Synthesis of homoagmatine and GC–MS analysis of tissue homoagmatine and agmatine: evidence that homoagmatine but not agmatine is a metabolite of pharmacological L-homoarginine in the anesthetized rat

Amino Acids - Low L-homoarginine (hArg) concentrations in human blood and urine are associated with renal and cardiovascular morbidity and mortality, yet the underlying mechanisms and the...     

Personalized Medicine in Pediatrics: The Clinical Potential of Orodispersible Films

Children frequently receive medicines that are designed for adults. The dose of commercially available products is adapted, mostly based on the child’s bodyweight, thereby neglecting differences in pharmacokinetic and pharmacodynamics parameters. If commercial products are unsuitable for administration to children or are unavailable, extemporaneous pharmacy preparations are a good alternative. For this particular population, orodispersible films (ODFs) can be a highly attractive dosage form for the oral administration of drugs. ODFs are relatively easy to prepare in a hospital setting, create dose flexibility, and may suit an individual approach, especially for patients having difficulties in swallowing tablets or being fluid restricted. In this article, various aspects related to pharmacy preparations, clinical application, and preparation of ODFs for pediatric patients are highlighted and discussed.     

GC–MS measurement of spermidine and putrescine in serum of elderly subjects: intriguing association between spermidine and homoarginine

Amino Acids - Gas chromatography–mass spectrometry (GC–MS) methods were developed, validated and used to measure serum spermidine (SPD) and putrescine (PUT) in 9 seropositive...     

Humoral immunity in experimental syphilis: the demonstration of IgG as a treponemicidal factor in immune rabbit serum

The neutralizing activity present in immune rabbit serum (IRS) against virulent Treponema pallidum was shown to be mediated by IgG and complement. IgG was isolated and purified from both IRS and nonimmune rabbit serum (NRS) by the use of an affinity system in which staphylococcal protein A was conjugated to Sepharose 4B. The purity of the isolated IgG fractions was demonstrated by both immunoelectrophoresis and SDS-polyacrylamide gel electrophoresis. Fractions of IgG were tested for specific neutralizing activity as measured by an in vitro-in vivo neutralization test. Lesions failed to develop at 80% of the sites inoculated with treponemal suspensions containing IgG from IRS in the presence of unheated NRS as a source of complement; delayed atypical lesions were observed at the remaining sites. In contrast, typical lesions developed at all sites inoculated with suspensions containing IgG from IRS in the presence of heated NRS. They were significantly delayed, however, as compared with lesion development at control sites inoculated with suspensions containing IgG from NRS. These results provide the first direct evidence for an IgG complement-mediated treponemicidal mechanism operative in immune serum from rabbits with latent syphilis.     

Serum and cerebrospinal fluid concentrations of homoarginine,arginine, asymmetric and symmetric dimethylarginine,nitrite and nitrate in patients with multiple sclerosis and neuromyelitis optica

The pathogenic hallmarks of multiple sclerosis (MS) and neuromyelitis optica (NMO) are cellular and humoral inflammatory infiltrates and subsequent demyelination, or astrocytic cell death in NMO, respectively. These processes are accompanied by disruption of the blood–brain barrier as regularly observed by gadolinium enhancement on magnetic resonance imaging. The role of the l-arginine/nitric oxide (NO) pathway in the pathophysiology of neuroinflammatory diseases, such as MS and NMO, remains unclear. In the present study, we measured the concentrations of the nitric oxide (NO) metabolites nitrate and nitrite, the endogenous substrates of NO synthase (NOS) l-arginine (Arg) and l-homoarginine (hArg), and asymmetric dimethylarginine (ADMA), the endogenous inhibitor of NOS activity, in the serum and cerebrospinal fluid (CSF) of patients with MS, NMO or other neurologic diseases (OND). MS (551 ± 23 nM, P = 0.004) and NMO (608 ± 51 nM, P = 0.006) patients have higher ADMA concentrations in serum than healthy controls (HC; 430 ± 24 nM). For MS, this finding was confirmed in CSF (685 ± 100 nM in relapsing–remitting multiple sclerosis, RRMS; 597 ± 51 nM in secondary progressive multiple sclerosis, SPMS) compared with OND (514 ± 37 nM; P = 0.003). Serum concentrations of Arg (61.1 ± 9.7 vs. 63.6 ± 4.9 µM, P = 0.760), hArg (2.62 ± 0.26 vs. 2.52 ± 0.23 µM, P = 0.891), nitrate (38.1 ± 2.2 vs. 38.1 ± 3.0 µM) and nitrite (1.37 ± 0.09 vs. 1.55 ± 0.03 µM) did not differ between MS and OND. Also, CSF concentrations of hArg (0.685 ± 0.100 µM in RRMS, 0.597 ± 0.051 µM in SPMS, 0.514 ± 0.037 µM in OND), nitrate (11.3 ± 0.6 vs. 10.5 ± 0.3 µM) and nitrite (2.84 ± 0.32 vs. 2.41 ± 0.11 µM) did not differ between the groups. In NMO patients, however, serum Arg (117 ± 11 vs. 64 ± 4.9 μM, P = 0.004), nitrate (29 ± 2.1 vs. 38 ± 3 μM, P = 0.03), and nitrite (1.09 ± 0.02 vs. 1.55 ± 0.033 µM, P < 0.0001) were significantly different as compared to OND. Symmetric dimethylarginine (SDMA) concentration did not differ in serum between MS and HC (779 ± 43 vs. 755 ± 58 nM, P = 0.681) or in CSF between MS and OND patients (237 ± 11 vs. 230 ± 17 nM, P = 0.217). Our study suggests a potential role for ADMA and Arg in neuroinflammatory diseases with diverse functions in MS and NMO. Higher ADMA synthesis may explain reduced NO availability in NMO. hArg and SDMA seem not to play an important role in MS and NMO.