Novel Neurovascular Protective Agents: Effects of INV-155, INV-157, INV-159, and INV-161 versus Lipoic Acid and Captopril in a Rat Stroke Model

Background. Lipoic acid (LA), which has significant antioxidant properties, may also function as a potent neuroprotectant. The synthetic compounds INV-155, INV-157, INV-159, and INV-161 are physiochemical combinations of lipoic acid and captopril. We sought to determine if these compounds have neuroprotective potential following middle cerebral artery occlusion (MCAO) in rats. Methods. Male Sprague-Dawley rats were injected intravenously with captopril (1–50 mg/kg) 30 minutes prior to MCAO. Blood pressure, heart rate, baroreceptor reflex sensitivity, and infarct size were measured. In addition, dose response effect on infarct size and cardiovascular parameters was determined using INV-155, INV-157, INV-159, and INV-161 and compared to captopril and LA. Results. Pretreatment with captopril and LA at all doses tested was neuroprotective. The compounds INV-159 (0.5–10 mg/kg) and INV-161 (1–10 mg/kg) produced a significant,dose-dependent decrease in infarct size. In contrast, INV-155 and INV-157 had no effect on infarct size. Conclusions. Combined pretreatment with captopril potentiated the neuroprotective benefit observed following LA alone. Both INV-159 and INV-161 were also neuroprotective. These results suggest that patients taking combinations of captopril and LA, either as combination therapy or in the form of INV-159 or INV-161, may also benefit from significant protection against cerebral infarction

Histological and immunological correlates of suspected leprosy lesions

Thirty-two subjects with suspected leprosy lesions were investigated to assess various modalities of sensibility and sweatfunction and these were correlated with immunological and histological parameters. It was found that pain and temperature, mediated by small unmyelinated fibres were impaired in the early lesions. Impairment of sweat function was seen only when one of the modalities of sensibility was also affected Antibodies specific to a protein (35 kDa) antigen and phenolic glycolipid 1 of Mycobacterium leprae were positive in nine and 12 cases respectively, while 15 of the 31 biopsies revealed the presence of mycobacterial antigens in these lesions. The implications of these findings are discussed

Bianchi type I universe with viscous fluid: A qualitative analysis

The nature of cosmological solutions for a homogeneous, anisotropic Universe given by a Bianchi type-I (BI) model in the presence of a Cosmological constant $\Lambda$ is investigated by taking into account dissipative process due to viscosity. The system in question is thoroughly studied both analytically and numerically. It is shown the viscosity, as well as the $\Lambda$ term exhibit essential influence on the character of the solutions. In particular a negative $\Lambda$ gives rise to an ever-expanding Universe, whereas, a suitable choice of initial conditions plus a positive $\Lambda$ can result in a singularity-free oscillatory mode of expansion. For some special cases it is possible to obtain oscillations in the exponential mode of expansion of the BI model even with a negative $\Lambda$, where oscillations arise by virtue of viscosity.Comment: RevTex, 16 pages, 32 figure

Genetic diversity of Mycobacterium tuberculosis isolates from central India

Background & objectives: There is a paucity of data available on genetic biodiversity of Mycobacterium tuberculosis isolates from central India. The present study was carried out on isolates of M. tuberculosis cultured from diagnostic clinical samples of patients from Bhopal, central India, using spoligotyping as a method of molecular typing. Methods: DNA was extracted from 340 isolates of M. tuberculosis from culture, confirmed as M. tuberculosis by molecular and biochemical methods and subjected to spoligotyping. The results were compared with the international SITVIT2 database. Results: Sixty five different spoligo international type (SIT) patterns were observed. A total of 239 (70.3%) isolates could be clustered into 25 SITs. The Central Asian (CAS) and East African Indian (EAI) families were found to be the two major circulating families in this region. SIT26/CAS1_DEL was identified as the most predominant type, followed by SIT11/EAI3_IND and SIT288/CAS[2]. Forty (11.8%) unique (non-clustered) and 61 (17.9%) orphan isolates were identified in the study. There was no significant association of clustering with clinical and demographic characteristics of patients. Interpretation & conclusions: Well established SITs were found to be predominant in our study. SIT26/CAS1_DEL was the most predominant type. However, the occurrence of a substantial number of orphan isolates may indicate the presence of active spatial and temporal evolutionary dynamics within the isolates of M. tuberculosis

Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder : differential involvement of immune-related gene loci

J. Saarela työryhmäjäsen.Peer reviewe

Hyperactivity, impulsivity, and inattention in boys with cleft lip and palate: relationship to ventromedial prefrontal cortex morphology

The purpose of this study is to evaluate quantitative structural measures of the ventromedial prefrontal cortex (vmPFC) in boys with isolated clefts of the lip and/or palate (ICLP) relative to a comparison group and to associate measures of brain structure with quantitative measures of hyperactivity, impulsivity, and inattentiveness. A total of 50 boys with ICLP were compared to 60 healthy boys without clefts. Magnetic resonance imaging brain scans were used to evaluate vmPFC structure. Parents and teachers provided quantitative measures of hyperactivity, impulsivity, and inattentiveness using the Pediatric Behavior Scale. Boys with ICLP had significantly higher ratings of hyperactivity/impulsivity/inattention (HII) and significantly increased volume of the right vmPFC relative to the comparison group. There was a direct relationship between HII score and vmPFC volume in both the ICLP group and control group, but the relationship was in the opposite direction: in ICLP, the higher the vmPFC volume, the higher the HII score; for the comparison group, the lower the vmPFC volume, the greater the HII score. The vmPFC is a region of the brain that governs behaviors of hyperactivity, impulsivity and inattention (HII). In boys with ICLP, there are higher levels of HII compared to the controls and this is directly related to a significantly enlarged volume of the right vmPFC. Enlargement of this region of the brain is therefore considered to be pathological in the ICLP group and supports the notion that abnormal brain structure (from abnormal brain development) is the underlying etiology for the abnormal behaviors seen in this population

ESKIMO1 Disruption in Arabidopsis Alters Vascular Tissue and Impairs Water Transport

Water economy in agricultural practices is an issue that is being addressed through studies aimed at understanding both plant water-use efficiency (WUE), i.e. biomass produced per water consumed, and responses to water shortage. In the model species Arabidopsis thaliana, the ESKIMO1 (ESK1) gene has been described as involved in freezing, cold and salt tolerance as well as in water economy: esk1 mutants have very low evapo-transpiration rates and high water-use efficiency. In order to establish ESK1 function, detailed characterization of esk1 mutants has been carried out. The stress hormone ABA (abscisic acid) was present at high levels in esk1 compared to wild type, nevertheless, the weak water loss of esk1 was independent of stomata closure through ABA biosynthesis, as combining mutant in this pathway with esk1 led to additive phenotypes. Measurement of root hydraulic conductivity suggests that the esk1 vegetative apparatus suffers water deficit due to a defect in water transport. ESK1 promoter-driven reporter gene expression was observed in xylem and fibers, the vascular tissue responsible for the transport of water and mineral nutrients from the soil to the shoots, via the roots. Moreover, in cross sections of hypocotyls, roots and stems, esk1 xylem vessels were collapsed. Finally, using Fourier-Transform Infrared (FTIR) spectroscopy, severe chemical modifications of xylem cell wall composition were highlighted in the esk1 mutants. Taken together our findings show that ESK1 is necessary for the production of functional xylem vessels, through its implication in the laying down of secondary cell wall components