KBG syndrome mimicking genetic generalized epilepsy.

•Several conditions may mimic Genetic Generalized Epilepsy GGE.•GGE is less frequently misdiagnosed compared to other subtypes of epilepsy.•KBG syndrome is a rare autosomal dominant condition.•KBG syndrome may mimic GGE.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) in Ireland.

Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic cause of renal impairment resulting from mutations in the MUC1, UMOD, HNF1B, REN, and SEC61A1 genes. Neither the national or global prevalence of these diseases has been determined. We aimed to establish a database of patients with ADTKD in Ireland and report the clinical and genetic characteristics of these families. Methods: We identified patients via the Irish Kidney Gene Project and referral to the national renal genetics clinic in Beaumont Hospital who met the clinical criteria for ADTKD (chronic kidney disease, bland urinary sediment, and autosomal dominant inheritance). Eligible patients were then invited to undergo genetic testing by a variety of methods including panel-based testing, whole exome sequencing and, in five families who met the criteria for diagnosis of ADTKD but were negative for causal genetic mutations, we analyzed urinary cell smears for the presence of MUC1fs protein. Results: We studied 54 individuals from 16 families. We identified mutations in the MUC1 gene in three families, UMOD in five families, HNF1beta in two families, and the presence of abnormal MUC1 protein in urine smears in three families (one of which was previously known to carry the genetic mutation). We were unable to identify a mutation in 4 families (3 of whom also tested negative for urinary MUC1fs). Conclusions: There are 4443 people with ESRD in Ireland, 24 of whom are members of the cohort described herein. We observe that ADTKD represents at least 0.54% of Irish ESRD patients.

Emergence of multi-resistant Pseudomonas aeruginosa in a Western Australian hospital.

Multi-resistant Pseudomonas aeruginosa (MRPa) has been isolated from patients in a Western Australian teaching hospital with increasing frequency since first encountered in 2006. Between 2006 and 2008 the number of patients with MRPa increased from three to nine per annum, and their location shifted from intensive care to a high dependency unit. A novel water-saving device (aerator) in a staff hand basin was identified as a likely disseminator, with MRPa being isolated from biofilm in the basin's plumbing. The disposal of patient waste, surplus intravenous antibiotic infusions and solid items via hand basins were possible contributory factors. Genotyping of MRPa from patients in other hospitals showed distinct genotypic lineages. The third seasonal cluster persisted for longer, indicating adaption to environment. More effective environmental control of P. aeruginosa is urgently needed.

Biological effects of embedded depleted uranium (DU): summary of armed forces radiobiology research institute research.

The Persian Gulf War resulted in injuries of US Coalition personnel by fragments of depleted uranium (DU). Fragments not immediately threatening the health of the individuals were allowed to remain in place, based on long-standing treatment protocols designed for other kinds of metal shrapnel injuries. However, questions were soon raised as to whether this approach is appropriate for a metal with the unique radiological and toxicological properties of DU. The Armed Forces Radiobiology Research Institute (AFRRI) is investigating health effects of embedded fragments of DU to determine whether current surgical fragment removal policies remain appropriate for this metal. These studies employ rodents implanted with DU pellets as well as cultured human cells exposed to DU compounds. Results indicate uranium from implanted DU fragments distributed to tissues far-removed from implantation sites, including bone, kidney, muscle, and liver. Despite levels of uranium in the kidney that were nephrotoxic after acute exposure, no histological or functional kidney toxicity was observed. However, results suggest the need for further studies of long-term health impact, since DU was found to be mutagenic, and it transformed human osteoblast cells to a tumorigenic phenotype. It also altered neurophysiological parameters in rat hippocampus, crossed the placental barrier, and entered fetal tissue. This report summarizes AFRRI's depleted uranium research to date.

Radioprotective and locomotor responses of mice treated with nimodipine alone and in combination with WR-151327.

The effect of combining a radiation-protective phosphorothioate with another agent was investigated in an attempt to increase radioprotection and reduce toxicity. The calcium channel blocker nimodipine (NIMO) was administered alone (1 or 10 mg kg-1) or in combination with 200 mg kg-1 of the phosphorothioate radioprotector WR-151327 (WR) (S-3-(3-methylaminopropylamino)propylphosphorothioic acid). Radioprotection as measured (30-day survival) of mice treated i.p. 30 min before (60)Co irradiation at a dose rate of 1 Gy min-1 was evaluated in CD2F1 male mice. The effects of nimodipine and WR-151327 on locomotor activity were investigated also in a separate group of non-irradiated mice. The LD(50/30) for the Emulphor vehicle control group was 8.56. For nimodipine alone (1 or 10 mg kg-1) the LD(50/30)was 8.39 and 10.21 Gy, respectively, yielding dose modification factors (DMFs) of 0.98 and 1.19, respectively. When WR-151327 was given alone, the

The effects of prenatal cocaine exposure on dopaminergic challenge and receptor binding in Wistar rats.

The behavioral teratogenic effects of prenatal cocaine administration in Wistar rats were assessed in dams treated throughout gestation via oral gavage with either 0 or 80 mg/kg of cocaine. A pair-fed (PF) cohort group for the 80-mg/kg dose was used to control for an anorexic effect of cocaine. Alterations in the dopaminergic system at maturity were evaluated using pharmacological challenges with amphetamine and cocaine and by measuring D1 and D2 receptor binding in the nucleus accumbens and caudate nucleus. No significant difference among the offspring of the treatment groups was found in amphetamine-induced locomotion. A cocaine-based conditioned taste aversion was established in all offspring, but no significant effect of prenatal cocaine treatment was seen. Dopamine receptor binding was not significantly influenced by prenatal treatment, although a decreased D1 binding in the caudate nucleus of the prenatal cocaine rats approached significance.

Behavioral effects of vehicles: DMSO, ethanol, Tween-20, Tween-80, and emulphor-620.

Experimental drugs and compounds that do not easily dissolve in water or saline are frequently combined with vehicles like solvents, detergents, or vegetable oils. Yet very little has been reported on the behavioral effects of vehicles. In this study, we assessed the effects of a vegetable oil (emulphor-620), two detergents (Tween-20 and Tween-80), and two solvents [dimethyl sulphoxide (DMSO) and ethanol] on the locomotor activity in CD2F1 male mice. Locomotor activity was monitored for 12 h after vehicle administration (IP). The concentrations for each vehicle were expressed as percent of vehicle in saline (v/v). Emulphor-620 did not affect locomotor activity at any concentration tested (2%, 4%, 8%, 16%, and 32%). Tween-20 significantly decreased locomotor activity at a concentration of 16% and Tween-80 at 32%. DMSO significantly decreased locomotor activity at concentrations of 32% and 64%. In contrast, ethanol produced a biphasic behavioral response: increased activity at a concentration of 16% and decreased activity at a concentration of 32%. These results will facilitate the selection and concentration of vehicles to be used in combination with experimental drugs or test agents.

Testosterone implantation reduces the motor effects of cocaine.

The abuse of anabolic-androgenic steroids noted in recent years has been correlated with an increased likelihood of abuse of other drugs, including cocaine. This research was designed to investigate whether manipulation of androgen levels would alter the unconditioned behavioral effects of cocaine. The influence of testosterone on the locomotor activating effect of oral cocaine was evaluated. Subjects were male gonadally intact and castrated Wistar rats, implanted s.c. with either placebo or 100mg testosterone 30-day pellets. Beginning 7 days after pellet implantation, each animal in the four subgroups randomly received 0, 20, 40 and 80mg/kg cocaine (once, each dose). Cocaine 80mg/kg significantly enhanced locomotor activity in all groups except the intact testosterone-treated group. Of the four groups, this subgroup would have the highest plasma level of testosterone. These data suggest that chronic exogenous androgen administration may reduce the behavioral effects of cocaine.

Absence of a surface-connected canalicular system in bovine platelets.

Human platelets possess a surface-connected canalicular system (SCCS) which has been postulated to subserve endocytosis as well as secretion. Platelets of most animal species studied to date, including those of cattle, function similarly. However, ultrastructural analysis of freeze-fractured bovine platelets or thin sectioned bovine platelets treated with electron-dense tracers failed to delineate a SCCS. This observation may throw an entirely new light on the role of this organelle.