Impact Of Pregabalin Treatment On Synaptic Plasticity And Glial Reactivity During The Course Of Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease that affects young adults. It is characterized by generating a chronic demyelinating autoimmune inflammation in the central nervous system. An experimental model for studying MS is the experimental autoimmune encephalomyelitis (EAE), induced by immunization with antigenic proteins from myelin. The present study investigated the evolution of EAE in pregabalin treated animals up to the remission phase. The results demonstrated a delay in the onset of the disease with statistical differences at the 10th and the 16th day after immunization. Additionally, the walking track test (CatWalk) was used to evaluate different parameters related to motor function. Although no difference between groups was obtained for the foot print pressure, the regularity index was improved post treatment, indicating a better motor coordination. The immunohistochemical analysis of putative synapse preservation and glial reactivity revealed that pregabalin treatment improved the overall morphology of the spinal cord. A preservation of circuits was depicted and the glial reaction was downregulated during the course of the disease. qRT-PCR data did not show immunomodulatory effects of pregabalin, indicating that the positive effects were restricted to the CNS environment. Overall, the present data indicate that pregabalin is efficient for reducing the seriousness of EAE, delaying its course as well as reducing synaptic loss and astroglial reaction.

Engagement of multifocal neural circuits during recall of autobiographical happy events

Happy emotional states have not been extensively explored in functional magnetic resonance imaging studies using autobiographic recall paradigms. We investigated the brain circuitry engaged during induction of happiness by standardized script-driven autobiographical recall in 11 healthy subjects (6 males), aged 32.4 ± 7.2 years, without physical or psychiatric disorders, selected according to their ability to vividly recall personal experiences. Blood oxygen level-dependent (BOLD) changes were recorded during auditory presentation of personal scripts of happiness, neutral content and negative emotional content (irritability). The same uniform structure was used for the cueing narratives of both emotionally salient and neutral conditions, in order to decrease the variability of findings. In the happiness relative to the neutral condition, there was an increased BOLD signal in the left dorsal prefrontal cortex and anterior insula, thalamus bilaterally, left hypothalamus, left anterior cingulate gyrus, and midportions of the left middle temporal gyrus (P < 0.05, corrected for multiple comparisons). Relative to the irritability condition, the happiness condition showed increased activity in the left insula, thalamus and hypothalamus, and in anterior and midportions of the inferior and middle temporal gyri bilaterally (P < 0.05, corrected), varying in size between 13 and 64 voxels. Findings of happiness-related increased activity in prefrontal and subcortical regions extend the results of previous functional imaging studies of autobiographical recall. The BOLD signal changes identified reflect general aspects of emotional processing, emotional control, and the processing of sensory and bodily signals associated with internally generated feelings of happiness. These results reinforce the notion that happiness induction engages a wide network of brain regions.

Hyperglycemia can delay left ventricular dysfunction but not autonomic damage after myocardial infarction in rodents

Background: Although clinical diabetes mellitus is obviously a high risk factor for myocardial infarction (MI), in experimental studies disagreement exists about the sensitivity to ischemic injury of an infarcted myocardium. Recently, our group demonstrated that diabetic animals presented better cardiac function recovery and cellular resistance to ischemic injury than nondiabetics. In the present study, we evaluated the chronic effects of MI on left ventricular (LV) and autonomic functions in streptozotocin (STZ) diabetic rats. Methods: Male Wistar rats were divided into 4 groups: control (C, n = 15), diabetes (D, n = 16), MI (I, n = 21), and diabetes + MI (DI, n = 30). MI was induced 15 days after diabetes (STZ) induction. Ninety days after MI, LV and autonomic functions were evaluated (8 animals each group). Left ventricular homogenates were analyzed by Western blotting to evaluate the expression of calcium handling proteins. Results: MI area was similar in infarcted groups (similar to 43%). Ejection fraction and + dP/dt were reduced in I compared with DI. End-diastolic pressure was additionally increased in I compared with DI. Compared with DI, I had increased Na(+)-Ca(2+) exchange and phospholamban expression (164%) and decreased phosphorylated phospholamban at serine(16) (65%) and threonine(17) (70%) expression. Nevertheless, diabetic groups had greater autonomic dysfunction, observed by baroreflex sensitivity and pulse interval variability reductions. Consequently, the mortality rate was increased in DI compared with I, D, and C groups. Conclusions: LV dysfunction in diabetic animals was attenuated after 90 days of myocardial infarction and was associated with a better profile of calcium handling proteins. However, this positive adaptation was not able to reduce the mortality rate of DI animals, suggesting that autonomic dysfunction is associated with increased mortality in this group. Therefore, it is possible that the better cardiac function has been transitory, and the autonomic dysfunction, more prominent in diabetic group, may lead, in the future, to the cardiovascular damage.

An Extension of the Invariance Principle for a Class of Differential Equations with Finite Delay

An extension of the uniform invariance principle for ordinary differential equations with finite delay is developed. The uniform invariance principle allows the derivative of the auxiliary scalar function V to be positive in some bounded sets of the state space while the classical invariance principle assumes that. V <= 0. As a consequence, the uniform invariance principle can deal with a larger class of problems. The main difficulty to prove an invariance principle for functional differential equations is the fact that flows are defined on an infinite dimensional space and, in such spaces, bounded solutions may not be precompact. This difficulty is overcome by imposing the vector field taking bounded sets into bounded sets.

EXISTENCE RESULTS FOR NEUTRAL INTEGRO-DIFFERENTIAL EQUATIONS WITH UNBOUNDED DELAY

In this paper we discuss the existence of mild, strict and classical solutions for a class of abstract integro-differential equations in Banach spaces. Some applications to ordinary and partial integro-differential equations are considered.

Existence Results for Abstract Partial Neutral Integro-differential Equation with Unbounded Delay

In this paper we study the existence and regularity of mild solutions for a class of abstract partial neutral integro-differential equations with unbounded delay.

In utero protein restriction causes growth delay and alters sperm parameters in adult male rats

Background: Recent studies have supported the concept of ""fetal programming"" which suggests that during the intrauterine development the fetus may be programmed to develop diseases in adulthood. The possible effects of in utero protein restriction on sexual development of rat male offspring were evaluated in the present study. Methods: Pregnant Wistar rats were divided into two experimental groups: one group treated with standard chow (SC, n = 8, 17% protein) and the other group treated with hypoproteic chow (HC, n = 10, 6% protein) throughout gestation. After gestation the two experimental groups received standard chow. To evaluate the possible late reproductive effects of in utero protein restriction, the male offspring of both groups were assessed at different phases of sexual development: prepubertal (30 days old); peripubertal (60 days old); adult (90 days old). Student's t test and Mann-Whitney test were utilized. Differences were considered significant when p < 0.05. Results: We found that in utero protein restriction reduced the body weight of male pups on the first postnatal day and during the different sexual development phases (prepubertal, peripubertal and adult). During adulthood, Sertoli cell number, sperm motility and sperm counts in the testis and epididymal cauda were also reduced in HC. Furthermore, the numbers of sperm presenting morphological abnormalities and cytoplasmic drop retention were higher in HC. Conclusions: In conclusion, in utero protein restriction, under these experimental conditions, causes growth delay and alters male reproductive-system programming in rats, suggesting impairment of sperm quality in adulthood.

Synthesis of PID controllers for a class of time delay systems

In this paper we use the Hermite-Biehler theorem to establish results on the design of proportional plus integral plus derivative (PID) controllers for a class of time delay systems. Using the property of interlacing at high frequencies of the class of systems considered and linear programming we obtain the set of all stabilizing PID controllers. As far as we know, previous results on the synthesis of PID controllers rely on the solution of transcendental equations. This paper also extends previous results on the synthesis of proportional controllers for a class of delay systems Of retarded type to a larger class of delay systems. (C) 2009 Elsevier Ltd. All rights reserved.

Fuzzy risk index for power transformer failures due to external short-circuits

A novel methodology to assess the risk of power transformer failures caused by external faults, such as short-circuit, taking the paper insulation condition into account, is presented. The risk index is obtained by contrasting the insulation paper condition with the probability that the transformer withstands the short-circuit current flowing along the winding during an external fault. In order to assess the risk, this probability and the value of the degree of polymerization of the insulating paper are regarded as inputs of a type-2 fuzzy logic system (T2-FLS), which computes the fuzzy risk level. A Monte Carlo simulation has been used to find the survival function of the currents flowing through the transformer winding during a single-phase or a three-phase short-circuit. The Roy Billinton Test System and a real power system have been used to test the results. (C) 2008 Elsevier B.V. All rights reserved.

Existence results for partial neutral functional differential equations with state-dependent delay

In this paper we study the existence of mild solutions for a class of first order abstract partial neutral differential equations with state-dependent delay. (C) 2008 Elsevier Ltd. All rights reserved.

Delay in the Diagnosis of Cerebral Vein and Dural Sinus Thrombosis Influence on Outcome

Background and Purpose-Diagnostic delay of cerebral vein and dural sinus thrombosis may have an impact on outcome. Methods-In the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) cohort (624 patients with cerebral vein and dural sinus thrombosis), we analyzed the predictors and the impact on outcome of diagnostic delay. Primary outcome was a modified Rankin Scale score > 2 at the end of follow-up. Secondary outcomes were modified Rankin Scale score 0 to 1 at the end of follow-up, death, and visual deficits (visual acuity or visual field). Results-Median delay was 7 days (interquartile range, 3 to 16). Patients with disturbance of consciousness (P < 0.001) and of mental status (P = 0.042), seizure (< 0.001), and with parenchymal lesions on admission CT/MR (P < 0.001) were diagnosed earlier, whereas men (P = 0.01) and those with isolated intracranial hypertension syndrome (P = 0.04) were diagnosed later. Between patients diagnosed earlier and later than the median delay, no statistically significant differences were found in the primary (P = 0.33) and in secondary outcomes: modified Rankin Scale score 0 to 1 (P = 0.86) or deaths (P = 0.53). Persistent visual deficits were more frequent in patients diagnosed later (P = 0.05). In patients with isolated intracranial hypertension syndrome, modified Rankin Scale score > 2 at the end of follow-up was more frequent in patients diagnosed later (P = 0.02). Conclusions-Diagnostic delay was considerable in this cohort and was associated with an increased risk of visual deficit. In patients with isolated intracranial hypertension syndrome, diagnostic delay was also associated with death or dependency. (Stroke. 2009; 40: 3133-3138.)

Novel inactivating mutations in the GH secretagogue receptor gene in patients with constitutional delay of growth and puberty

Background: A limited number of mutations in the GH secretagogue receptor gene (GHSR) have been described in patients with short stature. Objective: To analyze GHSR in idiopathic short stature (ISS) children including a subgroup of constitutional delay of growth and puberty (CDGP) patients. Subjects and methods: The GHSR coding region was directly sequenced in 96 independent patients with ISS, 31 of them with CDGP, in 150 adults, and in 197 children with normal stature. The pharmacological consequences of GHSR non-synonymous variations were established using in vitro cell-based assays. Results: Five different heterozygous point variations in GHSR were identified (c.-6 G>C, c.251G>T (p.Ser84Ile), c.505G>A (p.Ala169Thr), c.545 T>C (p.Val182Ala), and c.1072G>A (p.Ala358Thr)), all in patients with CDGP. Neither these allelic variants nor any other mutations were found in 694 alleles from controls. Functional studies revealed that two of these variations (p.Ser84Ile and p. Val182Ala) result in a decrease in basal activity that was in part explained by a reduction in cell surface expression. The p.Ser84Ile mutation was also associated with a defect in ghrelin potency. These mutations were identified in two female patients with CDGP (at the age of 13 years, their height SDS were -2.4 and -2.3). Both patients had normal progression of puberty and reached normal adult height (height SDS of -0.7 and -1.4) without treatment. Conclusion: This is the first report of GHSR mutations in patients with CDGP. Our data raise the intriguing possibility that abnormalities in ghrelin receptor function may influence the phenotype of individuals with CDGP.

Effects of time delay and transportation on isolation of pathogenic fungi from skin biopsies

BACKGROUND - It is not clear how culture media used during transport and the interval between the biopsy procedure and final processing can affect the successful isolation of fungi. OBJECTIVE - The aim of this study was to investigate the effects of late inoculation of skin biopsies, transported in different sterile fluids, on the isolation rate of pathogenic fungi. METHODS -A total of 278 punch biopsy specimens were collected from 47 patients with suspected lesions of invasive mycoses. Each biopsy was transported in vials with Sabouraud medium with chloramphenicol or saline solution and finally inoculated on Sabouraud agar and 2% chloramphenicol after a 48-72-hour (early) or after 72-hour-7-day (late) interval, comprising four groups of study. RESULTS - The medians of isolation rate of the four sporotrichosis groups were 100%. For paracoccidioidomycosis, the medians ranged from 50% to 84%, with no statistically significant difference among the groups (p=0.88). CONCLUSION - It was concluded that skin biopsies can be transported in Sabouraud medium or saline solution within a 7-day interval from specimen collection up to final inoculation, at room temperature, maintaining viability and growth rate of fungus in culture.