A method to coat plastic catheters with bioactive silver nanoparticles was developed. These catheters are non-toxic and are capable of targeted and sustained release of silver at the implantation site. Because of their demonstrated antimicrobial properties, they may be useful in reducing the risk of infectious complications in patients with indwelling catheters.

Discovered some 35 years ago, succinic semialdehyde dehydrogenase deficiency (SSADHD) represents a rare, autosomal recessively-inherited defect in the second step of the GABA degradative pathway. Some 200 patients have been reported, with broad phenotypic and genotypic heterogeneity. SSADHD represents an unusual neurometabolic disorder in which two neuromodulatory agents, GABA (and the GABA analogue, 4-hydroxybutyrate), accumulate to supraphysiological levels. The unexpected occurrence of epilepsy in several patients is counterintuitive in view of the hyperGABAergic state, in which sedation might be expected. However, the epileptic status of some patients is most likely represented by broader imbalances of GABAergic and glutamatergic neurotransmission. Cumulative research encompassing decades of basic and clinical study of SSADHD reveal a monogenic disease with broad pathophysiological and clinical phenotypes. Numerous metabolic perturbations unmasked in SSADHD include alterations in oxidative stress parameters, dysregulation of autophagy and mitophagy, dysregulation of both inhibitory and excitatory neurotransmitters and gene expression, and unique subsets of SNP alterations of the SSADH gene (so-called ALDH5A1, or aldehyde dehydrogenase 5A1 gene) on the 6p22 chromosomal arm. While seemingly difficult to collate and interpret, these anomalies have continued to open novel pathways for pharmacotherapeutic considerations. Here, we present an update on selected aspects of SSADHD, the ALDH5A1 gene, and future avenues for research on this rare disorder of GABA metabolism.

Background To determine whether familial transmission is shared between autism spectrum disorders and attention-deficit/hyperactivity disorder, we assessed the prevalence, rates of comorbidity, and familial transmission of both disorders in a large population-based sample of children during a recent seven year period. Methods Study participants included all children born to parents with the Kaiser Permanente Northwest (KPNW) Health Plan between January 1, 1998 and December 31, 2004 (n = 35,073). Children and mothers with physician-identified autism spectrum disorders (ASD) and/or attention-deficit/hyperactivity disorder (ADHD) were identified via electronic medical records maintained for all KPNW members. Results Among children aged 6-12 years, prevalence was 2.0% for ADHD and 0.8% for ASD; within those groups, 0.2% of the full sample (19% of the ASD sample and 9.6% of the ADHD sample) had co-occurring ASD and ADHD, when all children were included. When mothers had a diagnosis of ADHD, first born offspring were at 6-fold risk of ADHD alone (OR=5.02, p<0.0001) and at 2.5-fold risk of ASD alone (OR=2.52, p<0.01). Results were not accounted for by maternal age, child gestational age, child gender, and child race. Conclusions ASD shares familial transmission with ADHD. ADHD and ASD have a partially overlapping diathesis.

The modulation of presynaptic voltage-dependent calcium channels by classical second messenger molecules such as protein kinase C and G protein ␤␥ subunits is well established and considered a key factor for the regulation of neurotransmitter release. However, little is known of other endogenous mechanisms that control the activity of these channels. Here, we demonstrate a unique modulation of N-type calcium channels by farnesol, a dephosphorylated intermediate of the mammalian mevalonate pathway. At micromolar concentrations, farnesol acts as a relatively non-discriminatory rapid open channel blocker of all types of high voltage-activated calcium channels, with a mild specificity for Ltype channels. However, at 250 nM, farnesol induces an N-type channel-specific hyperpolarizing shift in channel availability that results in ϳ50% inhibition at a typical neuronal resting potential. Additional experiments demonstrated the presence of farnesol in the brain (rodents and humans) at physiologically relevant concentrations (100 -800 pmol/g (wet weight)). Altogether, our results indicate that farnesol is a selective, high affinity inhibitor of N-type Ca 2؉ channels and raise the possibility that endogenous farnesol and the mevalonate pathway are implicated in neurotransmitter release through regulation of presynaptic voltage-gated Ca 2؉ channels.Calcium entry into the cytosol is a crucial mediator of a range of cellular responses, including cell proliferation and neurotransmitter release (1, 2). Internal calcium levels are precisely regulated through differential expression and modulation of multiple types of voltage-dependent calcium channels (3-6). These channels are key pharmacological targets, and the identification of novel means of regulating calcium channel activity remains of critical importance for the treatment of a variety of neurological disorders, including migraines, pain, and ischemia (7, 8).Molecular cloning has identified genes encoding at least nine different neuronal calcium channel ␣ 1 subunits (termed ␣ 1A through ␣ 1I ). Functional expression studies have shown that ␣ 1A encodes P-and Q-type calcium channels (9, 10); ␣ 1B defines an -conotoxin GVIA-sensitive N-type channel (11, 12); ␣ 1C , ␣ 1D , and ␣ 1F are L-type calcium channels (13-16); ␣ 1G ␣ 1H , and ␣ 1I are members of the family of T-type calcium channels (17-19); and ␣ 1E is a unique calcium channel with properties common to both high and low threshold calcium channels (20,21). The activities of voltage-dependent calcium channels are extensively modulated by cytoplasmic messenger molecules. Although the short-term modulation of these channels by protein kinases (22,23,24) and G protein ␤␥ subunits (25-31) has been well documented, little is known about mechanisms that mediate their long-term regulation.Farnesol is an isoprenoid intermediate of the mevalonate pathway, produced by dephosphorylation of farnesyl pyrophosphate ( Fig. 1) (32, 33). This pathway plays a central role in cell growth and differentiation; controls the production of ub...

Primary as well as secondary hyperparathyroidism may be associated with anemia, and parathyroidectomy (PTx) may improve or even heal it. The precise link between the two conditions is still matter of dicussion. The purpose of the present study was to investigate possible effects of PTx on serum immunoreactive erythropoietin (iEPO) in secondary (group I, n = 23), and primary (group II, n = 16) hyperparathyroidism patients, and in 3 patients undergoing cervicotomy for thyroid mass removal (group III). In group I patients, circulating iEPO levels rose from 23.1 ± 4.8 mU/ml before PTx to 28.2 ± 5.0 and 245 ± 125 mU/ml (mean ± SEM) at day 7 (p = NS) and 14 after PTx (p < 0.003), respectively. Reticulocyte count increased 2 weeks after PTx: from 61,000 ± 13,317 to 86,533 ± 13,462/mm³ (p < 0.05, n = 23). In 4 of these patients serum iEPO levels could be measured again 12–24 months after PTx. They were slightly higher than those determined before PTx: 37.0 ± 8.4 versus 31.8 ± 13.5 mU/ml. Their hematocrits were also higher than before PTx: 12.8 ± 0.9 versus 11.0 ± 0.9 g/dl. In group II patients, serum iEPO levels remained unchanged after PTx: 17.5 ± 2.0 mU/ml before PTx and 20.0 ± 3.0 mU/ml 14 days after PTx. The reticulocyte count, however, increased significantly 2 weeks after PTx: from 25,103 ± 3,000 to 40,827 ± 4,080/mm³ (p < 0.01). In group III patients, serum iEPO, reticulocyte count, and hemoglobin remained stable after surgery. Since all group I patients had received vitamin D supplementation after PTx, we studied an additional group of 14 chronic dialysis patients (group IV) who received either calcitriol (1 μg/day, n = 7) or placebo (n = 7) during 14 days. The patients on calcitriol treatment, but not those on placebo, had a significant decrease of serum iEPO: 18.6 ± 4.9 versus 16.0 ± 4.2 mU/ml (p < 0.03). In conclusion, PTx led to a striking increase of serum iEPO and blood reticulocytes in uremic patients with secondary hyperparathyroidism, and an increase of reticulocyte count, but not of iEPO, in patients with primary hyperparathyroidism. Marked changes of circulating PTH, extra- or intracellular calcium and phosphorus concentrations as well as of tissue sensitivity to EPO after PTx could all be responsible. In contrast, the surgical procedure and the therapeutic increase in plasma calcitriol do not appear to be involved.