Associations between self-reported sleep quality and cerebrospinal fluid biomarkers in mild cognitive impairment and Alzheimer's disease.

Sleep disorders are very common in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Several parameters of polysomnography seem to correlate with cognitive scores and amyloid biomarkers in the different stages of AD. However, there is limited evidence for the relationship between self-reported sleep impairment and disease biomarkers. In this study, we assessed the relationship between self-reported sleep complaints, with the Pittsburgh Sleep Quality Index, and both cognitive function and cerebrospinal fluid biomarkers in 70 patients with MCI and 78 patients with AD. Sleep duration and daytime dysfunction were higher in AD. Daytime dysfunction had a negative correlation with cognitive scores (Mini-Mental-State Examination and Montreal Cognitive Assessment) and with amyloid-beta1-42 protein, and a positive correlation with total tau protein. However, daytime dysfunction was an independent predictor only of t-tau values (F=57.162; 95% CI: [18.118; 96.207], P=0.004). These findings support a relationship between daytime dysfunction, cognitive scores and neurodegeneration, further expanding recent findings that it may signal a risk of dementia.

[Adjuvant treatments to invasive mechanical ventilation in the management of acute respiratory distress syndrome secondary to COVID-19]. / Tratamientos coadyuvantes a la ventilación mecánica invasiva en el manejo del síndrome de distrés respiratorio agudo secundario a covid-19.

Introduction: This bibliographic review is carried out in order to obtain answers about aspects related to techniques and treatments, as well as care associated with the critically ill patient diagnosed with COVID-19. Objective: To analyze the available scientific evidence on the effectiveness of the use of invasive mechanical ventilation together with other adjuvant techniques, in reducing the mortality rate in patients with acute respiratory distress syndrome and clinical trial of COVID-19 treated in intensive care units. Methodology: A systematized bibliographic review was carried out in the PubMed, CUIDEN, LILACS, Medline, CINAHL and Google Scholar databases, using MeSH terms (adult respiratory distress syndrome, mechanical ventilation, prone position, nitric oxide, extracorporeal membrane oxygenation, nursing care) and the corresponding Boolean operators. The selected studies underwent a critical reading carried out between December 6, 2020 and March 27, 2021 using the Critical Appraisal Skills Program tool in Spanish and a cross-sectional epidemiological studies evaluation instrument. Results: A total of 85 articles were selected. After performing the critical reading, a total of 7 articles were included in the review, 6 being descriptive studies and one a cohort study. After analyzing these studies, it appears that the technique that has obtained the best results is extracorporeal membrane oxygenation, with the care provided by qualified and trained nursing staff being very important. Conclusion: Mortality from COVID-19 increases in patients treated with invasive mechanical ventilation compared to patients treated with extracorporeal membrane oxygenation. Nursing care and specialization can have an impact on improving patient outcomes.

Efficacy of the laser at low intensity on primary burning oral syndrome: a systematic review.

BACKGROUND: Primary burning mouth syndrome (BMS) is a chronic clinical condition of idiopathic mainly characterized by pain and a burning sensation in the oral cavity. The application of laser at low intensity therapy is a treatment option. This systematic review evaluated the efficacy of laser therapy in treating symptoms of burning mouth syndrome. MATERIAL AND METHODS: The study was formulated according to the PRISMA and Cochrane guidelines. Seven databases were used as primary sources of research. Only randomized controlled clinical trials were included. The efficacy of the therapy was estimated comparing the values of the visual and numerical scales of pain before and after laser treatment, through qualitative analysis. RESULTS: The search resulted in 348 records and only eight filled the eligibility criteria and were included. All studies evaluated pain and / or a burning sensation considering a time interval of two to ten weeks. The total sample consisted of 314 patients submitted to treatment: 123 from the control group, who participated with laser off or with the tip blocked, and 191 from the intervention group, treated with low-level laser therapy. The female gender stood out and the average age of the participants was 60.89 years. The main symptoms reported were pain and a burning sensation in the oral mucosa and tongue. The parameters adopted by the authors for laser treatment were diverse and the variables were not fully described in the published studies. Visual analog and numerical scales were used to assess symptoms and only three studies showed statistical significance. CONCLUSIONS: It is suggested that laser therapy may be an effective alternative in the treatment of BMS. New randomized clinical trials should consider well-established protocols to better understand the efficacy of laser therapy without confounding the effects.

Immunohistochemical expression of cyclooxygenase-2 (COX-2) in feline endometrial adenocarcinoma and in normal and hyperplastic endometria.

Cyclooxygenase-2 (COX-2) is overexpressed in several human and animal neoplasms, including the human endometrial carcinoma. It has been suggested as a prognostic marker and a potential therapeutic target. This study aimed to (i) clarify histological aspects of feline endometrial adenocarcinomas (FEA) of the papillary serous type and (ii) characterize COX-2 immunohistochemical expression in normal, hyperplastic and neoplastic endometrium in this species. Archived paraffin-embedded tissue samples of 33 FEA, eight cystic endometrial hyperplasias (CEHs) and 21 samples of normal, healthy endometrium in the follicular (FS; n = 10) and luteal (LS; n = 11) stages were evaluated. Histological evaluation of haematoxylin and eosin-stained sections of the FEA revealed a papillary proliferation of neoplastic cells of serous type, accompanied by clear and multinucleated cells. Other architectural arrangements mainly included solid and tubular growth. Randomly distributed areas of necrosis within the tumours were commonly observed. Invasion of the myometrium, of the serosa and of the vascular and/or lymphatic vessels was not constant features. The mean number of mitoses was higher in FEA compared to non-neoplastic endometrium. COX-2 scores were lower in FEA (p = 0.003) and CEH (p = 0.05) when compared to normal epithelium (NE). The loss of the membrane apical reinforcement in epithelial cells was observed in FEA samples, which was accompanied by the dislocation of COX-2 labelling into the cytoplasm and the perinuclear area; in contrast, in epithelial cells in the healthy and hyperplastic endometria, the immunoreaction showed the characteristic pattern of apical membrane reinforcement, suggestive of the membrane polarization. COX-2 epithelial scores were higher in the FS than in the LS. No differences were found in stromal COX-2 expression between normal, CEH and FEA groups, but it was higher in the LS than in the FS. In summary, loss of COX-2 compartmentalization in neoplastic epithelial cells might be one of the molecular events underlying endometrial carcinogenesis.

Benign episodic mydriasis. Experience in a specialist neuro-ophthalmology clinic of a tertiary hospital.

INTRODUCTION: Anisocorias are a relatively frequent reason for consultation in neuro-ophthalmology units. They remain a diagnostic challenge for specialists as they may be due to several etiological factors. In the absence of other accompanying symptoms, anisocorias are usually due to benign processes. Benign episodic mydriasis (BEM) is an isolated cause of intermittent pupil asymmetry, in which the pathophysiology is still not fully understood, and is predominant in young women with migraine. SUBJECTS, MATERIAL AND METHODS: We describe the epidemiological and clinical characteristics of patients with BEM, assessed in a neuro-ophthalmology unit in a tertiary hospital. RESULTS: A total of 7 patients were diagnosed with BEM, all of them females, with a mean age of 33 ± 10 yrs. The patients presented with pupil asymmetry (n = 5) and blurred vision (n = 2), and 6 of the 7 patients had unilateral involvement. The duration of impairment varied from a few minutes to 48 hrs. Four patients (57%) had a clinical history of migraine without aura. The episodes in these 4 patients were recurrent (75%), often lasted for a few minutes (75%), and had associated blurred vision (50%). The neuroimaging studies were normal. DISCUSSION: BEM appears predominantly in young women. It is frequently related to a previous history of migraine, and the specialist must consider if it is a concomitant symptom of common migraine, migraine with aura, or ophthalmoplegic migraine. Although BEM has unilateral predominance, there may be alternation of the affected eye or even bilateral impairment during the same episode, which makes us question the adequacy of the term to describe the process. Imaging tests are not recommended in the absence of other accompanying symptoms, or in short-term episodes.

Adjuvant treatments to invasive mechanical ventilation in the management of acute respiratory distress syndrome secondary to COVID-19.

INTRODUCTION: This bibliographic review is carried out in order to obtain answers about aspects related to techniques and treatments, as well as care associated with the critically ill patient diagnosed with Covid-19. OBJECTIVE: To analyze the available scientific evidence on the effectiveness of the use of invasive mechanical ventilation together with other adjuvant techniques, in reducing the mortality rate in patients with Acute Respiratory Distress Syndrome and clinical trial of Covid-19 treated in intensive care units. METHODOLOGY: A systematized bibliographic review was carried out in the Pubmed, Cuiden, Lilacs, Medline, Cinahl and Google Scholar databases, using MeSH terms (Adult Respiratory Distress Syndrome, Mechanical Ventilation, Prone Position, Nitric Oxide, Extracorporeal Membrane Oxygenation, Nursing Care) and the corresponding Boolean operators. The selected studies underwent a critical reading carried out between December 6, 2020 and March 27, 2021 using the Critical Appraisal Skills Program tool in Spanish and a cross-sectional epidemiological studies evaluation instrument. RESULTS: A total of 85 articles were selected. After performing the critical reading, a total of 7 articles were included in the review, 6 being descriptive studies and 1 cohort study. After analyzing these studies, it appears that the technique that has obtained the best results is ECMO, with the care provided by qualified and trained nursing staff being very important. CONCLUSION: Mortality from Covid-19 increases in patients treated with invasive mechanical ventilation compared to patients treated with extracorporeal membrane oxygenation. Nursing care and specialization can have an impact on improving patient outcomes.

Global pharmacogenomics: Impact of population diversity on the distribution of polymorphisms in the CYP2C cluster among Brazilians.

The impact of biogeographical ancestry, self-reported 'race/color' and geographical origin on the frequency distribution of 10 CYP2C functional polymorphisms (CYP2C8*2, *3, *4, CYP2C9*2, *3, *5, *11, CYP2C19*2, *3 and *17) and their haplotypes was assessed in a representative cohort of the Brazilian population (n=1034). TaqMan assays were used for allele discrimination at each CYP2C locus investigated. Individual proportions of European, African and Amerindian biogeographical ancestry were estimated using a panel of insertion-deletion polymorphisms. Multinomial log-linear models were applied to infer the statistical association between the CYP2C alleles and haplotypes (response variables), and biogeographical ancestry, self-reported Color and geographical origin (explanatory variables). The results showed that CYP2C19*3, CYP2C9*5 and CYP2C9*11 were rare alleles (<1%), the frequency of other variants ranged from 3.4% (CYP2C8*4) to 17.3% (CYP2C19*17). Two distinct haplotype blocks were identified: block 1 consists of three single nucleotide polymorphisms (SNPs) (CYP2C19*17, CYP2C19*2 and CYP2C9*2) and block 2 of six SNPs (CYP2C9*11, CYP2C9*3, CYP2C9*5, CYP2C8*2, CYP2C8*4 and CYP2C8*3). Diplotype analysis generated 41 haplotypes, of which eight had frequencies greater than 1% and together accounted for 96.4% of the overall genetic diversity. The distribution of CYP2C8 and CYP2C9 (but not CYP2C19) alleles, and of CYP2C haplotypes was significantly associated with self-reported Color and with the individual proportions of European and African genetic ancestry, irrespective of Color self-identification. The individual odds of having alleles CYP2C8*2, CYP2C8*3, CYP2C9*2 and CYP2C9*3, and haplotypes including these alleles, varied continuously as the proportion of European ancestry increased. Collectively, these data strongly suggest that the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of pharmacogenomic studies of the CYP2C cluster in order to avoid spurious conclusions based on improper matching of study cohorts. This conclusion extends to other polymorphic pharmacogenes among Brazilians, and most likely to other admixed populations of the Americas.

The temporal stability of premorbid intelligence: A non-clinical 10-year follow-up study using the Irregular Word Reading Test (TeLPI).

INTRODUCTION: The Cognitive Reserve (CR) describes the brain's ability to actively cope with neurological damage, enabling the maintenance of premorbid cognitive functioning through compensatory processes. The most common way to estimate CR is through formal education, the intelligence quotient (IQ) and participation in cognitive stimulating activities. In the absence of IQ data, the Irregular Word Reading Test (TeLPI) allows you to estimate the premorbid intelligence. OBJECTIVE: The comparison of the TeLPI results between two times of assessment (baseline and re-assessment) with an interval time (IT) of 9 years. To analyze of the stability of their results as a valid dimension for the CR estimation. RESULTS: The TeLPI presented temporal stability of its results between the two evaluation times (IT = 9.07 ± 1.02). The sample, composed by 63 cognitively healthy participants, showed no differences for the estimated Full Scale IQ (t(62) = 0.49, p = .63), for the Estimated Verbal IQ (t(62) = 0.71, p = .48) and for the estimated Performance IQ (t(62) = 0.64, p = .52). Likewise, no differences were found in the number of TeLPI errors at the two assessment times (t(62) = -0.61, p = .54). CONCLUSIONS: Considering that CR is characterized as being relatively stable, the TeLPI should be included in its assessment, as an indicator with proved stability over a long period of time, on the physiological aging spectrum.

Semi-quantification and grading of amyloid PET: A project of the European Alzheimer's Disease Consortium (EADC).

BACKGROUND: amyloid-PET reading has been classically implemented as a binary assessment, although the clinical experience has shown that the number of borderline cases is non negligible not only in epidemiological studies of asymptomatic subjects but also in naturalistic groups of symptomatic patients attending memory clinics. In this work we develop a model to compare and integrate visual reading with two independent semi-quantification methods in order to obtain a tracer-independent multi-parametric evaluation. METHODS: We retrospectively enrolled three cohorts of cognitively impaired patients submitted to 18F-florbetaben (53 subjects), 18F-flutemetamol (62 subjects), 18F-florbetapir (60 subjects) PET/CT respectively, in 6 European centres belonging to the EADC. The 175 scans were visually classified as positive/negative following approved criteria and further classified with a 5-step grading as negative, mild negative, borderline, mild positive, positive by 5 independent readers, blind to clinical data. Scan quality was also visually assessed and recorded. Semi-quantification was based on two quantifiers: the standardized uptake value (SUVr) and the ELBA method. We used a sigmoid model to relate the grading with the quantifiers. We measured the readers accord and inconsistencies in the visual assessment as well as the relationship between discrepancies on the grading and semi-quantifications. CONCLUSION: It is possible to construct a map between different tracers and different quantification methods without resorting to ad-hoc acquired cases. We used a 5-level visual scale which, together with a mathematical model, delivered cut-offs and transition regions on tracers that are (largely) independent from the population. All fluorinated tracers appeared to have the same contrast and discrimination ability with respect to the negative-to-positive grading. We validated the integration of both visual reading and different quantifiers in a more robust framework thus bridging the gap between a binary and a user-independent continuous scale.

Variant Creutzfeldt-Jakob [corrected] disease: the second case in Portugal and in the same geographical region.

We present the second variant Creutzfeldt-Jacob patient in the same district of northwest Portugal as was previously reported. A 14-year-old previously healthy girl had unexplained pain in the left leg, as well as psychiatric disturbances. This was shortly followed by progressive cognitive impairment, ataxia and generalised choreoatethosis. Neuropsychological assessment revealed severe frontal and medial temporal dysfunction, the posterior cortices being spared. An electroencephalogram was normal. CSF 14.3.3 protein was slightly positive. Magnetic resonance imaging showed the "hockey stick sign" and hyperintensities in the periaquedutal grey matter and in the right parietal cortex, the last with restriction to water molecule movement. SPECT revealed perfusion defects in the left frontotemporal and right parietal regions. PRNP gene sequencing showed no mutations, the patient being homozygous to methionine in codon 129. Five months after onset, immunocytochemical and immunoblotting analysis confirmed deposition of prion protein and a PrP4t electrophoretic pattern. The patient never travelled outside Portugal or received blood transfusions. She had surgical herniorrhaphy in 1998 (when catgut was used) and 2003. This is the second case in Portugal in a 2-year period and 20 km apart from each other, with no known common exposure apart from ingestion of cow meat. We discuss these case peculiarities and underline its epidemiological significance.

Genetic basis of Alzheimer's dementia: role of mtDNA mutations.

Alzheimer's disease (AD) is the most common neurodegenerative disorder associated to dementia in late adulthood. Amyloid precursor protein, presenilin 1 and presenilin 2 genes have been identified as causative genes for familial AD, whereas apolipoprotein E epsilon4 allele has been associated to the risk for late onset AD. However, mutations on these genes do not explain the majority of cases. Mitochondrial respiratory chain (MRC) impairment has been detected in brain, muscle, fibroblasts and platelets of Alzheimer's patients, indicating a possible involvement of mitochondrial DNA (mtDNA) in the aetiology of the disease. Several reports have identified mtDNA mutations in Alzheimer's patients, suggesting the existence of related causal factors probably of mtDNA origin, thus pointing to the involvement of mtDNA in the risk contributing to dementia, but there is no consensual opinion in finding the cause for impairment. However, mtDNA mutations might modify age of onset, contributing to the neurodegenerative process, probably due to an impairment of MRC and/or translation mechanisms.

Sporadic Creutzfeldt-Jakob disease diagnostic accuracy is improved by a new CSF ELISA 14-3-3γ assay.

Protein 14-3-3 is a reliable marker of rapid neuronal damage, specifically increased in cerebrospinal fluid (CSF) of sporadic Creutzfeldt-Jakob disease (sCJD) patients. Its detection is usually performed by Western Blot (WB), prone to methodological issues. Our aim was to evaluate the diagnostic performance of a recently developed quantitative enzyme-linked immunosorbent (ELISA) assay for 14-3-3γ, in comparison with WB and other neurodegeneration markers. CSF samples from 145 patients with suspicion of prion disease, later classified as definite sCJD (n=72) or Non-prion diseases (Non-CJD; n=73) comprised our population. 14-3-3 protein was determined by WB and ELISA. Total Tau (t-Tau) and phosphorylated Tau (p-Tau) were also evaluated. Apolipoprotein E gene (ApoE) and prionic protein gene (PRNP) genotyping was assessed. ELISA 14-3-3γ levels were significantly increased in sCJD compared to Non-CJD patients (p<0.001), showing very good accuracy (AUC=0.982; sensitivity=97%; specificity=94%), and matching WB results in 81% of all cases. It strongly correlated with t-Tau and p-Tau (p<0.0001), showing slightly higher specificity (14-3-3 WB - 63%; Tau - 90%; p-Tau/t-Tau ratio - 88%). From WB inconclusive results (n=44), ELISA 14-3-3γ correctly classified 41 patients. Additionally, logistic regression analysis selected ELISA 14-3-3γ as the best single predictive marker for sCJD (overall accuracy=93%). ApoE and PRNP genotypes did not influence ELISA 14-3-3γ levels. Despite specificity for 14-3-3γ isoform, ELISA results not only match WB evaluation but also help discrimination of inconclusive results. Our results therefore reinforce this assay as a single screening test, allowing higher sample throughput and unequivocal results.

Pseudohypoparathyroidism type I-b with neurological involvement is associated with a homozygous PTH1R mutation.

Pseudohypoparathyroidism type 1b (PHP1b) is characterized by hypocalcemia, hyperphosphatemia, increased levels of circulating parathyroid hormone (PTH), and no skeletal or developmental abnormalities. The goal of this study was to perform a full characterization of a familial case of PHP1b with neurological involvement and to identify the genetic cause of disease. The initial laboratory profile of the proband showed severe hypocalcemia, hyperphosphatemia and normal levels of PTH, which was considered to be compatible with primary hypoparathyroidism. With disease progression the patient developed cognitive disturbance, PTH levels were found to be slightly elevated and a picture of PTH resistance syndrome seemed more probable. The diagnosis of PHP1b was established after the study of family members and blunted urinary cAMP results were obtained in a PTH stimulation test. Integration of whole genome genotyping and exome sequencing data supported this diagnosis by revealing a novel homozygous missense mutation in PTH1R (p.Arg186His) completely segregating with the disease. Here, we demonstrate segregation of a novel mutation in PTH1R with a phenotype of PHP1b presenting with neurological symptoms, but no bone defects. This case represents the extreme end of the spectrum of cognitive impairment in PTH dysfunction and defines a possible novel form of PHP1b resulting from the impaired interaction between PTH and PTH1R.

CSF Tau proteins reduce misdiagnosis of sporadic Creutzfeldt-Jakob disease suspected cases with inconclusive 14-3-3 result.

Cerebrospinal fluid (CSF) 14-3-3 protein supports sporadic Creutzfeldt-Jakob (sCJD) diagnosis, but often leads to weak-positive results and lacks standardization. In this study, we explored the added diagnostic value of Total Tau (t-Tau) and phosphorylated Tau (p-Tau) in sCJD diagnosis, particularly in the cases with inconclusive 14-3-3 result. 95 definite sCJD and 287 patients without prion disease (non-CJD) were included in this study. CSF samples were collected in routine clinical diagnosis and analysed for 14-3-3 detection by Western blot (WB). CSF t-Tau and p-Tau were quantified by commercial ELISA kits and PRNP and APOE genotyping assessed by PCR-RFLP. In a regression analysis of the whole cohort, 14-3-3 protein revealed an overall accuracy of 82 % (sensitivity = 96.7 %; specificity = 75.6 %) for sCJD. Regarding 14-3-3 clear positive results, we observed no added value either of t-Tau alone or p-Tau/t-Tau ratio in the model. On the other hand, considering 14-3-3 weak-positive cases, t-Tau protein increased the overall accuracy of 14-3-3 alone from 91 to 94 % and specificity from 74 to 93 % (p < 0.05), with no sensitivity improvement. However, inclusion of p-Tau/t-Tau ratio did not significantly improve the first model (p = 0.0595). Globally, t-Tau protein allowed a further discrimination of 65 % within 14-3-3 inconclusive results. Furthermore, PRNP MV genotype showed a trend to decrease 14-3-3 sensitivity (p = 0.051), but such effect was not seen on t-Tau protein. In light of these results, we suggest that t-Tau protein assay is of significant importance as a second marker in identifying 14-3-3 false-positive results among sCJD probable cases.

Effects of apolipoprotein E genotype on blood lipid composition and membrane platelet fluidity in Alzheimer's disease.

The blood lipid composition (plasma, platelets and leukocytes), platelet membrane fluidity, apolipoproteins A and B in the plasma of AD patients and control subjects with distinct Apo E genotypes were investigated. No significant differences were found between the Apo E genotype and the cholesterol, phospholipids, triglycerides and Apo B levels in the plasma; cholesterol and phospholipids levels in platelet and leukocyte membranes; and platelet membrane fluidity of AD and control groups. However, the phospholipid levels in the leukocyte membranes of the control subgroup with the genotypes epsilon3/epsilon3 and epsilon3/epsilon4 and the AD subgroups with the genotypes epsilon2/epsilon3 and epsilon3/epsilon3, epsilon3/epsilon4 and epsilon4/epsilon4 were significantly lower than those observed in the control subgroup with the genotype epsilon2/epsilon3. Moreover, the cholesterol and phospholipid levels in the platelet membranes of the AD subgroup with the epsilon2 allele were significantly higher than those in the AD subgroup without the epsilon2 allele and the control subgroups with and without the epsilon2 allele. A strong correlation was found between cholesterol and phospholipids levels in the platelet membranes of the AD and control subgroups without the epsilon2 allele, but the residual cholesterol level in the platelet membranes of the AD subgroup was twice that observed in the control subgroup. Furthermore, the Apo A levels in the plasma of the AD subgroup with the epsilon3 allele were significantly lower than those observed in the AD subgroup without the epsilon3 allele and the control subgroup with the epsilon3 allele. The results are discussed in terms of involvement of lipid metabolism in the etiopathogenesis of AD.

Twenty-four-hour intragastric acidity and clinical trial of bedtime enprostil 70 micrograms compared with ranitidine 300 mg in duodenal ulcer.

The effects of bedtime 70 micrograms and twice daily 35 micrograms doses of enprostil on 24-hour intragastric acidity were investigated in nine duodenal ulcer patients in remission. Median nocturnal acidity decreased significantly by 30% with 35 micrograms twice daily, and by 48% with 70 micrograms at bedtime. In a clinical trial using bedtime dosing, 102 duodenal ulcer patients randomly received either ranitidine 300 mg or enprostil 70 micrograms. More ulcers healed after 4 and 8 weeks treatment with ranitidine than with enprostil (76% ranitidine vs 52% enprostil, at 4 weeks p = 0.0065 and 94% vs 68%, respectively at 8 weeks, P = 0.0007). However, 6 months after cessation of treatment there was no material difference in overall outcome. Despite combining mucosal protection with acid inhibition enprostil treatment conferred no advantage over simple acid inhibition.

Apolipoprotein E genotype has no effect on the free intracellular Ca2+ concentration of platelets from Alzheimer's disease patients.

The free intracellular Ca2+ concentration [Ca2+]i of platelets was investigated in Alzheimer's disease (AD) patients and age-matched control subjects with distinct Apo E genotypes. No significant differences were found between the Apo E genotype and the [Ca2+]i levels of platelets (basal and alpha-thrombin stimulated) from AD patients and age-matched control subjects, suggesting that [Ca2+]i homeostasis of platelets from AD patients is independent of the Apo E genotype. The results are discussed in terms of involvement of Apo E and [Ca2+]i changes in the etiopathogenesis of AD.

Influence of apolipoprotein E genotype on blood redox status of Alzheimer's disease patients.

The blood redox status of probable Alzheimer's Disease (AD) patients and control subjects with distinct Apo E genotypes was investigated. It was assessed by measuring the levels of hydroperoxides (MDA) in plasma and erythrocytes, the levels of the antioxidant defense system (enzymatic and non-enzymatic) in plasma, erythrocytes, platelets and leukocytes, the activities of catechol-O-methyltransferase (COMT) in erythrocytes and monoamine oxidase-B (MAO-B) in platelets and also the activity of the mitochondrial respiratory chain in leukocytes. No significant differences were found between the Apo E genotype and MDA, uric acid, vitamin E and reduced-glutathione (GSH) levels in plasma; MDA, vitamin E, GSH, superoxide-dismutase (SOD), glutathione-peroxidase (GSH-Px) and COMT levels in erythrocytes; vitamin E levels in the platelets of AD patients and control subjects. However, the uric acid levels in plasma and the COMT levels in erythrocytes of AD patients and control subjects with the epsilon4 allele were significantly lower than those observed in control subjects without the epsilon4 allele. Moreover, the duraquinol oxidation level in leukocytes of AD patients with the epsilon4 allele was significantly higher than that in AD patients without the epsilon4 allele and control subjects with and without the epsilon4 allele. The meaning of these results is discussed in terms of involvement of oxidative stress in the etiopathogenesis of AD.

Sarcomatoid squamous cell carcinoma of the uterine cervix: case report.

Sarcomatoid squamous cell carcinoma (SSCC) is a recognized entity, usually involving the upper aerodigestive tract and skin. Location in the lower female genital tract is rare. Only 11 cases have been previously reported, four of which arose in the uterine cervix. The authors describe the case of a 39-years-old woman with SSCC of the uterine cervix in Stage I of the International Federation of Gynecology and Obstetrics (F.I.G.O.) classification. The patient died of disease 12 months after diagnosis. Similar cases described in the literature are also reviewed.