[show abstract][hide abstract] ABSTRACT: L-carnitine-mediated beta-oxidation of fatty acids has a well established role in energy supply of oocytes and embryos. Disturbed carnitine metabolism may impair the reproductive potential in IVF and can serve as a biomarker of pregnancy outcome.
Our study was performed between March 24, 2011 and May 9, 2011. We performed 44 unselected IVF cycles, (aged 23--40 years (mean: 32.3+/-5.1 years) and had BMI of 17.3-34.7 (mean: 23.80+/-4.9). Samples were also obtained from 18 healthy women of similar age admitted for minor elective surgery to serve as control for plasma carnitine profile. Serum and follicular fluid (FF) free carnitine (FC) and 20 major acylcarnitines (ACs) were measured by ESI/MS/MS method.
Serum FC and AC levels in IVF patients were comparable to those in healthy control women. In FF FC and short-chain AC concentrations were similar to those in maternal serum, however, the levels of medium-chain, and long-chain AC esters were markedly reduced (p<0.05). The serum to FF ratio of individual carnitine compounds increased progressively with increasing carbon chain length of AC esters (p<0.05). There was a marked reduction in total carnitine, FC and AC levels of serum and FF in patients with oocyte number of >9 and/or with embryo number of >6 as compared to the respective values of <9 and/or <6 (p<0.05).
In IVF patients with better reproductive potential the carnitine/AC pathway appears to be upregulated that may result in excess carintine consumption and relative depletion of carnitine pool. Consequently, IVF patients may benefit from carnitine supplementation.
Reproductive Biology and Endocrinology 07/2013; 11(1):67. · 2.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objective. The present case-control study was undertaken to investigate l-arginine metabolism in pregnant women with early-onset and late-onset pre-eclampsia. Attempts were made to differentiate these two distinct diseases entities by using measured and derived parameters of l-arginine metabolism. Study design. Thirty-six patients with early-onset, 17 patients with late-onset pre-eclampsia and 15 healthy pregnant women at term were studied. Patients were categorized according to the weeks of gestation (< 34 vs. ≥ 34) at the appearance of clinical symptoms (hypertension + proteinuria). Venous samples were taken at gestational age of 29.8 ± 2.5, 36.1 ± 2.2 and 39.2 ± 1.2 weeks, respectively. L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), monomethylarginine (MMA) and l-ornithine were measured by LC-MS/MS method. L-arginine/ADMA, l-ornithine/l-arginine, ADMA/SDMA ratios and the arginine methylation index (arg-MI) were calculated. Results. Plasma levels of ADMA and MMA were significantly higher (p < 0.002) in pre-eclamptic patients than in healthy women. No significant differences could be detected between patients with early-onset and late-onset pre-eclampsia in either parameter studied. L-ornithine correlated positively with ADMA (r = 0.526, p < 0.001) and MMA (r = 0.533, p < 0.001) in the whole study population, and inversely with l-arginine (r = - 0.277, p < 0.044) in the pre-eclamptic group. When compared with maternal plasma in venous cord blood l-arginine was markedly reduced (p < 0.05) and there was a significant elevation in ADMA, SDMA, MMA and l-ornithine (p < 0.001, for each) without discernible differences between the study groups. Conclusions. Parameters of l-arginine metabolism do not discriminate the early-onset from late-onset pre-eclampsia. Our study provided indirect evidences for the redirection of l-arginine-NOS to the l-arginine-arginase pathway.
Scandinavian journal of clinical and laboratory investigation 06/2013; · 1.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: Distribution of aquaporin-4 (AQP4) was studied by western analysis and immunofluorescence in rat astrocytes exposed to either hypothermic (30 °C) or hyperosmolar (0.45 M sucrose) stress, and in the cerebrospinal fluid (CSF) of patients who suffered traumatic brain injury (TBI). CSF was obtained from 5 healthy subjects and from 20 patients suffering from severe TBI. CSF samples were taken at admission and on days 3 and 5-7. Here we report that, in response to both hypothermia and hyperosmolar stress, AQP4 was markedly reduced in cultured astrocytes. We also found that AQP4 significantly increased in patients with severe brain injury in respect to healthy subjects (P < 0.002). AQP4 in CSF remained unchanged in patients with elevated intracranial pressure (ICP), whereas there was a clear tendency to further increase in those patients whose ICP could be controlled within the normal range. We conclude that AQP4 levels in CSF are elevated after TBI and it might serve as a useful biochemical marker to assess brain water metabolism in clinical settings.
[show abstract][hide abstract] ABSTRACT: PURPOSE: Carnitine deficiency is common in end-stage renal disease (ESRD) patients receiving hemodialysis (HD) treatment. We investigated the effects of L: -carnitine supplementation on acyl carnitine (AC) profile and the changes of distinct ACs during a single HD session in long-term L: -carnitine pretreated ESRD patients. METHODS: Twenty non-diabetic adult patients and 37 healthy controls were studied. Blood samples were drawn before and after 12 weeks of carnitine supplementation, then hourly during an HD session, as well as 30 min after the end of the session. Free and individual AC plasma levels were determined by using ESI MS/MS technique. RESULTS: HD patients showed lower free- and total carnitine levels and elevated ACs and acyl/free carnitine ratio before carnitine supplementation. The L: -carnitine supplementation resulted in dramatic elevation of all carnitine esters. The HD session induced a progressive decline in free, short-chain, and dicarboxylic ACs (~80 % of pre-HD amount was washed out); the decrease of medium-chain ACs proved to be more moderate (~60 % washed out), whereas the long-chain ACs remained unaffected. Already 30 min after HD, a substantial increase was seen in free carnitine concentration (reaching 26 % of predialysis level) and the ACs also started to replenish (to 21-52 % of predialysis levels), without further exogenous carnitine load. CONCLUSIONS: The washout induced by HD session results in variable depletion of short-, medium-, and long-chain carnitine esters in carnitine-pretreated patients; the recovery of the circulating carnitine esters from the body stores occurs within 30 min after the cessation of the HD procedure.
International Urology and Nephrology 06/2012; · 1.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: L-carnitine supplementation is extensively used in patients on maintenance hemodialysis (HD) to improve dialysis-related clinical symptoms. In a series of studies, we investigated the dynamics of carnitine pool in carnitine-supplemented HD patients; here we report dramatic decrease with special changes of the ester profile due to interruption of the exogenous intake after the last HD session. Serum samples were collected from 18 L-carnitine-repleted end-stage renal disease (ESRD) patients before the L-carnitine supplementation, after completion of a carnitine supplementation period treatment (12 weeks, 1 g/IV/HD), right before the HD session, and 44 h after the dialysis. Levels of free carnitine (FC) and the individual esters were determined using electrospray MS/MS technique. Normally, L-carnitine supplementation causes significant elevation of all carnitine compounds to supraphysiological levels, which reaches a standard steady-state-like profile. In this study we found a dramatic decrease in the level of FC, and in short- and medium-chain acylcarnitines (ACs) 44 h after the last dialysis. At the end of this interdialytic period, FC levels increased to only 65% of the predialysis level, whereas the amounts of C2 and C3 esters recovered to only 50%. The level of C6 was 65% of the predialysis level, whereas the amount of C8 chain length ACs returned to 72% of the predialysis level. No significant change was seen in AC concentrations above C10 chain length. Omission of one single dosage of supplemental carnitine in long-term administration schemes results in dramatic decrease and reprofiling of carnitine esters even after the usual 44 h of interdialytic period.
[show abstract][hide abstract] ABSTRACT: This study was undertaken to compare the effects of vaginal delivery and cesarean section on the L-arginine-nitric oxide system by measuring levels of L-arginine, an endogenous nitric oxide synthase antagonist asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in the cord blood and postnatally.
Plasma samples were obtained from the umbilical vein and artery at birth and from peripheral venous blood on the second postnatal day in 30 full-term newborn infants: 10 born vaginally and 20 born by cesarean section.
After vaginal delivery, ADMA concentration was higher in the umbilical vein than in the umbilical artery (mean 1.06 vs 0.90 µmol/L [P = 0.027]); and ADMA level fell after birth to 0.66 µmol/L on the second postnatal day (P = 0.007 vs umbilical artery). Newborns born by cesarean section had similar ADMA levels in umbilical arterial and venous blood, 1.19 and 1.18 µmol/L, and the ADMA level fell to 0.84 µmol/L by the second postnatal day (P < 0.001). Vaginal birth induced neither significant umbilical venoarterial difference nor a postnatal fall in SDMA. After cesarean section, SDMA was essentially the same in umbilical vein, umbilical artery and postnatal peripheral vein samples. At 2 days of age, both ADMA and SDMA levels stayed higher in infants born by cesarean section than in vaginally born infants.
ADMA level falls after both vaginal and cesarean birth, whereas SDMA level does not. The higher ADMA level after cesarean birth compared with vaginal birth may contribute to decreased nitric oxide production and bioavailability in neonatal vascular beds.
Pediatrics International 02/2012; 54(4):476-9. · 0.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: We measured and compared serum asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-arginine levels in patients undergoing coronary artery revascularization.
Two groups of patients with coronary artery disease were subjected to coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass (CPB; n = 20) or with off-pump CABG surgery (OPCABG; n = 21). Blood samples for measurements of ADMA, SDMA, and L-arginine were withdrawn and determined by liquid chromatography-tandem mass spectrometry from the coronary sinus (CS) and from the peripheral vein.
On the basis of the intraoperative (CS) samples, ADMA levels rose in the CPB group (F = 0.416, P < 0.685 and F = 14.751, P < 0.001 for OPCABG and CPB groups, respectively). A similar significant increase of ADMA was observed in the peripheral blood (F = 30.738, P < 0.001) during CPB, whereas ADMA levels remained unchanged during OPCABG. The time course of L-arginine levels was significantly different in the blood samples from CS (F = 3.255, P<0.05), when compared with samples from the peripheral blood (F = 3.255, P < 0.05). The values of the L-arginine/ADMA ratio were significantly higher in the OPCABG group at baseline and on the first postoperative day compared with the results of the CPB group (178.29 ± 11.56 vs. 136.28 ± 13.72 and 129.43 ± 7.08 vs. 106.8 ± 6.9 for OPCABG and CPB groups, respectively).
Plasma levels of ADMA, SDMA, L-arginine, and L-arginine/ADMA ratio are reliable and feasible markers of an early ischemia-reperfusion injury. During CPB operation, the plasma concentration of ADMA increased significantly and remained elevated until the first postoperative day due to extensive ischemia-reperfusion injury caused by CPB.
[show abstract][hide abstract] ABSTRACT: The present study was undertaken to reveal the influence of intracerebroventricular (ICV) benzamil on the dynamics of brain water accumulation in hyponatremic rats. Parameters of brain water homeostasis were continuously monitored, using in vivo magnetic resonance imaging (MRI) methods. The results were compared with those obtained in a previous study by tissue desiccation.
A 3-T MRI instrument was applied to perform serial diffusion-weighted imaging to measure the apparent diffusion coefficient (ADC) and MR spectroscopy to determine water signal. A decrease of ADC is thought to represent an increase of intracellular water, whereas water signal is used to quantify brain water content. Five groups of male Wistar rats were studied as follows: normonatremic, native animals (group NN, n = 7), hyponatremic animals (group HN, n = 8), hyponatremic animals treated with ICV benzamil (group HNB, n = 8), hyponatremic animals treated with ICV saline (group HNS, n = 5) and normonatremic animals treated with ICV benzamil (group NNB, n = 5). Hyponatremia was induced by intraperitoneal administration of 140 mmol/l dextrose solution in a dose of 20% of body weight. Benzamil hydrochloride (4 μg) was injected ICV to the treated animals.
During the course of hyponatemia, ADC declined steadily from the baseline (100%) to reach a minimum of 92.32 ± 3.20% at 90 min (p < 0.0005). This process was associated with an increase in water signal to a maximum of 5.95 ± 2.62% at 100 min (p < 0.0005). After pretreatment with benzamil, no consistent changes occurred either in ADC or in water signal.
These findings suggest that sodium channel blockade with ICV benzamil has an immediate protective effect against the development of hyponatremic brain edema. Sodium channels, therefore, appear to be intimately involved in the initiation and progression of brain water accumulation in severe hyponatremia.
[show abstract][hide abstract] ABSTRACT: Here we report the serum carnitine ester profile during and after 1g iv/day L-carnitine supplementation in haemodialysis patients.
Seven patients were studied over 29 weeks. After a control day, 12 weeks of replacement therapy was introduced followed by 17 weeks of washout period. The serum acylcarnitine concentrations were determined by isotope dilution ESI MS/MS technique.
At baseline significantly decreased free carnitine (48%, p < 0.01) and a 1.5-16-fold elevation of 16 out of 27 acylcarnitines were detected in HD patients compared with the controls. On the last day of L-carnitine supplementation a 1.6-4.8-fold increase was observed in the acylcarnitine levels compared with day 0; the increase-profile was achieved in four different patterns. The increase rate was rapid and early saturable for C5, C5OH, C6DC, C8:1, C10DC and C18:2 esters, slower for C2, C4, C6, C18 and C18:1 esters, it was slowest and reached a late plateau for C3, C8DC, C14:2, C16 and C16:1, and finally almost gradual increase was seen for 11 acylcarnitines. Three months after the cessation of carnitine treatment marked concentration drops were found for almost all acylcarnitines (by 11-74 % of week 12, p < 0.05); the values further decreased over the five remaining weeks of the observation period.
Carnitine administration affected the levels of circulating esters in different dynamics and kinetics suggesting a regulated, non-random adaptive reallocation of nutrients. A considerable washout was achieved 3 months after discontinuation of the supplementation; however, the profile still was suggestive for presence of rest of accumulated supplement.
Scandinavian journal of clinical and laboratory investigation 03/2011; 71(4):280-6. · 1.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: The study was designed to compare the response pattern of plasma l-arginine and methylarginines to stent placement in patients with or without ST segment elevation myocardial infarction (STEMI). Two groups of patients with obstructive coronary artery disease (OCAD) undergoing percutaneous coronary intervention (PCI) with stenting were enrolled in the study. Group I consisted of 16 patients with STEMI, whereas group II included 24 patients without STEMI (controls). Before PCI and at <1 h, 5 and 30 days after reperfusion, blood samples were taken for measurement of l-arginine and methylarginines. L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), N-monomethylarginine (MMA) and l-ornithine plasma levels were measured by LC-MS-MS. Arginine methylation index (Arg-MI) was calculated according to the formula, Arg-MI = (ADMA+SDMA)/MMA. In patients without STEMI, stenting induced a prompt and sustained depression of ADMA (p<0.000), and l-ornithine (p<0.000) with simultaneous increase of l-arginine (p<0.001), l-arginine/ADMA ratio (p<0.000) and an inconsistent change in MMA. Arg-MI remained at the baseline value. By contrast, STEMI patients responded to stent placement with a variable increase in l-arginine (p<0.01), ADMA (p<0.069), SDMA, MMA (p<0.01) and l-ornithine (p<0.000), whereas there was an early fall of Arg-MI after stenting, followed by a steady increase approaching the initial values. The differences in the time-course for ADMA (p<0.000), MMA (p<0.007), Arg-MI (p<0.01) and l-ornithine (p<0.003) proved to be significant between the STEMI and control group. It can be concluded therefore, that stent placement improves endothelial dysfunction in patients with OCAD when it is not complicated by STEMI.
International Journal of Molecular Medicine 04/2010; 25(4):617-24. · 1.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: The concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is increased in patients with coronary heart disease (CHD). The potential effect of percutaneous coronary intervention (PCI) with stent placement on ADMA plasma level in CHD patients has not yet been investigated. Concentrations of ADMA, L-arginine, symmetric dimethylarginine (SDMA), and L-ornithine were measured in the plasma of 30 CHD patients 24 h before, and 1 h, 5 days, and 30 days following PCI with bare-metal stent or drug-eluting stent placement (stent group) and in the plasma of 20 patients without CHD who underwent angiography alone (control group). A repeated measures ANOVA revealed the significant time by group interaction for ADMA (F=12.8, p<0.0001), SDMA (F=5.5, p=0.013), L-ornithine (F=12.5, p<0.0001), L-aginine (F=4.7, p=0.013) and L-arginine/ADMA ratio (F=7.1, p<0.001). Post-hoc ANOVAs showed that this interaction was due to the fact that control patients without stent placement responded to the coronary angiography with a significant increase in ADMA (F=4.4, p=0.009), SDMA (F=4.7, p=0.007) and L-ornithine (F=28.3, p<0.0001) levels, whereas the stent implantation independent of the stent type used significantly reduced the cardiovascular risk factor ADMA (F=10.8, p<0.0001). Thus, the current study demonstrates that in patients with CHD, PCI stent placement markedly decreases the plasma level of cardiovascular risk factor ADMA. Coronary angiography alone results in an increase of ADMA. We conclude that the stent effect on ADMA level cannot be explained by unspecific effects of the coronary angiography and is independent of the stent type used.
International Journal of Molecular Medicine 06/2009; 23(5):651-7. · 1.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: It has been recently shown that A6 cells exposed to hyponatraemic stress respond with increased sodium uptake via activation of benzamil-sensitive sodium channels. This study was performed, therefore, to explore the possible involvement of benzamil-sensitive sodium channels and cellular sodium influx in brain oedema formation in hyponatraemic rats.
Four groups of male Wistar rats were studied (n = 13 in each group). Animals in group I with normonatraemia received intracerebroventricular (icv) 0.9% NaCl; animals in group II-IV were made hyponatraemic by intraperitoneal administration of isotonic glucose solution in a dose of 20% per body weight. Rats were pretreated with icv 0.9% NaCl (group II), 120 microg arginine vasopressin (AVP) (group III) or 4 microg benzamil-hydrochloride (group IV). Plasma sodium (ion-selective electrode) plasma osmolality (vapour pressure osmometer) and brain sodium and potassium content (flame photometer) as well as brain water content (desiccation method) were measured after a 2-h hydration period.
Plasma sodium, osmolality and tissue sodium and potassium contents were markedly depressed in hyponatraemic rats (group II-IV, p < 0.0005 for each group) irrespective of drug pretreatment. Brain water content, however, responded to hyponatraemia with an increase from 77.55 +/- 1.00% to 78.45 +/- 0.94% (p < 0.01), and it was further augmented to 79.35 +/- 0.80% (p < 0.0005) by icv AVP pretreatment. By contrast, benzamil administration prevented the rise of brain water caused by hyponatraemia (77.61 +/- 1.04%).
Early in the course of hyponatraemia, brain sodium channels may be activated, and the subsequent cellular sodium uptake may generate osmotic gradient to allow passive water flow into the cells. The simultaneous reduction of osmotic water conductivity of brain-specific aquaporin-4 by hyponatraemia, however, may limit water accumulation.
[show abstract][hide abstract] ABSTRACT: Recent reports suggest that adipokines are potent modulators of inflammation. We tested the hypothesis that the decreased food intake and the acute liver disease might be associated with changes of serum ghrelin, adipokines and insulin levels.
Fasting ghrelin, adiponectin, leptin, resistin and insulin were measured in 25 children suffering from acute viral hepatitis, caused by either hepatitis A or Epstein-Barr viruses. The age of the patients ranged from 2.2 to 17.2 years (mean: 10.4 years); 10 male and 15 female. Samples for hormones and liver function tests were drawn at 08 : 00 to 09 : 00 h after an overnight fast. The first samples were collected in the morning after the day of admission, the second samples after 2 months of recovery.
Ghrelin and adiponectin levels were significantly higher during hepatitis than after recovery (831.4+/-276.44 vs. 736.21+/-274.91 pg/ml, P<0.0001; and 22.91+/-12.93 vs. 15.16+/-8.81 microg/ml, P<0.001, respectively). Adiponectin levels correlated significantly with age-specific and sex-specific body mass index-matched percentile values as well (P=0.0062). Linear regression analysis confirmed that there was a significant association of changes in serum ghrelin and resistin levels and the severity of hepatitis (P=0.005; P<0.05). We could verify a marginal relationship of the changes of serum leptin and the severity of the disease (P=0.0646).
This study confirms that there are significant changes in serum levels of ghrelin, and adipokines in disease-associated malnutrition and acute hepatitis.
European journal of gastroenterology & hepatology 04/2009; 21(7):739-43. · 1.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: The endothel dysfunction in early life may play a role in developmental programming of cardiovascular morbidity. The changes of dimethylarginines' plasma levels during the first month among preterm infants and their determinants had been investigated in our study.
Twenty preterm infants of healthy mothers were studied. Mean (+/-SD) birth weight and gestational age were 919.5 +/- 235.5 g and 26.7 +/- 1.6 weeks, respectively. Blood samples were taken by venipuncture at the 3rd, 7th, 14th, 21st and 28th days. Plasma concentrations of L-arginine, asymmetric and symmetric dimethylarginine (SDMA) were measured by liquid chromatography-mass spectrometry method, evaluated by multivariate linear regression analysis.
L-arginine (p < 0.001) and asymmetric dimethylarginine (ADMA) levels (p < 0.001) were positively associated with postnatal age. ADMA levels were negatively correlated with gestational age (p = 0.007), dopamine-need on the 3rd day of life (p = 0.015) and late infection (p = 0.038). The higher birth weight was associated with higher L-arginine (p = 0.052) and ADMA (p = 0.002) concentrations. The dopamine-need on the 7th day of life had a significant effect on postnatal elevation of SDMA levels (p = 0.035).
The progressive increase of ADMA levels described by our study among preterm infants suggests that early endothel dysfunction may take part in developmental programming of chronic adult diseases.
[show abstract][hide abstract] ABSTRACT: To define the role of asymmetric dimethylarginine (ADMA) in the control of blood pressure (BP) during hemodialysis (HD).
L-Arginine, ADMA and symmetric dimethylarginine (SDMA) levels of patients with (n = 18) or without (n = 13) hypotensive episodes during HD sessions were measured before and after HD treatment by liquid chromatography-mass spectrometry. Clinical variables, laboratory parameters and underlying pathologies of end-stage renal disease (ESRD) were comparable in the groups. BP was serially recorded.
In patients with ESRD, plasma dimethylarginines were markedly elevated and decreased significantly by the end of the HD sessions. ADMA levels in patients having hypotensive episodes during HD were significantly higher than in those maintaining their BP (before HD: 0.62 +/- 0.11 micromol/l vs. 0.71 +/- 0.13 micromol/l, p = 0.04; after HD: 0.31 +/- 0.11 micromol/l vs. 0.43 +/- 0.11 micromol/l, p = 0.01). There was a significant inverse relationship of the minimum systolic and diastolic BP during HD to the predialysis ADMA levels (for systolic BP r = -0.50, p < 0.01; for diastolic BP r = -0.59, p < 0.01) and to the postdialysis ADMA levels (for systolic BP r = -0.49, p < 0.01; for diastolic BP r = -0.51, p < 0.005), respectively.
It is suggested that excessive NO generation is involved in the HD-associated hypotension and induces an increase in plasma ADMA levels to prevent further fall in BP.
Nephron Clinical Practice 02/2008; 108(2):c127-34. · 1.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: The composition and exact structure of the non-cellular mesangial matrix in the glomerulus of the human kidney are a matter of debate. It may appear like a structure similar to the glomerular basement membrane (GBM), it has been described to contain microfilaments. The exact transport route of fluids, solvents and immunocomplexes in the mesangium is not well-known either. We know that in some glomerular diseases immunocomplexes can be found in the GBM and the mesangium at the same time in the same patient. A possible explanation of the above findings could be provided by our hypothesis, i.e. the existence of a well-defined mesangial channel network (MChN). This MChN would consist of intercommunicating channels, which were embedded into the spongy cytoplasm of the mesangial cells (MCs) and surrounded by the plasma membrane of the mesangial cells. The MChN would lead from the subendothelial space through deep mesangium to the vascular pole or the juxtaglomerular apparatus and may transport fluid and other materials such as immunocomplexes into the mesangium. It would be continuous with the GBM. Microfilaments of the MC would be anchored to the walls of the MChN regulating its diameter, thus mesangial fluid transport and pressure. The dilatation of these channels by mechanical obstruction could contribute to glomerular sclerosis. The hypothesis can be challenged by methods like electronmicroscopy, immunoelectronmicroscopy, confocal laser-scanning microscopy, and vital stain studies. We provide some images suggesting the existence of the channel and its connection with the GBM. If the hypothesis was true, it could contribute to understanding of mesangial transport processes, pressure regulation and pathogenesis of glomerular mesangial diseases.
[show abstract][hide abstract] ABSTRACT: Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), are assumed to be related to delayed vasospasm after subarachnoid haemorrhage (SAH). However, data on CSF concentrations of L-arginine, ADMA and its structural isomer symmetric dimethylarginine (SDMA) are very sparse in humans. We here present a new hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS-MS) method for the precise determination of these substances in CSF. The method requires only minimal sample preparation and features isotope labeled internal standards. First data of patients with SAH showed that on the day of admission CSF concentration values of L-arginine and ADMA were not significantly different from controls, but increased markedly during the course of the hospital stay. The decrease of the L-arginine to ADMA ratio points to a progressive impairment of the NO production rate in the brain after SAH which is confirmed by a simultaneous decrease in nitrate and nitrite concentrations in CSF.
Journal of Neuroscience Methods 09/2007; 164(1):155-60. · 2.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Experimental and clinical evidence has been accumulated to indicate that elevated plasma asymmetric dimethylarginine (ADMA) levels can be regarded as a marker of endothelial dysfunction that mediates cardiovascular morbidity by impairing NO-dependent vascular reactions; therefore, it may have a role in the cardiopulmonary adaptation of the neonate. The present study was undertaken to investigate the perinatal NO metabolism by measuring L-arginine, the NO synthase substrate, ADMA, the endogenous inhibitor of NO synthase, and symmetrical dimethylarginine (SDMA), the biologically inactive L-arginine metabolite in umbilical venous and arterial plasma and in peripheral plasma of the neonate. Measurements were done in ten healthy pregnant women at term delivery and in their newborn infants on the second day of life by using liquid chromatography-mass spectrometry method. It was demonstrated that cord blood L-arginine, ADMA, and SDMA levels were markedly elevated with a moderate, but consistent veno-arterial difference suggesting that they are mainly generated by the placental endothelium. L-Arginine and ADMA levels were found to fall significantly (p < 0.001) by the second postnatal day, whereas SDMA remained unaltered. This finding indicates accelerated enzymatic ADMA elimination and reduction in the inhibition of NO-synthase activity. It is concluded that ADMA may play a role in the control of feto-placental circulation and the circulatory adaptation of the neonate.
[show abstract][hide abstract] ABSTRACT: Aquaporin-1 and aquaporin-4, water channel membrane proteins reported in both experimental animals and in adult humans, have been detected in different, non-overlapping areas of the central nervous system. This immunohistochemical study describes the developmental expression pattern of the water channel membrane proteins, aquaporin-1 and aquaporin-4, in various structures of human fetal brain over the gestational period of 14-40 weeks. Aquaporin-1 immunostaining was exclusively found in the epithelial cells of the choroid plexus from the 14th gestational week, and the staining pattern altered slightly over time. At week 14, immunostaining appeared only in the apical cell membranes. By the 18th gestational week, the entire plasma membrane of these apical cells was immunopositive, as well as was the cytosol. These changes in immunoreactivity indicate an increasing production of aquaporin-1 in the epithelial cells during the period between the 14th and 24th weeks of gestation. Aquaporin-4 immunostaining was first detected in the archicortex, from gestational week 14 and was detected in the neocortex, 6-7 weeks later. Immunostained structures were always astrocytes, particularly the astrocytic endfeet in the ventricular wall, at the developing ependymal lining, at the pial surface, and around the capillaries. Neuronal labeling was not observed. These results in human fetal brain lend morphological support to the previous findings that aquaporin-1 and aquaporin-4 play different roles in the regulation of the water homeostasis of the brain.
International Journal of Developmental Neuroscience 09/2006; 24(5):295-305. · 2.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: We studied the association between genetic polymorphisms of the renin-angiotensin system and the risk for circulatory failure (CF) during the first three postnatal days in 104 very-low-birthweight preterm infants. CONCLUSION: Infants with angiotensin-converting enzyme DD genotype were protected against CF (adjusted OR 0.41, 95% CI 0.19-0.89).