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Rivers are increasingly being subjected to increased anthropogenic pollution stresses that are undermining their designated-uses and negatively affecting sensitive coastal areas. In this study, the water quality of the Beirut River, a poorly monitored seasonal Mediterranean River, is quantified. Water quality samples were collected on a regular basis over two consecutive years (2016 and 2017) from four sampling sites that represent a gradient of increased urbanization. The spatio-temporal variability of the physio-chemical (pH, Total Suspended Sediment (TSS), Nitrates-nitrites (NOx), sulfates (SO4-2), Total Phosphorus (TP), Total Nitrogen (TN), temperature, conductivity, chemical oxygen demand (COD) and bio-chemical oxygen demand (BOD)) and biological (fecal coliform and total coliform) pollution levels were statistically analysed in an effort to better understand the contribution of point and non-point pollution sources. The results showed significant yearly as well as seasonal variability and a high correlation between the measured pollution levels and river flow levels. Spatially, pollution levels appeared to correlate well with the urbanization levels in the basin. Future work will focus on modeling and further characterizing the pollutant loads reaching the Beirut River Basin. It is hoped that this study will give decision makers a better understanding of the water quality in the Beirut River and thus facilitate the development of an integrated comprehensive and transparent river basin management plan.

BACKGROUND & AIMS: Glutamine and vitamin E may prevent hepatic ischemia-reperfusion (I/R) injuries. Our aim was to investigate the effects of glutamine, either alone or combined with vitamin E, against I/R in the isolated perfused rat liver. METHODS: Four groups of 8 livers from male Sprague-Dawley rats were isolated and submitted to a 45-min no-flow ischemia and reperfusion in the presence of alanine 2 mM, alanine 2 mM plus vitamin E 150 microM, Alanyl-Glutamine (AlaGln) 2 mM, or AlaGln 2 mM plus vitamin E 150 microM. Six non-perfused livers were studied in parallel. Liver function, metabolic parameters, oxidative stress and inflammatory parameters have been studied. RESULTS: AlaGln was rapidly cleared from the perfusate (436+/-41 nmol min(-1) g(-1)) and lowered transaminase release during reperfusion (ALT: -59%), significantly so in the AlaGln+Vit E group (ALT: -65%, p<0.05). The association of glutamine with vitamin E led to lower degrees NO (-83%, p<0.05) production, better preserved hepatic glutathione content and, as with vitamin E alone, preserved hepatic vitamin A and significantly decreased malondialdehyde (-85%, p<0.05). CONCLUSION: Both glutamine, by attenuating inflammatory response, and vitamin E, via its antioxidative properties, showed complementary protective effects against I/R-induced hepatic injury. These data emphasize the potential benefit of combining glutamine and vitamin E supplementation in hepatic I/R injury. [ABSTRACT FROM AUTHOR]

(1) A 24 h urinary free cortisol (UFF) is one of the first-line exams recommended for the diagnosis of Cushing's syndrome. In a hospital hormonology department, this activity can exceed several hundred dosages per week. The UFF is generally determined via an immunoassay with an automate using a chemiluminescence or electrochemiluminescence detection system. To increase the cortisol concentration in the analyzed sample, the automated analysis is preceded by urine extraction, which does not prevent there from being some interferences due to other steroids with close structures. (2) This paper describes the development of on-line solid phase extraction coupled to liquid chromatography and mass spectrometry for the analysis of urinary free cortisol. The on-line extraction was based on the Turboflow TM chromatography coupled to the analytical column by two valves, easily available for the laboratories. (3) The choice of the Accucore Polar Premium ® analytical column made it possible to avoid analytical interferences with exogenous or endogenous molecules having the same SRM transition (363 → 121) as cortisol. (4) The method was fully validated in the range of clinically relevant concentrations from the lower limit of quantification (LLOQ) to 411.75 nmol·L -1 .

Endothelial cells (ECs) are constantly submitted in vivo to hemodynamical forces derived from the blood circulation, including shear stress (SS). ECs are able to detect SS and consequently adapt their phenotype, thus affecting many endothelial functions. If a plethora of shear stress-regulated molecular networks have been described in peripheral ECs, less is known about the molecular responses of microvascular brain ECs which constitute the blood-brain barrier (BBB). In this work, we investigated the response of human cerebral microvascular ECs to laminar physiological shear stress using the well characterized hCMEC/D3 cell line. Interestingly, we showed that hCMEC/D3 cells responded to shear stress by aligning perpendicularly to the flow direction, contrary to peripheral endothelial cells which aligned in the flow direction. Whole proteomic profiles were compared between hCMEC/D3 cells cultured either in static condition or under 5 or 10 dyn.cm -2 SS for 3 days. 3592 proteins were identified and expression levels were significantly affected for 3% of them upon both SS conditions. Pathway analyses were performed which revealed that most proteins overexpressed by SS refer to the antioxidant defense, probably mediated by activation of the NRF2 transcriptional factor. Regarding down-regulated proteins, most of them participate to the pro-inflammatory response, cell motility and proliferation. These findings confirm the induction of EC quiescence by laminar physiological SS and reveal a strong protective effect of SS on hCMEC/D3 cells, suggesting a similar effect on the BBB. Our results also showed that SS did not significantly increase expression levels nor did it affect the localization of junctional proteins and did not afect either the functional activity of several ABC transporters (P-glycoprotein and MRPs). This work provides new insights on the response of microvascular brain ECs to SS and on the importance of SS for optimizing in vitro BBB models., (© 2022. The Author(s).)

In the MITICA (Mother-to-Infant TransmIssion of microbiota in Central-Africa) study, 48 mothers and their 50 infants were followed from delivery to 6 months between December 2017 and June 2019 in Bangui (Central-African Republic). Blood tests and stool analyses were performed in mothers at delivery, and their offspring at birth, 11 weeks and 25 weeks. Stool cultures were performed in specific growth media for Salmonella, Shigella, E. coli, Campylobacter, Enerobacter, Vibrio cholerae, Citrobacter and Klebsiella, as well as rotavirus, yeasts and parasitological exams. The median vitamin C levels in mothers at delivery were 15.3 μmol/L (inter-quartile-range [IQR] 6.2-27.8 μmol/L). In infants, the median vitamin C levels at birth were 35.2 μmol/L (IQR 16.5-63.9 μmol/L). At 11 and 25 weeks, the median vitamin C levels were 41.5 μmol/L (IQR 18.7-71.6 μmol/L) and 18.2 μmol/L (IQR 2.3-46.6 μmol/L), respectively. Hypovitaminosis C was defined as seric vitamin C levels <28 μmol/L and vitamin C deficiency was defined as vitamin C levels <11 μmol/L according to the WHO definition. In mothers, the prevalence of hypovitaminosis-C and vitamin C deficiency at delivery was 34/45 (75.6%) and 19/45 (42.2%), respectively. In infants, the prevalence of hypovitaminosis-C and vitamin C deficiency at 6 months was 18/33 (54.6%) and 11/33 (33.3%), respectively. Vitamin C levels in mothers and infants were correlated at birth (Spearman's rho = 0.5; P value = 0.002), and infants had significantly higher levels of vitamin C (median = 35.2 μmol/L; IQR 16.5-63.9 μmol/L), compared to mothers (median = 15.3 μmol/L; IQR 6.2-27.8 μmol/L; P value <0.001). The offspring of vitamin C-deficient mothers had significantly lower vitamin C levels at delivery (median = 18.7 μmol/L; IQR 13.3-30.7 μmol/L), compared to the offspring of non-deficient mothers (median = 62.2 μmol/L; IQR 34.6-89.2 μmol/L; P value <0.001). Infants with hypovitaminosis-C were at significantly higher risk of having a positive stool culture during the first 6 months of life (adjusted OR = 5.3, 95% CI 1.1; 26.1; P value = 0.038)., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Rivers are increasingly being subjected to increased anthropogenic pollution stresses that undermine their designated uses and negatively affect sensitive coastal regions. The degradation of river water quality is attributed to both point and nonpoint sources of pollution. In this study, we determine the relative contribution of point and nonpoint pollutant loads in the Beirut River basin, a poorly monitored seasonal Mediterranean river. Water quality samples were collected on a weekly basis over 2 consecutive years (2016 and 2017) from four sampling sites that represent a gradient of increasing urbanization. Flow-concentration models were first developed to estimate total phosphorus (TP), total nitrogen (TN), and total suspended solids (TSS) loads reaching the different sub-basins. The performance of the regression models varied by location and by pollutant, with improved performance in the downstream sections (adjusted R 2 66% for TP and 59% for TN). Loads were also determined using the Beale's ratio method, which generally underestimated the loads as compared with the regression-based models. The relative contribution of the nonpoint source loads were then quantified using the Open Nonpoint Source Pollution and Erosion Comparison Tool (OpenNSPECT). The results showed that point sources were the main cause of water quality impairment across the entire basin, with load contributions varying between 75% in the headwaters and 98% in the urbanized downstream sections. The adopted modeling approach in this study provides an opportunity to better understand pollutant load dynamics in poorly monitored basins and a mechanism to apportion pollution loads between point and nonpoint sources.

N -carbamoyl putrescine (NCP), the decarboxylation derivative of citrulline, metabolically related to polyamines, may exert biological effects in mammals. The aim of this study was (i) to evaluate the nutritional properties of NCP in healthy rats and (ii) to determine the effect of NCP administration on muscle metabolism in malnourished old rats. The nutritional properties of NCP were first evaluated in 20 8-week-old male rats randomized to receive for two weeks a standard diet either alone (C group) or supplemented with NCP, 5 or 50 mg/kg/d. In a second study, 29 malnourished 18-month-old male rats were studied either before or after a 4-day refeeding with a standard diet either alone (REN group) or supplemented with NCP, 1 or 10 mg/kg/d. NCP had no effect on weight gain and body composition in either of the two studies. In healthy rats, muscle protein content was significantly increased in the soleus with NCP 5 mg/kg/d. A decrease in plasma glutamine and kidney spermine was observed at the 50 mg/kg/d dose; otherwise, no significant changes in plasma chemistry and tissue polyamines were observed. In malnutrition-induced sarcopenic old rats, refeeding with NCP 10 mg/kg/d was associated with higher tibialis weight and a trend for increased protein content in extensor digitorum longus (EDL). While the muscle protein synthesis rate was similar between groups, ribosomal protein S6 kinase was increased in tibialis and higher in the EDL in NCP-treated rats. The muscle RING-finger protein-1 expression was decreased in tibialis and urinary 3-methyl-histidine to creatinine ratio slightly lower with the supply of NCP. However, this initial period of refeeding was also associated with elevated fasted plasma triglycerides and glucose, significant in NCP groups, suggesting glucose intolerance and possibly insulin resistance. NCP was well-tolerated in healthy young-adults and in malnourished old rats. In healthy adults, NCP at 5 mg/kg/d induced a significant increase in protein content in the soleus, a type I fiber-rich muscle. In malnourished old rats, NCP supply during refeeding, may help to preserve lean mass by limiting protein breakdown; however, these effects may be limited in our model by a possible immediate refeeding-associated glucose intolerance.

Aims: Altered pancreatic exocrine function can be observed in patients with type 1 or type 2 diabetes. In the present study, we evaluated the potential nutritional consequences of this dysfunction., Methods: Serum concentrations of nutritional markers, including albumin, cholesterol, triacylglycerol, vitamins A, D, and E, were assessed in a cohort of 468 patients (137 with type 1 diabetes and 331 with type 2 diabetes), after exclusion of the patients with a CRP > 10 mg/l. These patients were compared with 47 patients with diseases of the exocrine pancreas and diabetes (type 3c diabetes or pancreatogenic diabetes). Fecal elastase-1 and chymotrypsin concentrations were measured and patients with type 1 and type 2 diabetes were divided into three groups according to whether zero (group NN), one (group LN), or both (group LL) concentrations were decreased., Results: Several markers differed significantly between the groups of patients, including BMI, albumin, phosphorus, and fat-soluble vitamins. Patients with pancreatogenic diabetes had markedly more profound alterations than patients with type 1 or type 2 diabetes and altered exocrine function. However, patients with type 1 or type 2 diabetes and decreased concentrations of both elastase-1 and chymotrypsin had lower albumin, phosphorus, and vitamin A than patients with normal pancreatic exocrine function., Conclusions: Modest nutritional alterations were found in patients with type 1 or type 2 diabetes and altered exocrine function. Patients with type 1 or type 2 diabetes and altered exocrine function may thus deserve to be screened for nutritional deficiencies.

Objective: In critically ill patients, acute injury alters gut function, causing greater risk for sepsis and malnutrition. Peptide-enriched diets may promote nitrogen absorption, whereas ω3-enriched diets reduce alterations in gut barrier function. The aim of this study was to assess the effectiveness of a peptide- and ω3-enriched diet on the metabolic response to injury and the gut barrier function in a model of prolonged catabolism in the rat. Given the intestinal trophic effect of glutamine, we tested for a synergistic effect of glutamine., Methods: We randomized 40 male Sprague-Dawley rats (250 g) into four groups to enterally receive a standard high-protein diet (S), or a peptide- and ω3-enriched diet either alone (IMN) or supplemented with glutamine and alanine supplied as dipeptide (DIP) or as free amino acids (AAs) for 4 d. Metabolic response to injury was induced by turpentine injections on days 1 and 3. At sacrifice, nutritional and inflammatory biomarkers and intestinal and liver function were assessed., Results: Weight gain (+45-62%) and nitrogen balance (+33-56%) were significantly higher in all groups than in the S group. In jejunal mucosa, total glutathione was significantly higher (+20-30%) and myeloperoxidase activity significantly lower in all groups compared with the S group. Hepatic triacylglycerol content was significantly lower in the AA (0.30 ± 0.04 μM/g) and DIP (0.43 ± 0.08 μM/g) groups than in the S group (0.71 ± 0.08 μM/g)., Conclusions: In this model of prolonged catabolism, compared with a standard diet, a peptide- and ω3-enriched diet improved metabolic response to injury, with better nitrogen balance and weight recovery, and decreased intestinal myeloperoxidase activity. Only marginal additional effects of glutamine supplementation were observed with decreased hepatic fat content., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Steatosis can sensitise the liver to various challenges and favour the development of non-alcoholic fatty liver disease (NAFLD). In this context, fructose feeding promotes endotoxin translocation from the gut, contributing to disease progression via an inflammatory process. Citrulline is protective against fructose-induced NAFLD; we hypothesised that this property might be related to its anti-inflammatory and antioxidative action against endotoxin-induced hepatic injuries. This hypothesis was evaluated in a model of perfused liver isolated from NAFLD rats. Male Sprague-Dawley rats (n 30) were fed either a standard rodent chow or a 60 % fructose diet alone, or supplemented with citrulline (1 g/kg per d) for 4 weeks. After an evaluation of their metabolic status, fasted rats received an intraperitoneal injection of lipopolysaccharide (LPS) (2·5 mg/kg). After 1 h, the livers were isolated and perfused for 1 h to study liver function and metabolism, inflammation and oxidative status. In vivo, citrulline significantly decreased dyslipidaemia induced by a high-fructose diet and insulin resistance. In the isolated perfused rat livers, endotoxaemia resulted in higher cytolysis (alanine aminotransferase release) and higher inflammation (Toll-like receptor 4) in livers of fructose-fed rats, and it was prevented by citrulline supplementation. Oxidative stress and antioxidative defences were similar in all three groups. Amino acid exchanges and metabolism (ammonia and urea release) were only slightly different between the three groups. In this context of mild steatosis, our results suggest that fructose-induced NAFLD leads to an increased hepatic sensitivity to LPS-induced inflammation. Citrulline-induced restriction of the inflammatory process may thus contribute to the prevention of NAFLD.

Context: Neuroendocrine and immune stresses imposed by chronic sleep restriction are known to be involved in the harmful cardiovascular effects associated with poor sleep., Objectives: Despite a well-known beneficial effect of napping on alertness, its effects on neuroendocrine stress and immune responses after sleep restriction are largely unknown., Design: This study was a strictly controlled (sleep-wake status, light environment, caloric intake), crossover, randomized design in continuously polysomnography-monitored subjects., Setting: The study was conducted in a laboratory-based study., Participants: The subjects were 11 healthy young men., Intervention: We investigated the effects on neuroendocrine and immune biomarkers of a night of sleep restricted to 2 h followed by a day without naps or with 30 minute morning and afternoon naps, both conditions followed by an ad libitum recovery night starting at 20:00., Main Outcome Measures: Salivary interleukin-6 and urinary catecholamines were assessed throughout the daytime study periods., Results: The increase in norepinephrine values seen at the end of the afternoon after the sleep-restricted night was not present when the subjects had the opportunity to take naps. Interleukin-6 changes observed after sleep deprivation were also normalized after napping. During the recovery day in the no-nap condition, there were increased levels of afternoon epinephrine and dopamine, which was not the case in the nap condition. A recovery night after napping was associated with a reduced amount of slow-wave sleep compared to after the no-nap condition., Conclusions: Our data suggest that napping has stress-releasing and immune effects. Napping could be easily applied in real settings as a countermeasure to the detrimental health consequences of sleep debt.

Objective: Periodontal disease has been associated with systemic inflammation and may be a risk factor for autoimmune diseases. This study evaluated the association between periodontal disease and the risk of incident psoriasis in a large prospective cohort study., Material and Methods: Self-reported history of periodontal bone loss, from 1998-2008, was evaluated as a risk factor for incident psoriasis among 60,457 women in the Nurses' Health Study. Secondary analyses examined associations between history of tooth loss and number of natural teeth and psoriasis risk. Cox proportional hazards models were used to assess multivariate estimates, adjusting for age, cigarette smoking, body mass index, alcohol intake and physical activity., Results: An increased multivariate risk of psoriasis was observed for those with mild periodontal bone loss (RR = 1.35, 95% CI = 1.03-1.75) and moderate-to-severe periodontal bone loss (RR = 1.49, 95% CI = 1.08-2.05), as compared to those without periodontal bone loss, after adjusting for age, cigarette smoking, body mass index, alcohol intake, physical activity and tooth loss. Number of natural teeth and tooth loss were not associated with risk of psoriasis in this study., Conclusion: This study shows that a history of periodontal bone loss may increase risk of subsequent psoriasis. A limitation of this study is that it is based on self-reported measures.

In the organism, quiescent epithelial cells have the potential to resume cycling as a result of various stimuli, including wound healing or oxidative stress. Because quiescent cells have a low polyamine level, resuming their growth requires an increase of their intracellular polyamine levels via de novo polyamine synthesis or their uptake from plasma. Another alternative, explored here, is an intercellular exchange with polyamine-rich cycling cells via gap junctions. We show that polyamines promote gap junction communication between proliferating cells by promoting dynamical microtubule plus ends at the cell periphery and thus allow polyamine exchange between cells. In this way, cycling cells favor regrowth in adjacent cells deprived of polyamines. In addition, intercellular interactions mediated by polyamines can coordinate the translational response to oxidative stress through the formation of stress granules. Some putative in vivo consequences of polyamine-mediated intercellular interactions are also discussed regarding cancer invasiveness and tissue regeneration.

Owing to preferential electrostatic adsorption of multivalent cations on highly anionic surfaces, natural multivalent polyamines and especially quadrivalent spermine can be considered as potential regulators of the complex dynamical properties of anionic MTs (microtubules). Indeed, the C-terminal tails of tubulin display many negative residues in a row which should enable the formation of a correlated liquid-like phase of multivalent counterions on its surface. Although it is known that polyamine counterions promote MT assembly in vitro, little is known about the relevance of this interaction in vivo. In the present study, we have explored the relationship between polyamine levels and MT assembly in HeLa and epithelial NRK (normal rat kidney) cells using DFMO (alpha-difluoromethylornithine), an irreversible inhibitor of ornithine decarboxylase, and APCHA [N-(3-aminopropyl)-N-cyclohexylamine], a spermine synthase inhibitor. Under conditions of intracellular polyamine depletion, the MT network is clearly disrupted and the MT mass decreases. Addition of spermine to polyamine-depleted cells reverses this phenotype and rapidly promotes the extensions of the MT network. Finally, we show that polyamine levels modulate the coating of MTs with MAP4 (MT-associated protein 4), an MT-stabilizing protein, and the spatial distribution of EB1 (end-binding protein 1), an MT plus-end-binding protein. In addition, polyamines favour the formation of gap junctions in NRK cells, a process which requires MT extensions at the cell periphery. The present study provides a basis for a better understanding of the role played by polyamines in MT assembly and establishes polyamine metabolism as a potential cellular target for modulating MT functions.

Background: Vagal hyperreactivity (VHR) is a frequent etiology of infant fainting spells; but it is sometimes difficult to diagnose. A biochemical test would therefore be useful, especially as the oculocardiac reflex (OCR) test innocuity is not absolute., Aims: To evaluate urinary excretions of norepinephrine, epinephrine and dopamine as markers for vagal hyperreactivity., Methods: During check-up of 55 infants from 0.5 to 11 months of age, for discomfort episodes, including OCR and Holter recording, 24h urinary assays of total norepinephrine, epinephrine and dopamine were carried out to evaluate sympathetic activity., Results: Epinephrine and norepinephrine urinary excretions were negatively correlated with VHR intensity, as measured by the OCR ECG parameters: RRmax, % cardiac deceleration and minimal frequency; dopamine excretion was not. When RRmax(OCR) was greater or equal to 800 ms, epinephrine urinary excretion tended to be less or equal to 9 nmol/mmol creatinine and norepinephrine excretion less or equal to 190 nmol/mmol creatinine., Conclusion: A delay in maturation of the sympathetic system and/or adrenomedullary glands with low secretion of norepinephrine and epinephrine inducing a desequilibrium of the sympathetic/parasympathetic balance may contribute to the fainting spells observed with VHR. Epinephrine and norepinephrine urinary excretions may provide informative complementary noninvasive markers for VHR., (2010 Elsevier Masson SAS. All rights reserved.)

Arginine homoeostasis is impaired in short bowel syndrome, but its supplementation in short bowel syndrome patients remains controversial. Recently, we demonstrated the benefits of citrulline supplementation by the enteral route in resected rats. Since the first step in managing short bowel syndrome is to initiate total parenteral nutrition, we hypothesized that parenteral citrulline supplementation would be more appropriate in this situation than arginine supplementation. In the present study, 24 rats were assigned to four groups. The sham group underwent transection whereas the three other groups underwent resection (R) of 80% of the small intestine. All rats were then fed exclusively by total parenteral nutrition as follows: supplementation with citrulline (R+CIT), with arginine (R+ARG) or no supplementation (R). All of the rats received isocaloric and isonitrogenous nutrition for 4 days. Nitrogen balance was measured daily. Rats were then killed and the blood was collected and the intestinal mucosa and extensor digitorum longus muscle were removed for amino acid and protein analysis. Citrulline and arginine increased mucosal protein content in the ileum (compared with sham and R, P<0.05). However, only citrulline prevented extensor digitorum longus atrophy (R+CIT, 130+/-3 mg compared with R, 100+/-6 mg and R+ARG, 110+/-2 mg, P<0.05). In addition, arginine worsened nitrogen balance (R+ARG, 104+/-46 mg/72 h compared with R, 249+/-69 mg/72 h, P<0.05). Only citrulline was able to prevent muscle atrophy and it was achieved independently from any noticeable effect on the gut in particular because citrulline and arginine share the same effect on mucosal ileal protein content. These results suggest that citrulline should be considered as a potential supplement for total parenteral nutrition of short bowel syndrome patients.

To gain further insight into the ability of ornithine alpha-ketoglutarate (OKG) to generate key metabolites, the aim of this work was to study the short-term metabolism, that is, 1 hour after administration, of OKG in plasma and tissues. Particular attention was paid to keto acids (alpha-ketoglutarate and branched-chain keto acids). Young (3 weeks old) male Wistar rats in the postabsorptive state received either 1.5 g/kg of monohydrated OKG (OKG group, n = 8) diluted in distilled water or an equivalent volume of saline solution at 0.9% (control group, n = 8) by gavage and were killed 1 hour later. Plasma, liver, jejunal and ileal mucosa, and the extensor digitorum longus muscle were removed to analyze amino and keto acid contents. Major metabolites detected after OKG ingestion (ornithine [ORN], alpha-ketoglutarate, proline and glutamate; OKG vs control, P < .05) and the absence of increased arginine (and even a decrease in jejunum and muscle) and citrulline levels suggested that ORN was mainly metabolized by the ORN aminotransferase pathway. In addition, significantly decreased plasma branched-chain keto acids and increased hepatic branched-chain amino acids (OKG vs control, P < .05) were observed upon OKG ingestion. Finally, glutamine accumulation restricted to the intestine, as evidenced in this short-term study, suggests that the effects of OKG on glutamine pools in other tissues in various pathological states after several days of treatment, as observed in previous studies, may be related to a long-term induction of glutamine synthetase.

Objective: Ornithine alpha-ketoglutarate (OKG) displays anabolic properties at the hepatic level, but the mechanisms involved remain unclear. This study investigated in vivo the ability of OKG to modulate hepatic gene expression of three liver-secreted proteins: albumin, transthyretin, and retinol binding protein., Methods: One hundred eighty rats were fed for 5 d with a balanced regimen enriched with OKG (5 g.kg(-1).d(-1)) or an isonitrogenous mixture (alanine, glycine, and serine). Hepatic mRNA levels and plasma concentrations of the three proteins studied were determined at the end of the nutrition period and after 1, 2, and 3 d of food deprivation. Results were compared by analysis of variance and Bonferroni-Dunn tests., Results: At the end of the nutrition period, hepatic mRNA levels and plasma concentrations of the three proteins were not modified by OKG supplementation. However, OKG largely increased mRNA levels of albumin, transthyretin, and retinol binding protein on the first day of starvation compared with control animals (+68%, +64% and +51%, respectively; P < 0.01 versus control). OKG precociously increased albuminemia (on day 2) but had no effect on plasma concentrations of transthyretin and retinol binding protein. Neither regulation of polyamine hepatic concentration nor alteration in hepatic amino acid content seemed to be implicated in these actions., Conclusion: This study is the first to demonstrate that OKG regulates in vivo liver gene expression during acute malnutrition by modulating hepatic mRNA levels.

Parasympathetic hyperactivity is found in some infants presenting faint episodes and could be responsible of certain Sudden Infant Death Syndrome cases. Therefore it was interesting to look for a noninvasive biochemical indicator of parasympathetic activity. A parasympaticomimetic syndrome associated with muscarinic receptor stimulation, which has been followed during 48 h, was obtained in the awake rat by reserpine injection (6.25 mg/kg at T0 and T24h), and a model of prolonged parasympatholytic syndrome, by administration of diphemanil-methylsulfate (DPMS), a muscarinic receptor inhibitor, in drinking water (mean daily dosis: 150 mg/kg). Significant bradycardia and tachycardia were respectively observed. In the reserpine-treated rats we found significantly increased cyclic guanosylmonophosphate (cGMP) urinary excretion between T24h and T48h, when compared with vehicle-treated controls (+87% in one experiment, +135% in the other, when expressed in pmol/microg creatinine); norepinephrine urinary excretion between T24h and T48h was decreased (-44%); the increase in cGMP urinary excretion was not significantly modified by the NO-synthase inhibitor, L-nitroarginine-methyl-ester. In the DPMS-treated rats, we observed a significantly decreased cGMP (-20%) and increased norepinephrine urinary excretion (+61%). Thus cGMP excretion varied in opposite directions in the reserpine- and DPMS-treated rats. The link between these modifications in cGMP excretion and muscarinic receptor stimulation or blockade has still to be fully demonstrated. Urinary cGMP excretion could be tested as screening parameter in infants at risk of faint episodes associated with bradycardia.

Fifty adult female Swiss albino mice were injected with either 1.11 mg/kg body weight pyridoxine or saline, subsequently they were all submitted to an immobilization stress with a complete fast for 17 h. At the end of this period, the animals were sacrificed, the gastric mucosa was dissected for ulcer count, and brain noradrenaline, dopamine and serotonin were determined by liquid chromatography. In addition, 26 nonstressed mice were used as controls, 16 of them being fed at libitum and 10 submitted to the same fasting period as the first two groups. In the stressed animals, the average number of gastric ulcers per mouse was twice as large in the saline-treated group than in the pyridoxine-treated group (p < 0.05). With a single exception, no ulcer was found in the non stressed controls. Brain norepinephrine content was almost identical in fasting controls and in stressed mice treated with pyridoxine; in the stressed animals treated with saline, the average norepinephrine content was higher by 15% and in the fed controls lower by 11% than in the two preceding groups. Pyridoxine treatment entailed a very significant reduction (p < 0.002) of norepinephrine variability, mainly due to the absence of high values (> or = 750 ng/g of fresh brain) which occurred only in the saline-treated group. Similar results were yielded for brain dopamine. No variations were observed for brain serotonin. These results suggest the antistress effect of pyridoxine.

AMMI MAJUS L., a plant belonging to the family Umbellifereae was found to possess a certain antischistosomal effect in mice infected with S. mansoni. This was proved by applying two techniques, the worm burden and the Oogram change. Bergapten, a pure furocoumarin naturally present in Ammi majus was found to have certain schistosomicidal effect.