Hydrogen sulphide as a signalling molecule regulating physiopathological processes in gastrointestinal motility.

The biology of H2 S is a still developing area of research and several biological functions have been recently attributed to this gaseous molecule in many physiological systems, including the cardiovascular, urogenital, respiratory, digestive and central nervous system (CNS). H2 S exerts anti-inflammatory effects and can be considered an endogenous mediator with potential effects on gastrointestinal motility. During the last few years, we have investigated the role of H2 S as a regulator of gastrointestinal motility using both animal and human tissues. The aim of the present work is to review published data regarding the potential role of H2 S as a signalling molecule regulating physiopathological processes in gastrointestinal motor function. H2 S is endogenously produced by defined enzymic pathways in different cell types of the intestinal wall including neurons and smooth muscle. Inhibition of H2 S biosynthesis increases motility and H2 S donors cause smooth muscle relaxation and inhibition of propulsive motor patterns. Impaired H2 S production has been described in animal models with gastrointestinal motor dysfunction. The mechanism(s) of action underlying these effects may include several ion channels, although no specific receptor has been identified. At this time, even though there is much experimental evidence for H2 S as a modulator of gastrointestinal motility, we still do not have conclusive experimental evidence to definitively propose H2 S as an inhibitory neurotransmitter in the gastrointestinal tract, causing nerve-mediated relaxation.

P2Y(1) receptors mediate purinergic relaxation in the equine pelvic flexure.

In the equine large intestine, the knowledge of the basic mechanisms underlying motility function is crucial to properly treat motility disorders. P2Y1 receptors are responsible for mediating purinergic colonic relaxation in several species. In vitro experimental studies of the circular muscle from the equine pelvic flexure (n = 6) were performed to characterize inhibitory and excitatory neuromuscular transmission. Electrophysiological studies showed that electrical field stimulation (EFS) evoked biphasic inhibitory junction potentials (IJPs) in smooth muscle cells: a fast IJP (IJPf) followed by a sustained IJP (IJPs). IJPs was sensitive to L-NNA 1 mM (a nitric oxide synthase inhibitor) (P <0.01), while IJPf was abolished by MRS2500 1 µM (a P2Y1 receptor antagonist) (P <0.001). EFS (5 Hz for 2 min) in the organ bath inhibited rhythmic contractions to 3.0 ± 2.5% of basal area under the curve (P <0.0001). EFS under MRS2500 1 µM or L-NNA 1 mM incubation inhibited contractions to 6.0 ± 2.8% (P <0.05) and 24.4 ± 11.3% respectively (P <0.05). Combination of MRS2500 1 µM and L-NNA 1 mM completely reversed the EFS-induced inhibition of colonic motility. Non-nitrergic, non-purinergic conditions were used to reveal voltage-dependent EFS-induced contractions sensitive to atropine 1 µM (P <0.001) and, therefore, cholinergic. In conclusion, nerve-mediated relaxation and contraction in the equine pelvic flexure involve the same mechanisms as those observed in the human colon. P2Y1 receptors mediate purinergic relaxations and are potential targets for the treatment of equine colonic motor disorders.

Inverse gradient of nitrergic and purinergic inhibitory cotransmission in the mouse colon.

AIM: Gastrointestinal smooth muscle relaxation is accomplished by the neural corelease of ATP or a related purine and nitric oxide. Contractions are triggered by acetylcholine and tachykinins. The aim of this work was to study whether regional differences in neurotransmission could partially explain the varied physiological roles of each colonic area. METHODS: We used electrophysiological and myography techniques to evaluate purinergic (L-NNA 1 mm incubated tissue), nitrergic (MRS2500 0.3 µm incubated tissue) and cholinergic neurotransmission (L-NNA 1 mm and MRS2500 0.3 µm incubated tissue) in the proximal, mid and distal colon of CD1 mice (n = 42). RESULTS: Purinergic electrophysiological responses elicited by single pulses (28 V) were greater in the distal (IJPfMAX = -35.3 ± 2.2 mV), followed by the mid (IJPfMAX = -30.6 ± 1.0 mV) and proximal (IJPfMAX = -11.7 ± 1.1 mV) colon. In contrast, nitrergic responses decreased from the proximal colon (IJPsMAX = -11.4 ± 1.1 mV) to the mid (IJPsMAX = -9.1 ± 0.4 mV), followed by the distal colon (IJPsMAX = -1.8 ± 0.3 mV). A similar rank of order was observed in neural mediated inhibitory mechanical responses including electrical field stimulation-mediated responses and neural tone. ADPßs concentration-response curve was shifted to the left in the distal colon. In contrast, NaNP responses did not differ between regions. Cholinergic neurotransmission elicited contractions of a similar amplitude throughout the colon. CONCLUSION: An inverse gradient of purinergic and nitrergic neurotransmission exists through the mouse colon. The proximal and mid colon have a predominant nitrergic neurotransmission probably due to the fact that their storage function requires sustained relaxations. The distal colon, in contrast, has mainly purinergic neurotransmission responsible for the phasic relaxations needed to propel dehydrated faeces.

Potential role of the gaseous mediator hydrogen sulphide (H2S) in inhibition of human colonic contractility.

BACKGROUND: Hydrogen sulphide (H2S) is an endogenous signalling molecule that might play a physiologically relevant role in gastrointestinal motility. Cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE) are two enzymes responsible for H2S production. d,l-Propargylglycine (PAG) is a CSE inhibitor whereas both aminooxyacetic acid (AOAA) and hydroxylamine (HA) are CBS inhibitors. The characterization of H2S responses and its mechanism of action are crucial to define H2S function. METHODS: Human colonic strips were used to investigate the role of H2S on contractility (muscle bath) and smooth muscle electrophysiology (microelectrodes). NaHS was used as a H2S donor. RESULTS: Combination of PAG and AOAA depolarized the smooth muscle (5-6mV, n=4) and elicited a transient increase in tone (260.5±92.8mg, n=12). No effect was observed on neural mediated inhibitory junction potential or relaxation. In the presence of tetrodotoxin 1µM, NaHS concentration-dependently inhibited spontaneous contractions (EC50=329.2µM, n=18). This effect was partially reduced by the guanylyl cyclase inhibitor ODQ 10µM (EC50=2.6µM, n=12) and by l-NNA 1mM (EC50=1.4mM, n=8). NaHS reversibly blocked neural mediated cholinergic (EC50=2mM) and tachykinergic (EC50=5.7mM) contractions. NaHS concentration-dependently reduced the increase in spontaneous mechanical activity (AUC) induced by carbachol (EC50=1.9mM) and NKA (EC50=1.7mM AUC). CONCLUSIONS: H2S might be an endogenous gasomediator regulating human colonic contractility. Its inhibitory effect is observed at high concentrations and could be mediated by a direct effect on smooth muscle with a possible synergistic effect with NO, as well as by an interaction with the cholinergic and tachykinergic neural mediated pathways.

EP2 and EP4 receptors mediate PGE2 induced relaxation in murine colonic circular muscle: pharmacological characterization.

BACKGROUND: Prostaglandin E2 (PGE2) is a regulator of gastrointestinal motility that might be involved in impaired motor function associated to gut inflammation. The aim of the present work is to pharmacologically characterize responses to exogenous and endogenous PGE2 in the mouse colon targeting EP2 and EP4 receptors. METHODS: Wild type (WT) and EP2 receptor knockout (EP2-KO) mice were used to characterize PGE2 and butaprost (EP2 receptor agonist) effects on smooth muscle resting membrane potential and myogenic contractility in circularly oriented colonic preparations. RESULTS: In WT animals, PGE2 and butaprost concentration-dependently inhibited spontaneous contractions and hyperpolarized smooth muscle cells. Combination of both EP2 (PF-04418948 0.1µM) and EP4 receptor antagonists (L-161,982 10µM) was needed to block both electrical and mechanical PGE2 responses. Butaprost inhibitory responses (both electrical and mechanical) were totally abolished by PF-04418948 0.1µM. In EP2-KO mice, PGE2 (but not butaprost) concentration-dependently inhibited spontaneous contractions and hyperpolarized smooth muscle cells. In EP2-KO mice, PGE2 inhibition of spontaneous contractility and hyperpolarization was fully antagonized by L-161,982 10µM. In WT animals, EP2 and EP4 receptor antagonists caused a smooth muscle depolarization and an increase in spontaneous mechanical activity. CONCLUSIONS: PGE2 responses in murine circular colonic layer are mediated by post-junctional EP2 and EP4 receptors. PF-04418948 and L-161,982 are selective EP2 and EP4 receptor antagonists that inhibit PGE2 responses. These antagonists might be useful pharmacological tools to limit prostaglandin effects associated to dismotility in gut inflammatory processes.

Differential functional role of purinergic and nitrergic inhibitory cotransmitters in human colonic relaxation.

AIM: ATP and nitric oxide (NO) are released from enteric inhibitory motor neurones and are responsible for colonic smooth muscle relaxation. However, how frequency of neural stimulation affects this cotransmission process and the post-junctional responses has not been systematically characterized in the human colon. METHODS: The dynamics of inhibitory cotransmission were studied using different protocols of electrical field stimulation (EFS) to characterize the inhibitory junction potentials (IJP) and the corresponding relaxation in colonic strips obtained from 36 patients. RESULTS: Single pulses elicited a fast IJP (IJPf(MAX) = -27.6 ± 1.6 mV), sensitive to the P2Y1 antagonist MRS2500 1 µm, that ran down with frequency increase leaving a residual hyperpolarization at high frequencies (IJPf∞ = -3.7 ± 0.6 mV). Accordingly, low frequencies of EFS caused purinergic transient relaxations that cannot be maintained at high frequencies. Addition of the P2Y1 agonist MRS2365 10 µm during the purinergic rundown did not cause any hyperpolarization. Protein kinase C (PKC), a putative P2Y1 desensitizator, was able to reduce the amplitude of the IJPf when activated, but the rundown was not modified by PKC inhibitors. Frequencies higher than 0.60 ± 0.15 Hz were needed to evoke a sustained nitrergic hyperpolarization that progressively increased reaching IJPs∞ = -13 ± 0.4 mV at high frequencies and leading to a sustained inhibition of spontaneous motility. CONCLUSION: Changes in frequency of stimulation possibly mimicking neuronal firing will post-junctionally determine purinergic vs. nitrergic responses underlying different functional roles. NO will be responsible for sustained relaxations needed in physiological processes such as storage, while purinergic neurotransmission evoking sharp transient relaxations will be dominant in processes such as propulsion.

Interplay between myogenic pacemakers and enteric neurons determine distinct motor patterns in the rat colon.

Waxing and waning of slow waves amplitude has been recently associated with a segmentation motor pattern in the murine small intestine. The 'wax and wane' phenomenon in this area of the gastrointestinal tract seems to be the result of modulation of slow waves by a second pacemaker of a lower frequency displayed by the interstitial cells of Cajal near the deep muscular plexus (ICC-DMP). In the rat colon, smooth muscle cyclic depolarizations causing low-frequency (LF) contractions (0.9 ± 0.1 cpm) occur together with slow wave activity associated to high-frequency (HF) contractions (14 ± 0.3 cpm; ripples). In the present manuscript, we demonstrate the presence of 'wax and wane' in rat colonic slow waves. Depolarization from the 'wax' to the 'wane' was 7.6 ± 1.2 mV, i.e., smooth muscle cells went from a resting membrane potential (RMP) of -50.0 mV to a RMP of -42.4 mV. The amplitude of the slow wave decreased from 14.0 ± 2.2 mV to 3.4 ± 0.7 mV. The wax and wane phenomenon occurred at 0.9 ± 0.1 cpm, coinciding with the frequency of cyclic depolarizations. Therefore, we hypothesized that the 'wax and wane' of slow waves in the rat colon could be the result of their interaction with the LF pacemaker. We describe three different myogenic motor patterns that depend on the level of smooth muscle and ICC excitation: (i) LF propulsive contractions, (ii) regular slow waves causing ripples, and (iii) a wax and wane pattern that may lead to segmentation. Different intra- and extra-luminal inputs probably determine the dominating motor pattern in each area through the enteric nervous system.

Mechanisms of action of otilonium bromide (OB) in human cultured smooth muscle cells and rat colonic strips.

BACKGROUND: The pharmacological properties of otilonium bromide (OB) have been investigated using different experimental models, techniques, and conditions, and consequently, the results are not always easy to compare. The aim of the present work was to investigate the pharmacological properties of OB in human cultured colonic smooth muscle cells (HCSMCs), which is the main target of the drug 'in vivo'. Rat colonic strips were used to confirm the pharmacological properties. METHODS: Human cultured colonic smooth muscle cells were studied using the calcium imaging technique. Microelectrodes and muscle bath experiments were performed in rat colonic strips. KEY RESULTS: Otilonium bromide (OB) concentration dependently inhibited nifedipine-sensitive calcium transients induced by KCl (EC50  = 3.6 µM) and BayK8644 (EC50  = 4.0 µM). All the following experiments were performed in the presence of nifedipine. In HCSMC, carbachol-induced calcium transients were inhibited by OB (EC50  = 8.4 µM). Carbachol evoked 1-a smooth muscle depolarization (10 mV) that was antagonized by 100 µM OB; and 2-a contraction that was inhibited by OB (EC50  = 13.0 µM). 'Non-nitrergic (L-NNA 1 mM) non-purinergic (MRS2500 1 µM)' conditions were used to elicit endogenous excitatory responses. Electrical field stimulation caused 1-an atropine-sensitive excitatory junction potential that was inhibited by OB (EC50  = 8.9 µM) and 2-an atropine-sensitive contraction that was inhibited by OB (EC50  = 7.3 µM). In HCSMC, neurokinin A (NKA) and CaCl2 induced calcium transients that were inhibited by OB (NKA: EC50  = 11.7 µM; CaCl2 : EC50  = 17.5 µM). CONCLUSIONS & INFERENCES: Otilonium bromide causes inhibition of L-/T-type calcium channels, muscarinic, and tachykininergic responses that acting together explain the pharmacological properties of the compound.

P2Y(1) knockout mice lack purinergic neuromuscular transmission in the antrum and cecum.

BACKGROUND: Pharmacological studies using selective P2Y(1) antagonists, such as MRS2500, and studies with P2Y(1)(-/-) knockout mice have demonstrated that purinergic neuromuscular transmission is mediated by P2Y(1) receptors in the colon. The aim of the present study was to test whether P2Y(1) receptors are involved in purinergic neurotransmission in the antrum and cecum. METHODS: Microelectrode recordings were performed on strips from the antrum and cecum of wild type animals (WT) and P2Y(1)(-/-) mice. KEY RESULTS: In the antrum, no differences in resting membrane potential and slow wave activity were observed between groups. In WT animals, electrical field stimulation elicited a MRS2500-sensitive inhibitory junction potential (IJP). In P2Y(1)(-/-) mice, a nitrergic IJP (N(ω) -nitro-l-arginine-sensitive), but not a purinergic IJP was recorded. This IJP was equivalent to the response obtained in strips from WT animals previously incubated with MRS2500. Similar results were obtained in the cecum: 1- the purinergic IJP (MRS2500-sensitive) recorded in WT animals was absent in P2Y(1)(-/-) mice 2- nitrergic neurotransmission was preserved in both groups. Moreover, 1- spontaneous IJP (MRS2500-sensitive) could be recorded in WT, but not in P2Y(1)(-/-) mice 2- MRS2365 a P2Y(1) agonist caused smooth muscle hyperpolarization in WT, but not in P2Y(1) (-/-) animals, and 3- ß-NAD caused smooth muscle hyperpolarization both in WT and P2Y(1)(-/-) animals. CONCLUSIONS & INFERENCES: 1- P2Y(1) receptor is the general mechanism of purinergic inhibition in the gastrointestinal tract, 2- P2Y(1)(-/-) mouse is a useful animal model to study selective impairment of purinergic neurotransmission and 3- P2Y(1)(-/-) mouse might help in the identification of purinergic neurotransmitter(s).

[Prognostic significance of hemoperitoneum in peritoneal dialysis]. / Significado pronóstico del hemoperitoneo en diálisis peritoneal.

According to previous reviews, hemoperitoneum episodes appear in 6.1-8.4% of the peritoneal dialysis patients, and they are severe in a 20% of them. Due to the absence of severe hemoperitoneum in our peritoneal dialysis program, we retrospectively reviewed hemoperitoneum non-related with abdominal surgery or catheter placing. We analyzed its incidence, etiology, prognostic and clinical outcome, as well as the possible effect of recurrent hemoperitoneum on peritoneal function. A total of 132 patients were treated in our centre during a period of 173 months. Mean age at the beginning of peritoneal dialysis was 59+/-17.1 years, 43.2% were females, and 22.8% of them were menstruating women. Twenty-two patients had at least one hemoperitoneum episode during follow-up, with an incidence of 17%. The mean time interval between the start of peritoneal dialysis and the first hemoperitoneum episode was 0.66+/-0.94 years (range: 0.01-3.20 years). 73% were women. Most cases (59%) were due to menstruation. Remarkably, all the menstruating women presented hemoperitoneum at least once with a high incidence of recurrent episodes. The other hemoperitoneum episodes were mainly of unknown etiology (32% of patients), being this one the main cause in males. We only observed two more cases: a male who presented hemoperitoneum related to dicumarinic overdose and a female who presented hemoperitoneum due to mesenteric ischemia. All the 22 patients had a favourable outcome, except for the woman with mesenteric ischemia, what represented an incidence of 4.5% of severe hemoperitoneum. No significant association was found between episodes of hemoperitoneum and aspirin treatment, dicumarinic treatment or the presence of coagulopathy. There was no association either between recurrent hemoperitoneum and the number of peritonitis episodes, peritoneal function or technique survival. In conclusion, hemoperitoneum is a common and usually benign problem in peritoneal dialysis patients, frequently due to retrograde menstruation, and no deleterious long-term effects were found in patients with recurrent hemoperitoneum.

¿Influye la agitacion intensa del efluente peritoneal para el calculo de la dosis de dialisis en dialisis peritoneal automatica? / Peritoneal fluid agitation and dialysis dose estimation in automatic peritoneal analysis

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Early breastfeeding cessation in rural Senegal: causes, modes, and consequences.

OBJECTIVES: We studied reasons for cessation of breastfeeding before the age of 15 months, replacement feeding modes, and child mortality in West Africa. METHODS: Data were gathered for 12208 children born between 1987 and 1997 in a rural area of Senegal. Interviews were conducted with caregivers of early-weaned children, and child mortality risks were assessed. RESULTS: Fewer than 1% of children had been weaned early. The main reasons for early weaning were maternal death and new pregnancy (in 41% and 27% of cases, respectively). Twenty percent of children had been relactated by a wet nurse, and 16% had received formula. Many early-weaned children died before the age of 2 years (26%), particularly those weaned early as a result of the mother's death (hazard ratio = 5.1; 95% confidence interval [CI] = 1.74, 15.0). Girls had a lower hazard ratio than boys (0.16; 95% CI=0.05, 0.41). CONCLUSIONS: Our results showed that early cessation of breastfeeding was rare but that associated mortality was high, especially when the mother had died.

¿Influye la agitación intensa del efluente peritoneal para el cálculo de la dosis de diálisis en diálisis peritoneal automática? / No disponible

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Confronting and eradicating an epidemic of bacteraemia.

Obtaining vascular access by catheterisation is a good option, especially in patients with vascular system fragility. In the authors' department, there was an increase in Gram Negative Bacillus (GNB) infection in patients with long term catheters (LTC). An objective was set to design an action plan and a new working methodology in order to eradicate the infection and the cause. Three periods were established in the prospective follow-up of LTC patients: the pre-epidemic period (01/94 to 03/99), with a bacteraemia every 144 days per patient, the epidemic period (04/99 to 12/00) with a bacteraemia every ten days per patient, and the post-epidemic period (01/01 to 04/02). A multidisciplinary working group was established, which produced action plans for nursing and technical staff. The working methodology of the service was studied and analysed by means of a review. The deionised water cultures at the entrance to the haemodialysis ward were negative. The dialysis and connector cultures were positive for GNB, confirming that they were of the same genetic origin. An evaluation of the periods was carried out, studying the working methodology, to which no changes were made between the pre-epidemic and epidemic period. In the post-epidemic period, a number of changes were made to the care dynamic, with no other bacteraemia arising to date. Adapting and improving protocols is a good indicator of quality. The role of nursing staff is vital in prevention of GNB.

[An outbreak of gram-negative bacteremia (GNB), especially enterobacter cloacae, in patients with long-term tunnelled haemodialysis catheters]. / Brote epidémico de bacteriemias por bacilos gram-negativos (BGN), especialmente enterobacter cloacae, en una unidad de hemodiálisis, en pacientes portadores de catéteres permanentes tunelizados.

Vascular access through a venous catheter for haemodialysis is associated with increased risk of thrombosis, central venous stenosis, short access survival and inadequate dialysis. The most important catheter-related complications, which determine method survival, are infection and dysfunction. In particular, infectious episodes are in some studies the leading cause for untimely catheter removal and for catheter-related morbidity but also for morbidity in dialysis patients. Double-lumen central venous catheters used for haemodialysis, are common causes of septicaemia. Most cases are caused by staphylococci. Episodes of gram-negative bacteriemia have been traced to bacterial contamination of water and/or dialysate, errors in dialyzer reprocessing, and improper setup procedures. In this paper, we describe and outbreak of gram-negative bacteremia, firstly E. cloacae, in an outpatients haemodialysis unit, in the patients with long-term tunnelled haemodialysis catheters. We describe the epidemic investigation that we achieved to identify the source of contaminating bacteria and the route by which bacteria gained access to the bloodstream. We prove the contamination by gram-negative bacterium of the water-distribution lines and haemodialysis machines. Moreover, E. cloacae strains isolated from the lines and machines are genotypically identical to the isolated from the patients. Also, we prove that the hands of health care personnel are unintentional carriers. The outbreak was finished when decontamination of dialysis machines was enhanced and dialyzer-priming fluid was modified.

Brote epidémico de bacteriemias por bacilos gram-negativos (BGN), especialmente enterobacter cloacae, en una unidad de hemodiálisis, en pacientes portadores de catéteres permanentes tunelizados / An outbreak of Gram-Negative Bacteremia (GNB), especially Enterobacter Cloacae, in patients with long-term tunnelled haemodialysis catheters

Se considera a los catéteres permanentes tunelizados un acceso vascular para hemodiálisis de segundo orden por la morbilidad más elevada que comportan respecto a otros accesos. Las complicaciones son más numerosas, y se relacionan especialmente con la trombosis parcial que origina disfunción en la diálisis, y con las infecciones. Estas últimas pueden originar bacteriemias, mayoritariamente debidas a cocos gram-positivos, estafilococos sobre todo. Las infecciones por bacilos gram-negativos (BGN) son más excepcionales y su origen, aún hoy en día, no está explicado. En las Unidades de Hemodiálisis, se han descrito brotes epidémicos relacionados con la contaminación accidental del agua tratada, del líquido de diálisis o del material accesorio de las máquinas. Describimos un brote epidémico de bacteriemias por BGN, especialmente Enterobacter cloacae, en la Unidad de Hemodiálisis de pacientes crónicos, en enfermos portadores de catéteres permanentes tunelizados. Detallamos minuciosamente los pasos seguidos para intentar descubrir el origen de las bacteriemias, consiguiendo finalmente demostrar la contaminación por BGN de los accesorios de los monitores de hemodiálisis, y el papel humano como vector transmisor involuntario. Establecemos la relación genética entre las cepas de E. cloacae aisladas en los hemocultivos de los pacientes y en los accesorios contaminados de los monitores de hemodiálisis. Tras el aumento de la desinfección de los accesorios de los monitores de diálisis y el cambio en el modo de cebado de los dializadores, se ha conseguido erradicar las bacteriemias por BGN en nuestra Unidad

Vascular access through a venous catheter for haemodialysis is associated with increased rik of thrombosis, central venous stenosis, short access survival and inadequate dialysis. The most important catheter-related complications, which determine method survival, are infection and dysfunction. In particular, infectious episodes are in some studies the leading cause for untimely catheter removal and for catheter-related morbidity but also for morbidity in dialysis patients. Double-lumen central venous catheters used for haemodialysis, are common causes of septicaemia. Most cases are caused by staphylococci. Episodes of gram-negative bacteriemia have been traced to bacterial contamination of water and/or dialysate, errors in dialyzer reprocessing, and improper setup procedures. In this paper, we describe and outbreak of gram-negative bacteremia, firstly E. cloacae, in an outpatients haemodialysis unit, in the patients with long-term tunnelled haemodialysis catheters. We describe the epidemic investigation that we achieved to identify the source of cantaminating bacteria and the route by which bacteria gained access to the bloodstream. We prove the contamination by gramnegative bacterium of the water-distribution lines and haemodialysis machines. Moreover, E. cloacae strains isolated from the lines and machines are genotypically identical to the isolated from the patients. Also, we prove that the hands of health care personnel are unintentional carriers. The outbreak was finished when decontamination of dialysis machines was enhanced and dialyser-priming fluid was modified

Hyperactivity and dopamine D1 receptor activation in mice lacking girk2 channels.

RATIONALE: G-protein-coupled inwardly rectifying potassium channels (GIRKs) regulate synaptic transmission and neuronal firing rates. Co-localization of GIRK2 channels and dopamine receptors in the mesolimbic system suggests a role in regulation of motor activity. OBJECTIVES: To explore the role of GIRK channels in the regulation of motor behavior. METHODS: GIRK2 null mutant mice (knockout) were used. Locomotor activity in a mildly stressful situation was conducted either in a circular open field with video tracking or in standard mouse cages equipped with infrared sensors. Drugs were injected intraperitoneally or subcutaneously. RESULTS: GIRK2 knockout mice demonstrated a transient "hyperactive" behavioral phenotype with initially higher motor activity and slower habituation in a novel situation, increased levels of spontaneous locomotor activity during dark phase in their home cages, and impaired habituation in the open-field test. After habituation, GIRK2 knockout mice showed higher motor activity, which was inhibited by the D(1) receptor antagonist SCH 23390 and was more sensitive to the activating effects of the D(1) receptor partial agonist SKF 38393. In a novel environment (open-field) only the highest dose of SKF 38393 used (20 mg/kg) produced significant activation, perhaps due to a ceiling effect in GIRK2 knockout mice. SCH 23390 inhibited the basal activity levels of mice of both genotypes. CONCLUSIONS: Activation of the dopamine D(1)receptor in a stressful environment may be stronger in GIRK2 deficient mice, and this modified function of D(1) receptors may cause the transient hyperactive behavioral phenotype of these mice.

Nursing protocol for manipulation of haemodialysis catheters.

This study looked at the incidence of infection complications, in relation to central vein catheterisation as a provisional HD access, by means of the establishment of a nursing protocol for the handling of these catheters. Central vein catheterisation is a classical technique in Nephrology.