The vascular effects of different arginase inhibitors in rat isolated aorta and mesenteric arteries

Background and purpose

Arginase and nitric oxide (NO) synthase share the common substrate L-arginine, and arginase inhibition is proposed to increase NO production by increasing intracellular levels of L-arginine. Many different inhibitors are used, and here we have examined the effects of these inhibitors on vascular tissue.

Experimental approach

Each arginase inhibitor was assessed by its effects on isolated rings of aorta and mesenteric arteries from rats by: (i) their ability to preserve the tolerance to repeated applications of the endothelium-dependent agonist acetylcholine (ACh); and (ii) their direct vasorelaxant effect.

Key results

In both vessel types, tolerance (defined as a reduced response upon second application) to ACh was reversed with addition of L-arginine, (S)-(2-boronethyl)-L-cysteine HCl (BEC) or N^G-Hydroxy-L-arginine (L-NOHA). On the other hand, N^ω-hydroxy-nor-L-arginine (nor-NOHA) significantly augmented the response to ACh, an effect that was partially reversed with L-arginine. No effect on tolerance to ACh was observed with L-valine, nor-valine or D,L, α-difluoromethylornithine (DFMO). BEC, L-NOHA and nor-NOHA elicited endothelium-independent vasorelaxation in both endothelium intact and denuded aorta while L-valine, DFMO and nor-valine did not.

Conclusions and implications

BEC and L-NOHA, but not nor-NOHA, L-valine, DFMO or nor-valine, significantly reversed tolerance to ACh possibly conserving L-arginine levels and therefore increasing NO bioavailability. However, both BEC and L-NOHA caused endothelium-independent vasorelaxation in rat aorta, suggesting that these inhibitors have a role beyond arginase inhibition alone. Our data thus questions the interpretation of many studies using these antagonists as specific arginase inhibitors in the vasculature, without verification with other methods.     

Electroencephalographic cerebral dysrhythmic abnormalities in the trinity of nonepileptic general population, neuropsychiatric, and neurobehavioral disorders

Subclinical electroencephalographic epileptiform discharges in neurobehavioral disorders are not uncommon. The clinical significance and behavioral, diagnostic, and therapeutic implications of this EEG cerebral dysrhythmia have not been fully examined. Currently the only connotation for distinctive epileptiform electroencephalographic patterns is epileptic seizures. Given the prevailing dogma of not treating EEGs, these potential aberrations are either disregarded as irrelevant or are misattributed to indicate epilepsy. This article reappraises the literature on paroxysmal EEG dysrhythmia in normative studies of the "healthy" nonepileptic general populations, neuropsychiatry, and in neurobehavioral disorders. These EEG aberrations may be reflective of underlying morpho-functional brain abnormalities that underpin various neurobehavioral disturbances.     

Sensory gating in the human hippocampal and rhinal regions: regional differences

To further explore the roles of medial temporal structures in mediating sensory gating of incoming irrelevant or redundant auditory input, twenty-seven patients with intractable epilepsy with depth electrodes implanted in the medial temporal lobe for presurgery evaluation underwent evoked response recording to auditory paired-stimuli (S1-S2). Seventeen subjects were diagnosed with left medial temporal lobe epilepsy (MTLE) and 10 with right MTLE. Only data from the nonlesion side were included. Twenty-three records from rhinal and anterior hippocampal regions, and 21 from posterior hippocampal regions were included in the analysis. The rhinal region had two prominent components (a negativity peaking around 200 ms followed by a positivity peaking around 400 ms). Both the anterior and posterior hippocampal regions exhibited a dominant negative potential peaking around 400 ms. These components were all composed predominantly of slower frequencies. In contrast, a negativity in the posterior hippocampus at around 100 ms was composed of slow and fast frequencies. All components but the early rhinal negativity were attenuated by stimulus repetition. This is the first report documenting that different regions of the medial temporal area are differentially involved in the processing of auditory input, most likely reflecting separate steps of processing. The data support the need for further exploration of the contribution of these regions to sensory gating. This information helps to increase our understanding of this basic but important and complex function.     

Attentional deficits in cocaine-dependent patients: converging behavioral and electrophysiological evidence

Although there are several reports of patients with cocaine dependence displaying cognitive deficits, the nature of their information processing deficits is not well characterized. In the present study, the attentional performance of cocaine-dependent patients (n=14) was examined and compared with that of healthy control individuals (n=15). Attention was assessed using an auditory oddball event-related task as well as the Continuous Performance Test (CPT, Identical Pairs version). The cocaine-dependent group displayed P300 amplitude reduction compared to controls. The group difference in P300 response latency did not reach significance. On the CPT, the cocaine-dependent patients displayed significantly poorer discriminability and greater errors of commission than the controls. There was a positive correlation between performance on the oddball event-related task and performance on the CPT. This investigation provides converging behavioral and electrophysiological evidence of attentional deficits in cocaine-dependent patients.     

CDC25 phosphatases in cancer cells: key players? Good targets?

Cell division cycle 25 (CDC25) phosphatases regulate key transitions between cell cycle phases during normal cell division, and in the event of DNA damage they are key targets of the checkpoint machinery that ensures genetic stability. Taking only this into consideration, it is not surprising that CDC25 overexpression has been reported in a significant number of human cancers. However, in light of the significant body of evidence detailing the stringent complexity with which CDC25 activities are regulated, the significance of CDC25 overexpression in a subset of cancers and its association with poor prognosis are proving difficult to assess. We will focus on the roles of CDC25 phosphatases in both normal and abnormal cell proliferation, provide a critical assessment of the current data on CDC25 overexpression in cancer, and discuss both current and future therapeutic strategies for targeting CDC25 activity in cancer treatment.     

Low Common Bile Duct Bifurcation Incidentally Discovered During Pancreaticoduodenectomy

Introduction  

Bile duct injury due to failure to recognize anatomical variations can have considerable consequences.     

Open Cystogastrostomy,Retroperitoneal Drainage,and G-J Enteral Tube for Complex Pancreatitis-Associated Pseudocyst: 19 Patients with no Recurrence

Introduction  

Various techniques have been described to achieve definitive resolution of complex acute pancreatitis associated pseudocysts (PACs). Many of these strategies, inclusive of open, minimally invasive, and radiological procedures, are hampered by high recurrence or failed resolution, particularly for PAC near the pancreatic head. The present series describes a multimodal strategy combining a minilaparotomy for anterior gastrostomy for the creation of a stapled posterior cystogastrostomy, placement of an 8F secured silastic tube for intentional formation of a cystogastric fistula tract in combination with gastric drainage, and postduodenal enteral alimentation.     

Transfer of flexor carpi ulnaris branch of the ulnar nerve to the pronator teres nerve: histomorphometric analysis

Partial median-nerve injury high in the upper extremity, resulting from brachial plexus neuritis or trauma, can affect the pronator teres muscle and result in the inability to pronate the forearm. A nerve transfer from an ulnar nerve-innervated branch to the flexor carpi ulnaris (FCU) muscle to the branch to the pronator teres (PT) is an attractive option in this clinical scenario. This study, a histomorphometric analysis of nine cadaver specimens harvested at the proposed FCU branch to PT branch transfer site, demonstrates sufficient similarities between the two branches in total number of nerve fibers (371.6 with SEM 35.1, and 361.9 with SEM 47.1; p = 0.87) and nerve cross-sectional area (122,181 microm2 with SEM 14,546 microm2, and 142,492 microm2 with SEM 19,633 microm2; p = 0.42), to predict a functional transfer result. In addition, clinical application of this transfer resulted in functional pronation strength of M4+.