Epileptic crisis during and after cerebrovascular diseases. A clinical analysis of 78 cases]

Seventy-eight patients with post-stroke seizures were studied retrospectively to determine the clinical, EEG and CT features of these seizures and their prognosis. There were 57 cerebral infarctions and 21 hemorrhages. Twenty-eight (36%) initial seizures occurred within one month after the stroke (0-24 hours in 19 cases) and were classified as early-onset seizures. Fifty (64%) initial seizures occurred more than 3 months after the stroke (3-12 months in 33 cases) and were classified as late-onset seizures. Compared with a population of 1938 strokes admitted during the same period, the proportion of patients with alcohol abuse, infarction in the anterior cerebral artery territory, watershed infarcts and lobar haemorrhages was significantly greater in our series. The proportion did not vary with the nature of the stroke (infarction or hemorrhage), except for early onset seizures in which the proportion of hemorrhages was significantly greater. Nor did it vary with the cause of hemispheric infarctions (cardioembolism or atherothrombosis or others). Ninety-five percent of the lesions affected the cerebral cortex or the subcortical white matter or both. Of all 78 initial seizures, 64% were partial motor (simple or secondarily generalized); 32% were primarily generalized, and 4% were partial not motor; status epilepticus was seen in 14% of the cases. An initial EEG, performed in 76 patients was normal in 7. Among the remaining 69 patients EEG showed focal or diffuse slowing down in 63% and epileptic features in 37% (including 10 cases of PLEDs). Early post-seizure EEG and repeated recordings significantly increased the specificity of EEG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Does HIV infection contribute to increased beta-amyloid synthesis and plaque formation leading to neurodegeneration and Alzheimer’s disease?

Journal of NeuroVirology - HIV infection in the combination antiretroviral therapy (cART) era has become a chronic disease with a life expectancy almost identical to those free from this infection....     

Chemical profiles with cardioprotective and anti-depressive effects of Morus macroura Miq. leaves and stem branches dichloromethane fractions on isoprenaline induced post-MI depression

This study was conducted to explore the potential cardioprotective and anti-depressive effects of dichloromethane (DCM) fractions of Morus macroura leaves (L) and stem branches (S) on post-myocardial infarction (MI) depression induced by isoprenaline (ISO) in rats in relation to their metabolites. The study was propped with a UPLC-ESI-MS/MS profiling and chromatographic isolation of the secondary metabolites. Column chromatography revealed the isolation of lupeol palmitate (6) that was isolated for the first time from nature with eight known compounds. In addition, more than forty metabolites belonging, mainly to flavonoids, and anthocyanins groups were identified. The rats were injected with ISO (85 mg kg⁻¹, s.c) in the first two days, followed by the administration of M. macroura DCM-L and DCM-S fractions (200 mg kg⁻¹ p.o) for 19 days. Compared with the ISO exposed rats, the treated rats displayed a reduction in cardiac biomarkers (LDH and CKMB), anxiety, and depressive-like behaviour associated with an increase in the brain defense system (SOD and GSH), neuronal cell energy, GABA, serotonin, and dopamine, confirmed by histopathological investigations. In conclusion, DCM-L and DCM-S fractions'' cardioprotective and anti-depressive activities are attributed to their metabolite profile. Therefore, they could serve as a potential agent in amending post-MI depression.

This study was conducted to explore the potential cardioprotective and anti-depressive effects of dichloromethane fractions of Morus macroura leaves and stem branches on post-myocardial infarction depression induced by isoprenaline in rats in relation to their metabolites.     

Identification and characterization of the capsular polysaccharide (K-antigen) locus of Porphyromonas gingivalis

Capsular polysaccharides of gram-negative bacteria play an important role in maintaining the structural integrity of the cell in hostile environments and, because of their diversity within a given species, can act as useful taxonomic aids. In order to characterize the genetic locus for capsule biosynthesis in the oral gram-negative bacterium Porphyromonas gingivalis, we analyzed the genome of P. gingivalis W83 which revealed two candidate loci at PG0106-PG0120 and PG1135-PG1142 with sufficient coding capacity and appropriate gene functions based on comparisons with capsule-coding loci in other bacteria. Insertion and deletion mutants were prepared at PG0106-PG0120 in P. gingivalis W50-a K1 serotype. Deletion of PG0109-PG0118 and PG0116-PG0120 both yielded mutants which no longer reacted with antisera to K1 serotypes. Restriction fragment length polymorphism analysis of the locus in strains representing all six K-antigen serotypes and K(-) strains demonstrated significant variation between serotypes and limited conservation within serotypes. In contrast, PG1135-PG1142 was highly conserved in this collection of strains. Sequence analysis of the capsule locus in strain 381 (K(-) strain) demonstrated synteny with the W83 locus but also significant differences including replacement of PG0109-PG0110 with three unique open reading frames, deletion of PG0112-PG0114, and an internal termination codon within PG0106, each of which could contribute to the absence of capsule expression in this strain. Analysis of the Arg-gingipains in the capsule mutants of strain W50 revealed no significant changes to the glycan modifications of these enzymes, which indicates that the glycosylation apparatus in P. gingivalis is independent of the capsule biosynthetic machinery.     

Consanguinity-associated kidney diseases in Lebanon: an epidemiological study

Consanguineous marriages are common in many countries of the Middle East including Lebanon. Their impact on the repartition of kidney diseases and on the risk for familial nephritis is not known. We surveyed all of the dialysis centers in Lebanon. Nine hundred and twenty-five (925) patients and their private physicians were asked to answer a questionnaire. More than half of the hemodialysis (HD) patients had an unknown etiology of their kidney disease. Diabetes, polycystic kidney disease (PKD), chronic pyelonephritis and nephrosclerosis (NS) were the most commonly documented diagnoses. Consanguinity was present in 26% of the total HD population. More consanguineous patients with unknown renal etiology were diagnosed with their kidney diseases and initiated on dialysis before the age of 30 when compared with their non-consanguineous counter-parts (45% versus 33%, P<0.02 and 42% versus 27%, P<0.01), respectively. Similarly, consanguineous polycystic patients were diagnosed and started earlier on dialysis when compared with the non-consanguineous population (34% versus 12%, P<0.05 and 28% versus 8%, P<0.05), respectively suggesting a different disease pattern. Furthermore, the risk for family history of kidney disease was noticeable in the non-consanguineous population and significantly higher among the consanguineous patients (12% versus 18%, P<0.04). Consanguinity-associated kidney diseases affected all religious communities, in particular the Muslim and the Druze (36 and 39%), respectively versus 17% of the Christian community. Certain geographical areas were more involved than others such as the North, South and the Bekaa with the highest percentage (40%) in the latter. Socio-economical level was not a contributing factor. We conclude that the documentation of the underlying etiology in end-stage renal diseases (ESRD) seems to be deficient. Furthermore, consanguinity is prevalent in the Lebanese dialysis patients population, in particular the Muslim and the Druze communities. Consanguinity-associated kidney diseases pattern seems to differ from that of the general HD population by disease diagnosis and initiation at a younger age and a significantly higher risk for familial renal disease. It is a cultural phenomenon prevalent predominantly in the rural areas. We recommend a multi-approach including educational, informative and probably legislative strategy in order to limit and hopefully discourage consanguineous marriages.     

Paradoxical effects of interleukin-10 on the maturation of murine myeloid dendritic cells

The immunoregulatory cytokine, interleukin-10 (IL-10), has been shown to inhibit the maturation of human myeloid dendritic cells (DC). In the present study, we demonstrate that IL-10 has paradoxical effects on the maturation of murine myeloid bone marrow-derived DC. On the one hand, IL-10 inhibits the maturation of murine myeloid DC. The addition of IL-10 to granulocyte-macrophage colony-stimulating factor (GM-CSF)-supported murine BM-derived DC cultures reduced the frequency of major histocompatibility complex (MHC) class IIbright cells. These IL-10-pretreated DC have a reduced capacity to stimulate T cells in an allogeneic mixed leucocyte reaction. On the other hand, however, and in contrast to the effects of IL-10 on human DC, we found that the addition of IL-10 from the initiation of the culture onwards induced an up-regulation of the expression of the costimulatory molecules CD40, CD80 and CD86 on murine myeloid DC, as compared to DC generated with GM-CSF only. Moreover, a subpopulation of IL-10-pretreated MHC class IIdim DC lacked the capacity to take up dextran-fluorescein isothiocyanate (FITC), a feature of DC maturation. Taken together, our data demonstrate that the generation of murine myeloid DC in the presence of IL-10 results in a population of incompletely matured MHC class IIdim CD80+ CD86+ DC. These DC lack T-cell stimulatory capacity, suggesting a role for IL-10 in conferring tolerogenic properties on murine myeloid DC.     

T-cell-specific deletion of STIM1 and STIM2 protects mice from EAE by impairing the effector functions of Th1 and Th17 cells

T-cell function is dependent on store-operated Ca(2+) influx that is activated by the stromal interaction molecules (STIM) 1 and 2. We show that mice with T-cell-specific deletion of STIM1 or STIM2 are protected from EAE, a mouse model of multiple sclerosis (MS). While STIM1- and STIM2-deficient T cells could be successfully primed by autoantigen, they failed to produce the proinflammatory cytokines IL-17 and IFN-γ. STIM1-deficient T cells showed reduced expression of IL-23R, required for Th17 cell homeostasis, and had impaired chemokine-dependent T-cell migration caused by a lack of chemokine-induced Ca(2+) influx. Autoantigen-specific STIM1- or STIM2-deficient T cells failed to expand and accumulate in the CNS and lymph nodes following adoptive transfer to passively induce EAE, suggesting that autoantigen-specific restimulation or homeostasis of STIM1- and STIM2-deficient T cells are impaired. Combined deletion of both STIM1 and STIM2, previously shown to impair Treg development and function, completely protected mice from EAE. This indicates that, in the absence of Ca(2+) influx, autoreactive T cells are severely dysfunctional rendering Treg dispensable for the prevention of CNS inflammation. Our findings demonstrate that both STIM1 and STIM2 are critical for T-cell function and autoimmunity in vivo.     

Comparison of real-time PCR and culture for detection of Porphyromonas gingivalis in subgingival plaque samples

Porphyromonas gingivalis is a major pathogen in destructive periodontal disease in humans. Detection and quantification of this microorganism are relevant for diagnosis and treatment planning. The prevalence and quantity of P. gingivalis in subgingival plaque samples of periodontitis patients were determined by anaerobic culture and real-time PCR amplification of the 16S small-subunit rRNA gene. The PCR was performed with primers and a fluorescently labeled probe specific for the P. gingivalis 16S rRNA gene. By the real-time PCR assay, as few as 1 CFU of P. gingivalis could be detected. Subgingival plaque samples from 259 adult patients with severe periodontitis were analyzed. P. gingivalis was detected in 111 (43%) of the 259 subgingival plaque samples by culture and in 138 (53%) samples by PCR. The sensitivity, specificity, and positive and negative predictive values of the real-time PCR were 100, 94, 94, and 100%, respectively. We conclude that real-time PCR confirms the results of quantitative culture of P. gingivalis and offers significant advantages with respect to the rapidity and sensitivity of detection of P. gingivalis in subgingival plaque samples.     

Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1

Longitudinal studies in Sudan show ethnic differences in incidence and clinical phenotypes associated with Leishmania donovani. Immunologically, bias in type 1 vs type 2 cytokine responses is important. To determine whether polymorphisms at IL4/IL9 or IFNGR1 contribute to susceptibility, we examined 59 multicase families of visceral leishmaniasis (VL) with/without post Kala-azar dermal leishmaniasis (PKDL). Multipoint nonparametric analysis (Allegro) linked IL4/IL9 to VL per se (P=0.002). Transmission disequilibrium testing with robust variance estimates confirmed association in the presence of linkage between VL per se and IL4 (P=0.008) but not IL9. Stepwise logistic regression analysis showed both IL4RP2 and IL4RP1 markers contributed significantly to the association, suggesting a common disease-associated haplotype. In contrast, IFNGR1 was linked (P=0.031) and associated (P=0.007) to PKDL but not VL or VL per se. Hence, polymorphism in a type 2 cytokine gene influences underlying susceptibility to VL, whereas IFNGR1 is specifically related to susceptibility to PKDL.