Early motor and electrophysiological changes in transgenic mouse model of amyotrophic lateral sclerosis and gender differences on clinical outcome

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disorder affecting motoneurons and the SOD1(G93A) transgenic mice are widely employed to study disease physiopathology and therapeutic strategies. Despite the cellular and biochemical evidences of an early motor system dysfunction, the conventional behavioral tests do not detect early motor impairments in SOD1 mouse model. We evaluated early changes in motor behavior of ALS mice by doing the analyses of tail elevation, footprint, automatic recording of motor activities by means of an infrared motion sensor activity system and electrophysiological measurements in male and female wild-type (WT) and SOD1(G93A) mice from postnatal day (P) 20 up to endpoint. The classical evaluations of mortality, weight loss, tremor, rotometer, hanging wire and inclined plane were also employed. There was a late onset (after P90) of the impairments of classical parameters and the outcome varied between genders of ALS mice, being tremor, cumulative survival, weight loss and neurological score about 10 days earlier in male than female ALS mice and also about 20 days earlier in ALS males regarding rotarod and hanging wire performances. While diminution of hindpaw base was 10 days earlier in ALS males (P110) compared to females, the steep length decreased 40 days earlier in ALS females (P60) than ALS males. The automatic analysis of motor impairments showed substantial late changes (after P90) of motility and locomotion in the ALS females, but not in the ALS males. It was surprising that the scores of tail elevation were already decreased in ALS males and females by P40, reaching the minimal values at the endpoint. The electrophysiological analyses showed early changes of measures in the ALS mouse sciatic nerve, i.e., decreased values of amplitude (P40) and nerve conduction velocity (P20), and also an increased latency (P20) reaching maximal level of impairments at the late disease phase. The early changes were not accompanied by reductions of neuronal protein markers of neurofilament 200 and ChAT in the ventral part of the lumbar spinal cord of P20 and P60 ALS mice by means of Western blot technique, despite remarkable decreases of those protein levels in P120 ALS mice. In conclusion, early changes of motor behavior and electrophysiological parameters in ALS mouse model must be taken into attention in the analyses of disease mechanisms and therapeutic effects. (C) 2011 Published by Elsevier B.V.

Classification System of Raman Spectra using Cluster Analysis to Diagnose Coronary Artery Lesions

The traditional methods employed to detect atherosclerotic lesions allow for the identification of lesions; however, they do not provide specific characterization of the lesion`s biochemistry. Currently, Raman spectroscopy techniques are widely used as a characterization method for unknown substances, which makes this technique very important for detecting atherosclerotic lesions. The spectral interpretation is based on the analysis of frequency peaks present in the signal; however, spectra obtained from the same substance can show peaks slightly different and these differences make difficult the creation of an automatic method for spectral signal analysis. This paper presents a signal analysis method based on a clustering technique that allows for the classification of spectra as well as the inference of a diagnosis about the arterial wall condition. The objective is to develop a computational tool that is able to create clusters of spectra according to the arterial wall state and, after data collection, to allow for the classification of a specific spectrum into its correct cluster.

Ethnicity and Arterial Stiffness in Brazil

BACKGROUND The impact of increased central arterial stiffness as a predictor of morbidity and mortality, independently of other cardiovascular (CV) risk factors, has been established. The main aim of the present work was to investigate the association of ethnicity on arterial stiffness in different ethnic groups from the Brazilian population. METHODS A total of 1,427 individuals from the general population were randomly selected from the Vitoria City metropolitan area and 588 Amerindians from a native community in Brazil. The ethnicity of the general population was classified by a standard questionnaire as Caucasian descent, African descent, or Mulattos (considered racially mixed subjects). Pulse wave velocity (PWV) was measured with a noninvasive automatic device (Complior, Colson; Garges les Gonesses, France). RESULTS Hemodynamic data of PWV, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) was higher in African descent individuals than in the other groups (P < 0.001). These results were still observed after adjustment for age and mean arterial pressure (P < 0.001). In addition, studying only normotensive individuals, PWV adjusted levels were higher in African descent individuals, and lower in Amerindians when compared with other ethnic groups (P < 0.01), showing, without the possible confounder effects of time and severity of hypertension or medication use, that PWV is associated with ethnicity in our population. CONCLUSION The study of different ethnic groups from a highly admixtured population was able to demonstrate an association between ethnicity and arterial stiffness.

APOE polymorphism is associated with lipid profile, but not with arterial stiffness in the general population

Background: Cardiovascular diseases (CVD) are the main cause of death and disability in developed countries. In most cases, the progress of CVD is influenced by environmental factors and multifactorial inheritance. The purpose of this study was to investigate the association between APOE genotypes, cardiovascular risk factors, and a noninvasive measure of arterial stiffness in the Brazilian population. Methods: A total of 1493 urban Brazilian individuals were randomly selected from the general population of the Vitoria City Metropolitan area. Genetic analysis of the APOE polymorphism was conducted by PCR-RFLP and pulse wave velocity analyzed with a noninvasive automatic device. Results: Age, gender, body mass index, triglycerides, creatinine, uric acid, blood glucose, blood pressure phenotypes were no different between epsilon 2, epsilon 3 and epsilon 4 alleles. The epsilon 4 allele was associated with higher total-cholesterol (p < 0.001), LDL-C (p < 0.001), total-cholesterol/HDL-C ratio (p < 0.001), LDL/HDL-C ratio (p < 0.001), lower HDL-C values (p < 0.001) and higher risk to obesity (OR = 1.358, 95% CI = 1.019-1.811) and hyperuricemia (OR = 1.748, 95% CI = 1.170-2.611). Nevertheless, pulse wave velocity (p = 0.66) measures were no different between genotypes. The significant association between APOE genotypes and lipid levels persisted after a 5-year follow-up interval, but no interaction between time and genotype was observed for lipids longitudinal behavior. Conclusion: The epsilon 4 allele of the APOE gene is associated with a worse lipid profile in the Brazilian urban population. In our relatively young sample, the observed effect of APOE genotype on lipid levels was not translated into significant effects in arterial wall stiffness.

Abnormally increased effective connectivity between parahippocampal gyrus and ventromedial prefrontal regions during emotion labeling in bipolar disorder

Emotional liability and mood dysregulation characterize bipolar disorder (BID), yet no study has examined effective connectivity between parahippocampal gyrus and prefrontal cortical regions in ventromedial and dorsal/lateral neural systems subserving mood regulation in BD. Participants comprised 46 individuals (age range: 18-56 years): 21 with a DSM-IV diagnosis of BID, type I currently remitted; and 25 age- and gender-matched healthy controls (HC). Participants performed an event-related functional magnetic resonance imaging paradigm, viewing mild and intense happy and neutral faces. We employed dynamic causal modeling (I)CM) to identify significant alterations in effective connectivity between BD and HC. Bayes model selection was used to determine the best model. The right parahippocampal gyrus (PHG) and right subgenual cingulate gyrus (sgCG) were included as representative regions of the ventromedial neural system. The right dorsolateral prefrontal cortex (DLPFC) region was included as representative of the dorsal/lateral neural system. Right PHG-sgCG effective connectivity was significantly greater in BD than HC, reflecting more rapid, forward PHG-sgCG signaling in BD than HC. There was no between-group difference in sgCG-DLPFC effective connectivity. In BD, abnormally increased right PHG-sgCG effective connectivity and reduced right PHG activity to emotional stimuli suggest a dysfunctional ventromedial neural system implicated in early stimulus appraisal, encoding and automatic regulation of emotion that may represent a pathophysiological functional neural mechanism for mood dysregulation in BD. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Antidepressants, suicidality and rebound effect: evidence of similitude?

Background: Samuel Hahnemann noticed that palliative treatments for the symptoms of chronic diseases, after an initial improvement, provoked symptoms similar but stronger symptoms to those initially suppressed. He regarded this as a consequence of the vital reaction of the organism: an automatic and instinctive capacity to return to the initial health condition altered by medicines. Using this homeostatic conception of the organism as a treatment rationale, Hahnemann proposed the therapy of similarity, administering to the patients medicines capable of causing, in healthy individuals, similar symptoms to the natural disease. Based on experimental observations, he proposed that the primary action of the drug was followed by the secondary and opposite action of the organism, inaugurating homeopathic pharmacology, and alerting to the harmful consequences of palliative medicines in susceptible individuals. Such liatrogenic events can be observed in contemporary medicine, after the withdrawal of modern enantiopathic medicines, according to the study of the rebound effect or paradoxical reaction of the organism. Method. This study reviews the recent studies which describe suicidallity after the suspension or discontinuation of second generation antidepressants according to the hypothesis of the paradoxical reaction of the organism. Conclusions: Rebound and withdrawal effects, including suicidality occur with antidepressant drugs. They are relatively rare but more intense than the primary action of the drug. The probability of such effects is influenced by patient factors including age and diagnosis, and drug factors including half-life. Homeopathy (2009) 98, 114-121.

Loss-of-function mutations in the genes encoding prokineticin-2 or prokineticin receptor-2 cause autosomal recessive Kallmann syndrome

Context: Physiological activation of the prokineticin pathway has a critical role in olfactory bulb morphogenesis and GnRH secretion in mice. Objective: To investigate PROK2 and PROKR2 mutations in patients with hypogonadotropic hypogonadism (HH) associated or not with olfactory abnormalities. Design: We studied 107 Brazilian patients with HH (63 with Kallmann syndrome and 44 with normosmic HH) and 100 control individuals. The coding regions of PROK2 and PROKR2 were amplified by PCR followed by direct automatic sequencing. Results: In PROK2, two known frameshift mutations were identified. Two brothers with Kallmann syndrome harbored the homozygous p. G100fsX121 mutation, whereas one male with normosmic HH harbored the heterozygous p. I55fsX56 mutation. In PROKR2, four distinct mutations (p. R80C, p. Y140X, p. L173R, and p. R268C) were identified in five patients with Kallmann syndrome and in one patient with normosmic HH. These mutations were not found in the control group. The p. R80C, p. L173R, and p. R268C missense mutations were identified in the heterozygous state in the HH patients and in their asymptomatic first-degree relatives. In addition, nomutations of FGFR1, KAL1, GnRHR, KiSS-1, or GPR54 were identified in these patients. Notably, the new nonsense mutation (p. Y140X) was identified in the homozygous state in an anosmic boy with micropenis, bilateral cryptorchidism, and high-arched palate. His asymptomatic parents were heterozygous for this severe defect. Conclusion: We expanded the repertoire of PROK2 and PROKR2 mutations in patients with HH. In addition, we show that PROKR2 haploinsufficiency is not sufficient to cause Kallmann syndrome or normosmic HH, whereas homozygous loss-of-function mutations either in PROKR2 or PROK2 are sufficient to cause disease phenotype, in accordance with the Prokr2 and Prok2 knockout mouse models.

Radon-domain detection of the nipple and the pectoral muscle in mammograms

In this paper, methods are presented for automatic detection of the nipple and the pectoral muscle edge in mammograms via image processing in the Radon domain. Radon-domain information was used for the detection of straight-line candidates with high gradient. The longest straight-line candidate was used to identify the pectoral muscle edge. The nipple was detected as the convergence point of breast tissue components, indicated by the largest response in the Radon domain. Percentages of false-positive (FP) and false-negative (FN) areas were determined by comparing the areas of the pectoral muscle regions delimited manually by a radiologist and by the proposed method applied to 540 mediolateral-oblique (MLO) mammographic images. The average FP and FN were 8.99% and 9.13%, respectively. In the detection of the nipple, an average error of 7.4 mm was obtained with reference to the nipple as identified by a radiologist on 1,080 mammographic images (540 MLO and 540 craniocaudal views).