老年人急性颅脑损伤早期血浆精氨酸加压素含量变化的研究

目的研究老年人急性颅脑损伤早期血浆中精氨酸加压素（AVP）的变化及临床意义。方法用放射免疫（RIA）法检测32例老年人急性颅脑损伤早期患者,30例非颅脑损伤早期患者和30例健康老年人的血浆AVP,分析和观察其临床变化。结果32例老年人急性颅脑损伤早期组血浆AVP［（48．30±8．28）ng／人］明显高于非颅脑损伤早期组［（25．56±4．64）ng／L］,P＜0.01;非颅脑损伤早期组高于老年健康组［（5.06±4.12）ng／L］,P＜0．01。其中老年人急性颅脑损伤早期组中GCS评分与AVP呈负性相关,P＜0.01;而非颅脑损伤的早期组与GCS评分无明显意义,P＞0．05。结论AVP参与了各种急性损伤早期的病理生理过程,但急性颅脑损伤早期组明显高于非颅脑损伤早期组,尤其颅脑损伤早期组中GCS评分＞8分明显高于＜8分组,颅脑损伤越严重,AVP越高,提示AVP可作为观察老年人,颅脑损伤早期严重程度的标志之一,对临床抢救具有指导意义。     

Arginine vasopressin as a target in the treatment of acute heart failure

Congestive heart failure (CHF) is one of the most common reasons for hospitalization in the United States. Despite multiple different beneficial medications for the treatment of chronic CHF, there are no therapies with a demonstrated mortality benefit in the treatment of acute decompensated heart failure. In fact, studies of inotropes used in this setting have demonstrated more harm than good. Arginine vasopressin has been shown to be up regulated in CHF. When bound to the V1a and/or V2 receptors, vasopressin causes vasoconstriction, left ventricular remodeling and free water reabsorption. Recently, two drugs have been approved for use that antagonize these receptors. Studies thus far have indicated that these medications, while effective at aquaresis (free water removal), are safe and not associated with increased morbidity such as renal failure and arrhythmias. Both conivaptan and tolvaptan have been approved for the treatment of euvolemic and hypervolemic hyponatremia. We review the results of these studies in patients with heart failure.     

Urinary ET-1, AVP and sodium in premature infants treated with indomethacin and ibuprofen for patent ductus arteriosus

The relative potency and interrelationship between vasoactive and natriuretic mediators are thought to be important in the transition from fetal to neonatal life. The relationship between urinary vasoactive factors and sodium excretion has not been adequately addressed in premature infants receiving indomethacin and ibuprofen for therapy of patent ductus arteriosus. Excretion rates of AVP, ET-1 and sodium were measured in premature infants with RDS receiving indomethacin or ibuprofen. Forty-four RDS premature infants (<34-week gestation) with PDA received either ibuprofen (n=22) in an initial dose of 10 mg/kg followed by two doses of 5 mg/kg each after 24 and 48 h or 3 doses at 12-h intervals of indomethacin (n=24), 0.2 mg/kg, infused continuously over a period of 15 min. Urinary ET-1, AVP and sodium excretion were measured before and after treatment. Indomethacin treatment caused a significant decrease in urinary ET-1 and AVP excretion (UET-1/Ucr 0.14±0.01 vs. 0.10±0.05 fenton/mmol; P<0.05; 24.42±6.18 vs. 12.63±3.06 pg/mmol; P<0.05, respectively), along with a significant reduction in urinary sodium (92.1±36.1 vs. 64.8±35.6 mmol/l; P<0.01), fractional excretion of sodium (6.8±37.1 vs. 4.5±37.1%; P<0.01) and urinary osmolality (276.2±103.9 vs. 226.4±60.3 mOsmol/kg; P<0.05). Ibuprofen treatment caused a significant decrease in urinary AVP (UAVP/Ucr 24.5±3.4 vs. 16.3±2.04 pg/mmol; P<0.01), along with a significant decrease in urinary sodium (78.0±8.4 vs. 57.0±8.0 mmol/l; P<0.05) and in fractional excretion of sodium (7.5±1.3 vs. 3.9±3.0%; P<0.05), while it did not modify urinary ET-1 excretion. The association of renal ET-1 and AVP activity with sodium excretion in premature infants treated with indomethacin and ibuprofen supports the hypothesis that these factors may play a role in the physiologic changes in sodium excretion.     

Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree

Arginine:glycine amidinotransferase (AGAT, EC 2.1.4.1) deficiency is a recently recognized autosomal recessive inborn error of creatine biosynthesis, characterized by mental retardation and severe language impairment. We extensively investigated a third 5-year-old patient with AGAT deficiency, discovered in the pedigree of the same Italian family as the two index cases. At the age of 2 years he presented with psychomotor and language delay, and autistic-like behavior. Brain MRI was normal, but brain 1H-MRS disclosed brain creatine depletion, which almost completely normalized following creatine monohydrate supplementation. A remarkable clinical improvement paralleled the restoration of brain creatine concentration. AGAT and GAMT (guanidinoacetate:methyltransferase) genes were analyzed in the proband and in 26 relatives, including the two cousins with AGAT deficiency. Sequencing of the proband's AGAT gene disclosed the same homozygous mutation at nt position 9093 converting a tryptophan (TGG) to a stop codon (TAG) at residue 149 (W149X), as already described in the two previously reported cases. The proband's parents and 10 additional subjects of the pedigree were carriers for this mutation. AGAT deficiency was further confirmed by undetectable AGAT activity in the patient's lymphoblasts. Mutation analysis of the GAMT gene revealed a sequence variation in exon 6 (T209M), not in the proband, but in 15 additional subjects from the pedigree. The silent nature of this sequence variation is supported by its homozygosity in one AGAT deficient cousin and in one asymptomatic adult, both with normal GAMT activity.     

Arginine vasopressin release inhibitor RU51599 attenuates brian oedema following transient forebrain ischaemia in rats

Summary RU51599 is an arginine vasopressin (AVP) release inhibitor and a selective kappa opioid agonist which has a pure water diuresis effect without associated electrolyte excretion. The effect of RU51599 on brain oedema following transient forebrain ischaemia in rats was examined. Under microscopy, the visible vertebral arteries at the second vertebra could be easily electrocauterized and completely cut by microscissors to yield complete cessation of circulation of both vertebral arteries. Transient forebrain ischaemia was induced by this improved highly reproducible technique of four-vessel occlusion model. Forty-three male Wistar rats were separated into six groups; saline-treated (1 ml/kg) normal rats (n=10), RU51599-treated (1 mg/kg) normal rats (n=4), saline-treated (1 ml/kg) rats with complete occlusion of both vertebral arteries (n=5), RU51599-treated (1 mg/kg) rats with complete occlusion of both vertebral arteries (n=5), saline-treated (1 ml/kg) rats with both complete occlusion of both vertebral arteries and carotid occlusion bilaterally during 45 minutes followed by 60 minutes of reperfusion (n=11), RU51599-treated (1 mg/kg) rats with both complete occlusion of both vertebral arteries and carotid occlusion bilaterally during 45 minutes followed by 60 minutes of reperfusion (n=8). The brain water content was determined by the dry-wet weight method. Cerebral blood flow was monitored during ischaemia and reperfusion was performed by laser Doppler flowmetry to make sure to obtain reversible forebrain ischaemia. Effects of RU51599 on concentration of glutamate released from the hippocampal CA1 of rats subjected to 5 minutes four-vessel occlusion and 60 minutes of reperfusion were also investigated by the microdialysis method. This modified four-vessel occlusion method produced reversible forebrain ischaemia with a high level of success. Bilateral carotid occlusion followed by 60 minutes reperfusion caused a significant increase in brain water content (P<0.01), which was significantly attenuated by RU51599 (P<0.01). These findings indicate that the AVP-release inhibitor RU51599 reduced brain oedema following transient forebrain ischaemia in rats.     

Renal transport of lysine and arginine in lysinuric protein intolerance

In a patient with lysinuric protein intolerance, renal handling of lysine and arginine was examined to study the renal transport mechanism of this disease. The tubular reabsorption of lysine or arginine of the patient, when the filtered load of amino acid was increased by intravenous infusion, was not raised as much as that of control subjects at low filtered loads, but the ability for amino acid reabsorption seemed to exist under these conditions. However, when the filtered load was greatly increased, instead of a net reabsorption, a net secretion of amino acid was obtained. This seems to mean that at low filtered loads the amino acid in the tubular lumen is accumulated by the tubular cell across the intact luminal membrane, leading to a small amino acid excretion in the urine. With a great increase of the filtered load the saturated intracellular amino acid, which is not transported to the capillary because of a transport defect of the basolateral membrane, is assumed to leak back into the lumen. This causes a marked urinary amino acid loss exceeding filtered load at high tubular loads.The intravenous load of lysine depressed the percentage of arginine reabsorption and arginine load depressed lysine reabsorption. The percentage of the depressed amino acid reabsorption of the patient decreased almost linearly with increases of the inhibitor load.     

Predominant localization in glial cells of freel-arginine. Immunocytochemical evidence

Nitric oxide has been recently identified as an endogenous activator of the soluble guanylate cyclase in the brain as well as in vascular endothelial cells and macrophages. In the present study, we determined the localization of free arginine in the brain because nitric oxide was formed from the terminal guanido group ofl-arginine. Anti-arginine antiserum was raised in guinea pigs by repeated injection ofl-arginine covalently conjugated to guinea pig serum albumin via glutaraldehyde. Specicic anti-arginine antibody was purified from the antiserum by using an affinity gel coupled withl-arginine. Arginine-like immunoreactivity in the rat brain and spinal cord was found concentrated mainly in astrocytes including Bergmann glial cells in the cerebellum and processes of astrocytes around blood vessels. The present results suggest that glial cells, particularly astrocytes, are the main locus ofl-arginine, a nitric oxide precursor, in the brain.