases exhibit similar metabolic abnormalities: disordered glucose metabolism, abnormal insulin receptor signalling and insulin resistance, oxidative stress, and structural abnormalities in proteins and β-amyloid deposits. Different hypotheses have emerged from experimental work in the last two decades. One of the most comprehensive relates the microvascular damage in diabetic polyneuritis with the central nervous system changes occurring in Alzheimer disease. Another hypothesis considers that cognitive impairment in both diabetes and Alzheimer disease is linked to a state of systemic oxidative stress. Recently, attenuation of cognitive impairment and normalisation of values in biochemical markers for oxidative stress were found in patients with Alzheimer disease and concomitant diabetes. Antidiabetic drugs may have a beneficial effect on glycolysis and its end products, and on other metabolic alterations. CONCLUSIONS Diabetic patients are at increased risk for developing Alzheimer disease, but paradoxically, their biochemical alterations and cognitive impairment are less pronounced than in groups of dementia patients without diabetes. A deeper understanding of interactions between the pathogenic processes of both entities may lead to new therapeutic strategies that would slow or halt the progression of impairment.

Insulin, glucose and glycated hemoglobin in Alzheimer’s and vascular dementia with and without superimposed Type II diabetes mellitus condition

Summary.Increased concentrations of insulin, glucose and glycohemoglobin are associated with Type II diabetes mellitus (DM) and recognized as characteristic markers of the disease; in Alzheimer’s (AD), Vascular dementia (VaD), and both dementia’s with superimposed diabetes (AD + DM, VaD + DM) the knowledge is scarce. The sample (n = 122; males = 60; mean age = 73 ± 7) comprised DM, AD, VaD, AD + DM, and VaD + DM patients, and healthy controls (C). The ANOVA’s yielded significant differences between groups: Insulin p = 3.7 × 10−3; Glucose p < 10−12; Glycohemoglobin p = 9.2×10−4. Comparisons between groups (DM vs. C, AD + DM vs. AD, VaD + DM vs. VaD, and demented DM vs. non-demented DM) resulted significant for all variables (Bonferroni’s statistic, α = 0.05). Diabetic and diabetic demented patients presented significant increases largely different from controls (0.01 < p < 0.001), unlike the non-significant changes in their non-diabetic counterparts; linear relationships were found across all groups. The correlation’s insulin/glucose and insulin/glycohemoglobin change to positive within demented groups, indicating a different performance of insulin in demented and non-demented subjects.

Comparison of the determination of superoxide dismutase and antioxidant capacity in neurological patients using two different procedures

As oxidative stress in relation with neurological diseases has become an important point in recent research, simple methods to be used in epidemiological studies and clinical practice are required. The hypothesis that the analytical methods used in research laboratories (RLM) can be used interchangeably with commercial kits (CKM) for SOD and TRAP is tested. Both methods were compared using linear transformations of the RLM measurements into the CKM scales. Data were obtained from Alzheimers, Parkinsons, and vascular dementia patients and controls. The lack of fit and the runs test of residuals were not significant, but the same sign method detected significant nonlinearities (P<0.000001 for SOD, P<0.01 for TRAP). The intragroup CVs of both methods were comparable for TRAP, while in the RLM determinations of SOD resulted in <50% of those obtained with the CKM. The ANCOVA comparison of the regression parameters across the clinical groups resulted significant for SOD (P<0.0001) and not significant for TRAP. Both methods agree in describing the features of the clinical groups, but the degree of agreement at the individual concentration was poor and they could not be readily intercalibrated. Normal and pathological values should be obtained independently for the CKM to insure their applicability to large populations.

Reproductive and brood cycles of Artemia persimilis Piccinelli & Prosdocimi from Colorada Chica Lake (Province of La Pampa, República Argentina), under laboratory conditions

The brood cycle in anostracans results from the overlapping of two successive reproductive cycles in the genital tract of females. While a clutch of oocytes begins to mature at the ovaries (ovarian period), the nauplii, cysts or unfertilised products of a previous clutch are developing in the ovisac or being released to the medium (oviduct-ovisac period). Models are proposed for the sequence of stages and their duration in a complete brood cycle under two treatments, i.e., females with males (1:1 ratio), and isolated virginal females of Artemia persimilis in laboratory conditions. The whole brood cycle in both treatments took 6 days, however, they differed in the duration of some stages. The differences are discussed and observations on amplexus are added.

Stroke vs. chronic progressive cerebrovascular disease: A magnetic resonance imaging study of symptomatic outpatients

Stroke is the main manifestation of cerebrovascular disease (CVD). Few studies report the insidious and progressive development of CVD. The aim of this study was the characterization of a CVD form without stroke in association with vascular subtypes and risk factors (VRF). From 105 CVD patients, 65 had stroke (62%), 13 of them had more than one stroke (20%), and 40 patients had a chronic progressive form (CPF) (38%). Mean evolution times up to maximum neurological deficiency were 1.57+/-0.94 and 344.25+/-210.96 days, respectively. Group results significantly associated with VRFs: hypertension (p=0.0046), hyperlipemia (p=0.0046) and atrial fibrillation (p=0.0173); with clinical manifestations: aphasia (p=0.0018), pyramidal syndrome (p=0.0000001) and small vessel disease (SVD) (p=0.0000001); and with MRI: bilateral infarctions (p=0.00009) and incomplete white matter lesions (IWMLs) (p=0.0061). Within the CPF group, dysarthria and complete infarctions were associated (p=0.00036). Most neurological disorders associated with CVD are related to CPF. The significant correlations of SVD, bilateral infarcts, IWMLs, dysarthria, several VRFs and the strong difference in evolution time up to maximum neurological deficiency values characterize CPF as a separate entity within CVD.

Estrés oxidativo en la enfermedad neurológica. ¿Es causa, consecuencia o induce una forma crónica progresiva?

Habiendo leído con mucho interés el editorial publicado en octubre del 2014, titulado «El estrés oxidativo en las enfermedades neurológicas: ¿causa o consecuencia?» y contestes con los conceptos expuestos por los autores1, resulta pertinente sumar algunos hechos y consideraciones publicados en la literatura científica durante los últimos 25 años. El estrés oxidativo sistémico (EOS) constituye básicamente un desbalance entre las especies reactivas del oxígeno (ERO) y del nitrógeno (especies oxidantes) y la capacidad de neutralizar su acción deletérea a través de los antioxidantes endógenos del organismo2 y exógenos (dieta y fármacos). Las distintas áreas neuronales que resultan afectadas en el encéfalo presentan variaciones en su morfología y metabolismo; probablemente, la individualidad de cada grupo de neuronas establezca la propia fortaleza o debilidad frente al estrés oxidativo. Los incrementos del estado de EOS —–que resulta cuantificable en muestras sanguíneas—– se observan en las enfermedades de Alzheimer (EA) y Parkinson (EP), esclerosis lateral amiotrófica, encefalopatía vascular crónica de la pequeña arteria (EV), epilepsias y ataxia de Friedreich, entre otras3-8. Asimismo, enfermedades de la clínica médica, tales como diabetes mellitus (DM), cáncer, aterosclerosis e inflamaciones crónicas del hígado, riñón y pulmón, se hallan asociadas a un estado de EOS. A partir de la década de los 90 se publicó que la relación ERO/antioxidantes se halla asociada con las EA, EP y EV; adicionalmente, se com-