Novel insights into human endometrial paracrinology and embryo-maternal communication by intrauterine microdialysis.
(1/2093)
The regulation of human implantation is still unknown. Evidence from mice suggests an essential role for several paracrine mediators but species differences with implantation in the human preclude the extrapolation of these concepts to humans. An intrauterine microdialysis device (IUMD), consisting of microdialysis tubing glued into a balloon catheter on one side and into a polypropylene tube on the other, allows a dynamic and accurate in-vivo measurement of uterine paracrine interactions in humans. Inserted into the uterine cavity in the form of a loop, it can be continuously perfused with saline to reveal a number of relevant cytokines and growth factors in uterine effluents of non-pregnant women in both follicular and luteal phases. These included interleukin (IL)-1alpha, IL-1beta, IL-6, leukaemia inhibitory factor (LIF), macrophage colony-stimulating factor (M-CSF), epidermal growth factor, vascular endothelial growth factor (VEGF), insulin-like growth factor binding protein-1 (IGFBP-1), prolactin, and human chorionic gonadotrophin (HCG). The source of intrauterine HCG is unclear since endometrial mRNA for the HCG beta-subunit is not revealed using reverse transcriptase polymerase chain reaction analysis. Applying urinary HCG locally via the IUMD profoundly alters endometrial secretory parameters. Prolactin, IGFBP-1, and M-CSF are significantly inhibited and VEGF is regulated in a biphasic manner involving early stimulation followed by inhibition of intrauterine levels. Use of the IUMD has thus shown that the urinary HCG preparations routinely used for ovulation induction and luteal support may directly alter endometrial function. (+info)
N-Acetylaspartate distribution in rat brain striatum during acute brain ischemia.
(2/2093)
Brain N-acetylaspartate (NAA) can be quantified by in vivo proton magnetic resonance spectroscopy (1H-MRS) and is used in clinical settings as a marker of neuronal density. It is, however, uncertain whether the change in brain NAA content in acute stroke is reliably measured by 1H-MRS and how NAA is distributed within the ischemic area. Rats were exposed to middle cerebral artery occlusion. Preischemic values of [NAA] in striatum were 11 mmol/L by 1H-MRS and 8 mmol/kg by HPLC. The methods showed a comparable reduction during the 8 hours of ischemia. The interstitial level of [NAA] ([NAA]e) was determined by microdialysis using [3H]NAA to assess in vivo recovery. After induction of ischemia, [NAA]e increased linearly from 70 micromol/L to a peak level of 2 mmol/L after 2 to 3 hours before declining to 0.7 mmol/L at 7 hours. For comparison, [NAA]e was measured in striatum during global ischemia, revealing that [NAA]e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [14C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA. (+info)
Determination of free interstitial concentrations of piperacillin-tazobactam combinations by microdialysis.
(3/2093)
The investigation of tissue penetration and distribution of antibiotics is of great importance, since infections occur mostly in the tissues. The aim of this study was to investigate the pharmacokinetics of piperacillin and tazobactam, alone and in combination, by measuring total plasma and free interstitial concentrations, and to examine the relationship between free levels of both drugs in blood and those in the extracellular space. Piperacillin and tazobactam were administered, alone and in combination, to anaesthetized rats as a single iv bolus dose. Total plasma concentrations and free extracellular concentrations were quantified by HPLC. In-vivo microdialysis sampling was used to study the free tissue distribution patterns of both drugs. The pharmacokinetics of piperacillin and tazobactam in plasma were consistent with a two-compartment body model. Piperacillin pharmacokinetics were not influenced by co-administration of tazobactam. Tazobactam's volumes of distribution and clearance were decreased by the co-administration of piperacillin and the area under the curve was significantly increased. Comparisons between calculated free concentrations in the peripheral compartment for both drugs and measured free extracellular concentrations revealed excellent agreement. For piperacillin and tazobactam, alone and in combination, predictions of the concentration-time profiles of free drug in the peripheral compartment can be made on the basis of plasma data. (+info)
Effects of mCPP on the extracellular concentrations of serotonin and dopamine in rat brain.
(4/2093)
Intravenous administration of m-chloro-phenylpiperazine (mCPP) (0.25 or 2.5 mg/kg) induced a marked and dose-related increase in extracellular concentrations of serotonin in hippocampus (300-1,400% of baseline) as measured using in vivo microdialysis in awake male Wistar rats of the spontaneously hypertensive (SH) strain. Indicating that the effect of mCPP was caused by a reversal of the serotonin transporter, it was antagonized by pretreatment with the serotonin re-uptake inhibitor citalopram (10 mg/kg) but was unaffected by local administration of the sodium channel blocker tetrodotoxin (TTX; 1 microns). mCPP was also shown to induce an increase in extracellular concentrations of dopamine in the nucleus accumbens and the striatum of SH rats and in the nucleus accumbens of rats of the Sprague-Dawley (SD) strain; this effect of mCPP was, however, much weaker (125-170% of baseline) than the effect on serotonin; moreover, it seems to be TTX-sensitive. In anesthetized SD rats, mCPP induced a moderate reduction of nigral dopamine cell firing rate; supporting the assumption that this effect is secondary to the observed increase in dopamine release, it was blocked by pretreatment either with the dopamine synthesis inhibitor alpha-methyl-para-tyrosine or with the dopamine D2 receptor antagonist haloperidol. In conclusion, the results suggest that mCPP induces a marked, TTX-insensitive increase in serotonin release in rat brain, but only a modest and TTX-sensitive increase in the extracellular levels of dopamine. (+info)
Estimation of rat muscle blood flow by microdialysis probes perfused with ethanol, [14C]ethanol, and 3H2O.
(5/2093)
We used the perfused rat hindquarter to evaluate whether the microdialysis ethanol technique can be used to qualitatively estimate nutritive skeletal muscle blood flow. Four microdialysis probes were inserted in different hindlimb muscles in each of 16 rats. Hindquarters were perfused at blood flow rates ranging from 0 to 21 ml. 100 g-1. min-1. The microdialysis probes were perfused at 2 microliter/min with perfusate containing ethanol, [14C]ethanol, and 3H2O. Within and between experiments outflow-to-inflow ratios (o/i) generally varied inversely with blood flow. When a low flow or no flow was maintained in hindquarters, o/i ratios first increased with time (for at least 60 min) and then leveled off. The long time constant impaired detection of rapid oscillations in blood flow, especially at low blood flow rates. Contractions per se apparently decreased o/i ratios independent of blood flow. Ethanol and [14C]ethanol o/i ratios did not differ. 3H2O o/i paralleled ethanol and [14C]ethanol o/i ratios but it was significantly lower. In conclusion, differences in skeletal muscle blood flow can be detected by the microdialysis technique. However, the slow changes in o/i, in particular at low blood flow rates, limit the usefulness of the technique for measuring dynamic changes in blood flow; caution must also be exerted during muscle contractions. 3H2O and [14C]ethanol are good alternatives to ethanol in the determination of blood flow by microdialysis. (+info)
Metabolism and inflammatory mediators in the peritendinous space measured by microdialysis during intermittent isometric exercise in humans.
(6/2093)
1. The metabolic processes that occur around the tendon during mechanical loading and exercise are undescribed in man. These processes are important for understanding the development of overuse inflammation and injury. 2. A microdialysis technique was used to determine interstitial concentrations of glycerol, glucose, lactate, prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) as well as to calculate tissue substrate balance in the peritendinous region of the human Achilles tendon. Recovery of 48-62 % (range) at rest and 70-77 % during exercise were obtained for glycerol, glucose and PGE2. 3. Six young healthy humans were studied at rest, during 30 min of intermittent static plantar flexion of the ankle at a workload corresponding to individual body weight, and during 60 min of recovery. Microdialysis was performed in both legs with simultaneous determination of blood flow by 133Xe washout in the same area, and blood sampling from the radial artery. 4. With exercise, the net release of lactate as well as of glycerol from the peritendinous space of the Achilles tendon increased 2-fold (P < 0.05). Furthermore a 100 % increase in interstitial concentration of PGE2 and TXB2 was found, but it was only significant for TXB2(P < 0.05). As peritendinous blood flow increased 2- to 3-fold during intermittent static contractions, this indicates also that the output of these substances from the tissue increased during exercise. 5. This study indicates that both lipid and carbohydrate metabolism as well as inflammatory activity is accelerated in the peritendinous region of the human Achilles tendon with dynamic loading. (+info)
Evaluation of the microdialysis technique in the dog fat pad.
(7/2093)
In the present study the microdialysis technique was evaluated in an isolated autoperfused dog fat pad. Concentrations of glucose, lactate, and glycerol were measured in interstitial fluid by microdialysis and simultaneously in arterial and adipose venous plasma. Adipose tissue blood flow was measured by both 133Xe washout and timed weighing of venous blood. Metabolite concentrations in adipose venous plasma calculated from interstitial and arterial metabolite concentrations and 133Xe washout were positively correlated with measured venous concentrations (glucose: r = 0.95, lactate: r = 0.92, glycerol: r = 0.81). Calculated and measured venous plasma concentrations did not differ for either glucose or lactate, but for glycerol, calculated concentration was on average 76% of measured concentration. Metabolite exchanges (Fick's principle) calculated from interstitial metabolite concentrations were positively correlated with measured exchanges only for lactate (r = 0.69). In conclusion, metabolite concentrations in adipose venous plasma can be calculated from microdialysis measurements with greater accuracy for glucose and lactate than for glycerol. The precision, however, is too low to allow calculation of metabolite exchange when arteriovenous metabolite differences are low. (+info)
We recently described a perivascular sensory nerve-linked dilator system that can be activated by interstitial Ca2+ (Ca2+isf). The present study tested the hypothesis that Ca2+isf in the rat duodenal submucosa varies through a range that is sufficient to activate this pathway. An in situ microdialysis method was used to estimate Ca2+isf. When the duodenal lumen was perfused with Ca2+-free buffer, Ca2+isf was 1.0 +/- 0.13 mmol/l. Ca2+isf increased to 1.52 +/- 0.04, 1.78 +/- 0.10, and 1.89 +/- 0.1 when the lumen was perfused with buffer containing 3, 6, and 10 mmol/l Ca2+, respectively (P < 0.05). Ca2+isf was 1.1 +/- 0.06 mmol/l in fasted animals and increased to 1. 4 +/- 0.06 mmol/l in free-feeding rats (P < 0.05). Wire myography was used to study isometric tension responses of isolated mesenteric resistance arteries. Cumulative addition of extracellular Ca2+-relaxed serotonin- and methoxamine-precontracted arteries with half-maximal effective doses of 1.54 +/- 0.05 and 1.67 +/- 0.08 mmol/l, respectively (n = 5). These data show that duodenal Ca2+isf undergoes dynamic changes over a range that activates the sensory nerve-linked dilator system and indicate that this system can link changes in local Ca2+ transport with alterations in regional resistance and organ blood flow. (+info)