Effects of arginine supplementation on splenocyte cytokine mRNA expression in rats with gut-derived sepsis

AIM: To investigate the effects of arginine (Arg)-enriched diets before sepsis and/or Arg-containing total parenteral nutrition (TPN) after sepsis or both on cytokine mRNA expression levels in splenocytes of rats with gut-derived sepsis. METHODS: Rats were assigned to four experimental groups. Groups 1 and 2 were fed with a semipurified diet, while groups 3 and 4 had part of the casein replaced by Arg which provided 2% of the total calories. After the rats were fed with these diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP), at the same time an internal jugular vein was cannulated. All rats were maintained on TPN for 3 d. Groups 1 and 3 were infused with conventional TPN, while groups 2 and 4 were supplemented with Arg which provided 2% of the total calories in the TPN solution. All rats were killed 3 d after CLP to examine their splenocyte subpopulation distribution and cytokine expression levels. RESULTS: Plasma interleukin (IL)-2, IL-4, tumor necrosis factor-α(TNF-α) and interferon (IFN-γ) were not detectable 3 d after CLP. There were no differences in the distributions of CD45Ra+, CD3+, CD4+, and CD8+ cells in whole blood and splenocytes among the four groups. The splenocyte IL-2 mRNA expression in the Arg-supplemented groups was significantly higher than that in group 1. IL-4 mRNA expression in groups 3 and 4 was significantly higher than that in groups 1 and 2. The mRNA expression of IL-10 and IFN-γ was significantly higher in group 4 than in the other three groups. There was no difference in TNF-α mRNA expression among the four groups. CONCLUSION: The influence of Arg on the whole blood and splenic lymphocyte subpopulation distribution is not obvious. However, Arg administration, especially before and after CLP, significantly enhances the mRNA expression levels of Th1 and Th2 cytokines in the spleen of rats with gut-derived sepsis.     

Reversible cytotoxic edema in the splenium of the corpus callosum related to antiepileptic treatment: report of two cases and literature review

PURPOSE: Clinically silent lesions localized in the splenium of the corpus callosum (SCC) are a rare finding in the magnetic resonance imaging (MRI) of patients receiving antiepileptic drugs (AEDs). They are usually of benign character but may induce unnecessary complementary examinations if their nature is unrecognized. So far, 22 cases have been described in the literature, for which different etiologies have been proposed. We describe two further cases and discuss the probable lesion etiology. METHODS: We report two cases including a 25-year-old male patient and a 12-year-old female patient with a transient SCC lesion discovered in the context of a presurgical epilepsy evaluation. RESULTS: Comprehensive MRIs, including diffusion tensor imaging-based fiber tracking of the lesion, revealed a cytotoxic edema not disrupting neuronal fibers. Serum arginine vasopressin (AVP) measurements revealed an altered secretion during the acute phase in one patient. CONCLUSIONS: On the basis of our results, we hypothesize that the lesion consists of a cytotoxic edema, possibly induced by abrupt AED concentration changes and associated to alterations of AVP secretion.     

Inherited factor VII deficiency: identification of two novel mutations (A191V and T239P) in the catalytic domain

We describe here five F7 mutations found in four patients without bleeding history, despite constitutional coagulation Factor VII (FVII) deficiency. All five mutations are missense and affect the catalytic domain of FVII (A191T, A191V, T239P, R224Q and M298I). The A191V and T239P mutations are novel and were found in homozygous patients with no clinical bleeding tendency. The patient diagnosed with the A191V mutation had a phenotype corresponding to a moderate type 1 FVII deficiency (FVII:C 4%, FVII:Ag 5%). The T239P mutation was found in a patient with mild type 2 FVII deficiency (FVII:C 25%, FVII:Ag 95%). Novel mutations are both in close vicinity to the charge-stabilizing system of FVII. Modeling studies allow understanding in part the molecular basis for the loss of function.     

Full-thickness skin necrosis after arginine extravasation--a case report and review of literature

The arginine test is highly useful in the evaluation of short-stature children and adolescents. Extravasation of arginine can cause full-thickness skin necrosis that requires serious surgical intervention with aesthetic and functional sequellea. The authors describe a case of distal forearm skin necrosis caused by arginine extravasation that was treated by wide debridement and a combination of groin flap and later with split-thickness skin graft. The authors emphasize the need for early and active management of arginine extravasation injuries.     

Neurochemical correlates of male polymorphism and alternative reproductive tactics in the Azorean rock-pool blenny,Parablennius parvicornis

In the common Azorean rock-pool blenny, Parablennius parvicornis, males exhibit alternative reproductive morphologies: (1) larger males defend nest sites, provide parental care, have anal glands (involved in pheromone release), testicular glands, and low gonad:body weight ratio (GSI) and (2) smaller, younger, males do not defend nests, have reduced glands and high GSI. These smaller non-nesting males behave as satellites (associated with nests) or sneakers (moving among nests), attempting to achieve parasitic fertilizations via sperm competition. In non-mammals, arginine vasotocin (AVT) is a key hypothalamic peptide involved in the control of reproductive behavior and physiology, and several fish species that exhibit alternative male reproductive morphs show polymorphism in AVT brain chemistry. We conducted an immunocytochemical study to generate comparative data on this intertidal blenny. Our analysis showed no difference in AVT-immunoreactive cell number or size between the male morphs, which is consistent with studies on other fish, including blennies. The number of AVT cells was positively correlated to fish body mass, while cell size showed no such relation. If corrected for body mass, the smaller non-nesting males have significantly more cells than the large nesting males. Our data suggest that the size and number of forebrain AVT cells develops initially to allow for reproduction in the young non-nesting males and this pattern does not appear to change when males take on the nesting morphotype later in life. This result appears to be consistent in many fishes with alternative male morphotypes.     

Neurochemical phenotype of sympathetic nervous system outflow from brain to white fat

The sympathetic innervation of white adipose tissue (WAT) appears to be a dominant mechanism triggering lipolysis. The purpose of this study was to determine the neurochemical phenotype of neurons comprising the sympathetic outflow from brain to WAT. This was accomplished by injecting Siberian hamster WAT with a viral retrograde transneuronal tract tracer, the pseudorabies virus (PRV), in combination with immunocytochemical characterization of several neurotransmitters or their synthetic enzymes in the brain. Catecholaminergic (tyrosine hydroxylase [TH] and dopamine-beta-hydroxylase [DBH] immunoreactivity) and peptidergic (arginine vasopressin [AVP] and oxytocin [OXY] immunoreactivity) neurons were part of this outflow, but the percentage of double-labeled cells was small, consistent with previous studies. Brainstem PRV + TH- or PRV + DBH-labeled cells were in previously identified noradrenergic areas (A5, A6, and subcoeruleus, rostroventrolateral medulla [RVL], some reticular nuclei). Forebrain double labeling was greatest in the paraventricular (TH, AVP, OXY) and suprachiasmatic (AVP) nuclei, both implicated in the central control of lipolysis. Differences between the PRV double labeling reported here for WAT versus that of other sympathetic peripheral targets were PRV + DBH in A5 and RVL, and PRV + TH in RVL and in the lateral paragigantocellular and lateral reticular nuclei. Collectively, these results begin to identify the neurochemical identity of the sympathetic outflow from brain to WAT.     

肠外营养添加精氨酸与谷氨酰胺对胃癌患者术后免疫功能的影响

目的:评价联合应用精氨酸(arginine,Arg)和谷氨酰胺(glutamine,Glu)的肠外营养(parenteral nutri- tion,PN)对胃癌患者根治术后免疫功能影响。方法:将60例胃癌患者随机平分为四组:Arg组、Glu组、Arg+Glu组及常规PN组(Rou组)。术后第1天起各组均连续给予PN支持7d,均为等氮等热量。另取15例同期行择期手术的普外科腹部手术患者(其中胆囊息肉6例、胆囊结石9例)作为空白对照组。术前、术后第8天分别检测各组的细胞免疫和体液免疫指标。结果:术前60例胃癌患者的CD3、CD4、CD4/CD8、IgA、IgM及IgG均低于空白对照组(P<0.05),CD8则高于空白对照组(P<0.05)。术后第8天,IgA、IgM、IgG在Arg组、Glu组和Arg+Glu组三组之间差异无显著性,三组均高于Rou组(P<0.05);CD3、CD4的百分比及CD34/CD8比值在Arg组和Glu组组间差异无显著性,两组均高于Rou组(P<0.05),均低于Arg+Glu组(P<0.05);而CD8的百分比和CRP、C3、C4的浓度与上述相反,CD3、CD4及CD4/CD8在Arg+Glu组和Rou组组间差异有极为显著性(P<0.01)。结论:联合Arg和Glu增强的PN比单用Arg或Glu增强的PN更能增强胃癌患者根治术后细胞免疫功能。     

Prolactin response to arginine in children with hyperthyroidism and primary hypothyroidism

Plasma prolactin (PRL) response to arginine was examined in 16 prepubertal and 18 pubertal children with constitutional short stature, 5 patients with hyperthyroidism and 4 patients with primary hypothyroidism. The mean basal concentration of plasma PRL was significantly higher (P<0.01) in primary hypothyroidism than in other groups. Arginine infusion elicited significant (P<0.05) rises in plasma PRL in all groups. The maximal increment of plasma PRL above the baseline level after arginine stimulation was significantly larger (P<0.05) in pubertal than in prepubertal females and was significantly smaller (P<0.05) in patients with hyperthyroidism than in age- and sex-matched controls. There was no sex difference in arginine-stimulated PRL secretion. These data suggest that arginine produces a significant increase in plasma PRL and the PRL response to arginine was greater in pubertal than in prepubertal children. Plasma PRL response to arginine is suppressed in children with hyperthyroidism and the basal plasma PRL is markedly elevated in primary hypothyroidism.     

Neuroendocrine actions of organohalogens: Thyroid hormones, arginine vasopressin, and neuroplasticity

Organohalogen compounds are global environmental pollutants. They are highly persistent, bioaccumulative, and cause adverse effects in humans and wildlife. Because of the widespread use of these organohalogens in household items and consumer products, indoor contamination may be a significant source of human exposure, especially for children. One significant concern with regard to health effects associated with exposure to organohalogens is endocrine disruption. This review focuses on PCBs and PBDEs as old and new organohalogens, respectively, and their effects on two neuroendocrine systems; thyroid hormones and the arginine vasopressin system (AVP). Regarding neuroendocrine effects of organohalogens, there is considerable information on the thyroid system as a target and evidence is now accumulating that the AVP system and associated functions are also susceptible to disruption. AVP-mediated functions such as osmoregulation, cardiovascular function as well as social behavior, sexual function and learning/memory are discussed. For both thyroid and AVP systems, the timing of exposure seems to play a major role in the outcome of adverse effects. The mechanism of organohalogen action is well understood for the thyroid system. In comparison, this aspect is understudied in the AVP system but some similarities in neural processes, shown to be targeted by these pollutants, serve as promising possibilities for study. One challenge in understanding modes of action within neuroendocrine systems is their complexity stemming, in part, from interdependent levels of organization. Further, because of the interplay between neuroendocrine and neural functions and behavior, further investigation into organohalogen-mediated effects is warranted and may yield insights with wider scope. Indeed, the current literature provides scattered evidence regarding the role of organohalogen-induced neuroendocrine disruption in the neuroplasticity related to both learning functions and brain structure but future studies are needed to establish the role of endocrine disruption in nervous system function and development.     

Identification of two arginase isoenzyme activities along the nephron of Meriones shawi

 Conflicting theories on the existence of several renal arginase isoenzymes remain in debate. Because the activity of arginase is high in two embryologically different nephron segments of the Meriones shawi kidney, namely the cortical (CPST) and medullary (OSPST) proximal straight tubule and the outer medullary collecting duct (OMCD), we postulate that these nephron segments may contain different isoforms. Isolated nephron segments were dissected from collagenase-treated kidneys. Tubules were permeabilized with Triton X-100 (0.25%) and incubated with increasing Arg concentrations to characterize the arginase activity. The results were as follows: (1) in OMCD, one arginase isoform (E₁), characterized by a high Arg affinity (1.160 mM), was present; (2) in CPST, two arginase isoforms were discovered – one, E₁, had a similar K _m (1.407 mM) to that found in OMCD whereas the other (E₂) had a low affinity for Arg (K _m =18.8 mM); and (3) in OSPST, two isoenzymes were present – E₁ which had a K _m of 1.478 mM and the second isoform that we named E₂ which had a K _m of 9.07 mM. In addition, arginase located in CPST and OMCD was strongly inhibited by Orn and Lys. The K _i value for Lys varied between 1.635 and 2.288 mM. Therefore, this work demonstrates that two arginase isoforms are present in the kidney of Meriones shawi. Isoform E₁ is present in the proximal tubule and the collecting duct whereas isoform E₂ is restricted to the proximal tubule. Received: 13 August 1998 / Accepted: 25 September 1998