Alzheimer disease and cognitive impairment associated with diabetes mellitus type 2: associations and a hypothesis.

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 ß-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.

Effect of partial sodium replacement on physicochemical parameters of smoked sea bass during storage.

The objective of this work was to study the effect of partial sodium replacement by potassium and packaging conditions on the physicochemical properties of smoked sea bass during cold storage. Sea bass fillets were salted with 100% NaCl (Na samples) or with 50% NaCl-50% KCl (Na:K samples), smoked, packaged under three different conditions (air, vacuum and modified atmosphere) and stored at 4 °C for 42 days. Physicochemical parameters, color and texture were periodically determined in the raw material and in smoked samples during cold storage. The smoking process led to a reduction in moisture, pH and a(w) values, and an increase in water holding capacity, ash and mineral contents. Smoked fish exhibited significant differences in color and texture as compared to fresh fish. The type of packaging had an effect on the pH, water holding capacity and texture. Samples in air exhibited the highest pH values and water holding capacity in these samples gradually decreased during storage. Textural parameters decreased during storage in samples packaged in vacuum and modified atmosphere. The pH of Na samples was initially higher than in Na:K samples, and this difference remained over the rest of the study. The type of salt did not affect the texture or other physicochemical parameters.

Recommendations for use of antigenic tests in the diagnosis of acute SARS-CoV-2 infection in the second pandemic wave: attitude in different clinical settings.

The high transmissibility of SARS-CoV-2 before and shortly after the onset of symptoms suggests that only diagnosing and isolating symptomatic patients may not be sufficient to interrupt the spread of infection; therefore, public health measures such as personal distancing are also necessary. Additionally, it will be important to detect the newly infected individuals who remain asymptomatic, which may account for 50% or more of the cases. Molecular techniques are the "gold standard" for the diagnosis of SARS-CoV-2 infection. However, the massive use of these techniques has generated some problems. On the one hand, the scarcity of resources (analyzers, fungibles and reagents), and on the other the delay in the notification of results. These two facts translate into a lag in the application of isolation measures among cases and contacts, which favors the spread of the infection. Antigen detection tests are also direct diagnostic methods, with the advantage of obtaining the result in a few minutes and at the very "pointof-care". Furthermore, the simplicity and low cost of these tests allow them to be repeated on successive days in certain clinical settings. The sensitivity of antigen tests is generally lower than that of nucleic acid tests, although their specificity is comparable. Antigenic tests have been shown to be more valid in the days around the onset of symptoms, when the viral load in the nasopharynx is higher. Having a rapid and real-time viral detection assay such as the antigen test has been shown to be more useful to control the spread of the infection than more sensitive tests, but with greater cost and response time, such as in case of molecular tests. The main health institutions such as the WHO, the CDC and the Ministry of Health of the Government of Spain propose the use of antigenic tests in a wide variety of strategies to respond to the pandemic. This document aims to support physicians involved in the care of patients with suspected SC2 infection, in the context of a growing incidence in Spain since September 2020, which already represents the second pandemic wave of COVID-19.

Microbial and sensory changes during refrigerated storage of desalted cod (Gadus morhua) preserved by combined methods.

Water blanching and the use of additives (potassium sorbate and citric acid) combined with different types of packaging (air, vacuum "VP" and modified atmosphere packaging "MAP": 60% CO(2), 30% N(2) and 10% O(2)), were studied as new methods of preservation of chilled desalted cod. Microbial counts and total volatile basic nitrogen (TVB-N) analyses were carried out during a period of 42 days on all samples stored at 4 degrees C. No Aeromonas or sulphite-reducing Clostridium were isolated from any of the analysed samples. The lowest microbial counts of mesophilic, psychrotrophic, Pseudomonas, moulds and yeasts, were found in samples with additives in all kinds of packaging. These samples in VP or MAP maintained an excellent microbial quality throughout the 42 days of storage, with mesophilic and psychrotrophic counts always below 4 log CFU/g. Counts of the four microorganisms above-mentioned in blanched samples packaged with air, exceeded 5 log CFU/g on days 21-28, so it became necessary to use VP or MAP to maintain these microorganisms at an acceptable level for the entire storage period. TVB-N contents were low in samples with additives, regardless of the kind of packaging, as well as in blanched samples packaged in VP and MAP, never reaching 25 mg/100 g. Since there were no significant differences either in microbial growth or in TVB-N between samples in VP and MAP, a sensory analysis was performed only in desalted cod submitted to the two treatments (blanching and additives) combined with VP, both in raw and cooked samples. The results of this analysis showed that the addition of potassium sorbate and citric acid did not alter the typical organoleptic features of desalted cod. The sensory characteristics of both blanched samples and those with additives in VP showed no change during the period of the study.

Peripheral markers and diagnostic criteria in Alzheimer's disease: critical evaluations.

This review analyzes recent developments in diagnostic criteria and peripheral markers used clinically in the definitive diagnosis of Alzheimer's disease (AD), comparing past and current views, together with a discussion of their shortcoming and difficulties of implementation. Consideration is given to studies on the presence of amyloid substances outside the central nervous system: in cerebrospinal fluid, in plasma, in primary cultures, and in continuous cultures of cell lines of neuronal and glial origin. We discuss alterations of cholinesterases and noradrenaline in red blood cells (RBC) in AD and, with relation to the infectious theory, the presence of spirochaetes in patients. The activities of the enzymes leading to the formation of amyloid substances and those reflecting more general alterations of metabolic processes are considered, both in respect to their role in the pathogenesis of the neurodegenerative disorders of AD and of their potential use as markers. Enzymatic changes have been studied comparing AD patients with non AD controls as well as with AD relatives: proteases and their inhibitors; plasminogen activators; transketolases; increases in the activity of Cu-Zn superoxide dismutase in AD patients' RBC, serum, fibroblasts and cortical neurons, pointing to alterations in oxidative processes; and apolipoprotein E epsilon 4 allele, linked to late-onset AD and familial cases. This review presents reasons why the involvement of peripheral markers in AD should advance from hypothesis to accepted fact.

Early lymphocyte activation in elderly humans: impaired T and T-dependent B cell responses.

Immunosenescence is characterized by an increase in autoantibody production. Because both T and B cell stimulation are key events for producing antibodies, we investigated early T and B cell activation by means of CD23 and CD40L (two very early activation antigens). PBMC from elderly humans (EH) were studied following culture with either medium, anti-CD3mAb, rIL-4, or PMA + ionomycin. CD23 expression on elderly B cells after anti-CD3 challenge of PBMC, a reflect of T-dependent B cell activation, was clearly defective. Conversely, CD23 expression on EH B cells following activation with soluble factors as rIL-4 was preserved. CD40L expression was also impaired in EH T cells following anti-CD3 challenge. However, activation by means of PMA and/or ionomycin was preserved both in T cells (CD40L expression) and in B cells (CD23 expression). These results indicate that a defective T-dependent B cell activation related to defective T cell activation located between surface membrane and PKC/ionomycin function is an intrinsic characteristic of immunosenescence. We have not found intrinsic B-cell defects, and we conclude that the characteristically impaired early B cell activation in EH is mostly due to T cell defects.

Copper-zinc superoxide dismutase activity in red blood cells and serum in demented patients and in aging.

The activity of the enzyme copper-zinc superoxide dismutase (Cu-Zn SOD) has been investigated in serum and red blood cells (RBC) homogenate obtained from demented patients with associated vascular lesions (VD), demented patients with probable Alzheimer's disease (DAT) and healthy controls (CG) of the same age. The increase in SOD activity was statistically significant (P < 0.01) in RBCs homogenate of DAT and VD patients, when compared to controls, but no differences appear between the two diseases groups. Additionally, a statistically significant increase in SOD activity (P < 0.01) in DAT patients above 70 years as compared to those 50-70 years old, and a relation between SOD and age were found. No changes in SOD activity with age in healthy controls nor in vascular dementia group were detected. A statistically significant increase in Circulating SOD activity (P < 0.01) was observed in vascular patients compared to controls. The observed increase in DAT Circulating SOD activity (against CG) was not significant. The increased levels of Cu-Zn SOD, probably represent a general alteration of the oxidative processes characteristic of these dementias and suggest that the enzyme might be used as a marker.

Copper-zinc superoxide dismutase activity in red blood cells in probable Alzheimer's patients and their first-degree relatives.

The activity of the enzyme copper-zinc superoxide dismutase (Cu-Zn SOD) has been investigated in red blood cell (RBC) homogenate obtained from demented patients with probable Alzheimer's disease (DAT), from their first-degree relatives (sisters/brothers and sons/daughters), and from healthy control families of the same age. A statistically significant increase in SOD activity (P < 0.01) was found in RBC's homogenate between families of DAT patients (not including the demented individual) and control families. Variability in SOD activity due to differences between families was not significant for DAT relatives; a significant variance component (P < 0.05) was found between control families. Additionally, a statistically significant increase in SOD activity (P < 0.001) with age in DAT patients up to 70 years and a significant decrease above this age were found, confirming a previously found relation. No changes in SOD activity with age were detected in healthy controls nor in DAT relatives. The increased levels of Cu-Zn SOD, probably represent a general alteration of the oxidative processes characteristic of this dementia and support the proposal that the enzyme could be used as an early diagnostic peripheral marker of the Alzheimer's disease (AD), and to determine to which subgroup the patient belongs, as well as a risk factor in non-demented first-degree relatives.

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 Alzheimer's (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.

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 Alzheimer's, Parkinson's, and vascular dementia patients and controls. The lack of fit and the run's 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.

Risk assessment and critical control points from the production perspective.

The implementation of a risk analysis program as risk assessment and critical control points (RACCP) is most necessary in order to accomplish the foodborne industries current objective of total quality. The novelty of this technique, when compared to actual hazard analysis and critical control points (HACCP) and its extension to incorporate elements of quantitative risk analysis (QRA), is that RACCP considers the risk of the consequences produced by the production process performance deviations, both inside and outside the company, and also identifies their causative factors. On the other hand, the techniques to be taken in order to prevent or mitigate the consequences of such deviations must be consistent with the former data, but the need for a cost-benefit assessment must not be ignored so that the chosen technique be most profitable for the company. An example developed in a mineral water bottling plant showed that RACCP application is feasible and useful. During this example case, RACCP demonstrated it could obtain a profitable production process that keeps quality and safety of the final product at its maximum, while providing protection to both company and consumer.

[Cerebrovascular disease and gait disorders: qualitative and quantitative analysis]. / Enfermedad cerebrovascular y alteraciones de la marcha: análisis cualitativo y cuantitativo.

INTRODUCTION AND OBJECTIVE: Pyramidal gait impairment (GI) is a classical trait of cerebrovascular disease (CVD). To developed a method to quantify prospectively and transversely GI and disequilibrium, to be applied in the screening of pyramidal and non-pyramidal syndromes associated to different ethiological subtypes of CVD; using an Index of Gait and Equilibrium (IGE). PATIENTS AND METHODS: In constructing IGE, we used 14 equally weighted semiological variables: 6 measure balance, 6 gait, 1 sensitive abnormalities and 1 falls. Two neurologists separately examined each subject in the same day and repeating the evaluation after a week. Data analyses included Kruskal Wallis, chi 2, Spearman correlations and Principal Components. RESULTS: IGE was used in 90 subjects, 43 males, with a mean age of 70.6 years. 3 groups of people were formed: 1. CVD (A, 21 with silent vascular lesions diagnosed by imaging; B, 17 with vascular dementia; C, 21 with stroke); 2. 13 subjects with cautious gait, not associated to any disease; and 3. 18 normal control subjects (age 60-80 years). GI in the non-pyramidal syndrome were significantly related with small vessels disease (chi 2 = 16.37, dof = 1, p < 0.001). CONCLUSIONS: GI in CVD, pyramidal and non-pyramidal syndromes were equally frequent. Increased values of IGE caused by cautious gait in youngest non-stroke patients suggested high probability of silent CVD and significant association with small vessels disease. This preliminary assessment of IGE showed a reproducible and reliable tool for objectification and quantification of gait disorders.

[Epidemiology of hip fractures in the elderly in Spain]. / Epidemiología de la fractura de cadera en ancianos en España.

BACKGROUND: Ninety percent of hip fractures (HF) occur in people older than 64 years. We describe the epidemiological data (age, sex, date of admission and discharge and mortality) of elderly with hip fracture in the different regions of Spain. METHOD: Data obtained from the Minimum Data Set of the Ministry of Health were used to analyse hip fracture incidence (Identified by codes 820.0 through 820.9 of the International Classification of Diseases) from 1996 through 1999. Demographic data of Spanish population were obtained from the National Institute of Statistics. HF rates were calculated using crude and age-and-sex adjusted density of incidence. Factors associated with in-hospital mortality were assessed by multivariate analyses. RESULTS: 89% (130.414) of 146.383 HF cases studied were in elderly patients with a mean age of 82 years old, being 78% females. The results showed a great variability through the different regions. Length of hospital stay was 16 days, and in-hospital mortality was 5%. Global HF rate was 517 cases per 100.000 elderly per year (270 cases/100.000 elderly males and 695/100.000 elderly females). In-hospital mortality was higher in males than females (8.1% vs 4.2%, respectively), increases progressively with age and it is higher during winter months. Factors associated with mortality were old age, male gender, fractured in winter, and living in Regions others than Mediterranean and Canary Islands. CONCLUSIONS: Hip fracture is a condition that occurs more commonly in elderly people. It is more frequent in females and shows a great variation in incidence, mortality and length of hospital stay through different Spanish regions.

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

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 x 10(-3); Glucose p < 10(-12); Glycohemoglobin p = 9.2x10(-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, alpha = 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.

[Previous history of gastrectomy in the aged: a malnutrition with malignant aspect]. / Antecedentes de gastrectomía en el anciano: una desnutrición de aspecto maligno.

Between 1979 and 1986 a prospective study was performed on 15 gastrectomized (Billroth II) patients, who were above 65 years old, with evidence of clinical malnutrition as defined by anthropometric criteria. Gastrectomy had been performed between 2 and 55 years before the study (29 +/- 12.87 years). In twelve patients weight loss was observed ranging from 5.85 and 11.91 kg in a mean period of 12.7 months immediately prior to admission. In 8 cases the initial diagnosis was of malignancy, in 2 cases of severe anemia, and in 1 case of severe malnutrition. Intestinal malabsorption (IMB) was observed in 5 cases and intestinal bacterial overgrowth (IBO) in 2 cases, and both diagnosis in 4 cases using stool fat test and D-xylose test for the diagnosis of IMB and urine determination of Urican for the diagnosis of IBO. In two patients the test were normal and they could not be performed in two other. In 3 patients malignancy could not be observed however one of them presented IMB and the other IMB and IBO. We conclude that gastrectomy when performed in earlier ages can cause malnutrition at an older age, provoking a sudden malnutrition suggestive of malignancy. Most of these patients present IMB and/or IBO. Since IBO can cause irreversible mucosal damage, it is discussed whether this could be the cause of this clinical picture.

Early T-cell activation in elderly humans.

This study characterizes the early steps of T lymphocyte activation in elderly subjects. The expression of CD69, the earliest inducible antigen which appears with T lymphocyte activation, was assessed in T cells cultured with medium, anti-CD3 or PMA. The proliferative responses of T cells stimulated through CD69 and CD3 pathways were also studied. Donors included 31 healthy elderly [age mean (SD) 80(8) years] and 33 healthy young [age 30(5) years] subjects. In elderly people, the expression of CD69 was lower in T cells cultured with medium [3.4% (1.65-5.9; 25-75 percentiles) vs. 10% (6-18), p < 0.0003] and anti-CD3 activated [28.1% (16.5-53.8) vs. 79.5% (73-89), p < 0.0002] T cells. With PMA at 10 ng/ml, CD69 expression was higher in both groups of T cells, though still lower in the aged [84.5% (70.9-94.9) vs. 99% (65.7-100), p = 0.051]. CD69 T cells expression was equal in both groups with 2 ng/ml of PMA, but the co-stimulatory responses to CD69 under these conditions and in the presence of anti-CD3 were lower in the aged (16914 vs. 28904 cpm, p < 0.02) and (6944 vs. 14370 cpm, p < 0.02) respectively. Aged T cells failed to express CD25 at the same levels of young T cells when stimulated with CD69. These results suggests an age-associated defect in the very early steps of T lymphocyte activation that might influence later stages of lymphocyte function. An alteration in the transmission of the activation signal from the cell surface to protein kinase C may play a primary role in this defect.

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

Antioxidant profiles in Parkinson's disease (PD; n = 15), dementias of Alzheimer's 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 multi-variate 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.

Functional integrity of the CD28 co-stimulatory pathway in T lymphocytes from elderly subjects.

INTRODUCTION: the antigen CD28, expressed in most T cells, has co-stimulatory properties and plays a pivotal role in clonal T cell anergy mechanisms. METHODS: we have compared proliferative T cell responses after anti-CD3 or in phorbol myristate acetate activation with concomitant CD28 signal in peripheral blood mononuclear cells from healthy donors aged over 65 [elderly donors; ED] and young healthy donors (YD); mean age 30+/-2.7 years). RESULTS: no proliferative responses were observed in ED and YD with anti-CD28 monoclonal antibody alone. These responses both were defective in ED, particularly after anti-CD3 monoclonal antibody stimulus (7604 compared with 12,438 c.p.m. in YD, P=0.001) and were corrected when anti-CD28 monoclonal antibody was added to the culture (17,216 vs 18,536, not significant). Functional integrity of the CD28 co-stimulatory pathway was demonstrated by analysis of CD25 expression, interleukin-2 secretion and interleukin-2 gene expression on T cells from ED and YD. Age-associated phenotypic T cell changes were not crucial for an adequate CD28 response. CONCLUSION: these experiments demonstrate the integrity of the CD28 pathway in elderly people, and suggest that ageing does not affect different T cell activation pathways equally.