Nutrient dynamics in wetland systems associated with hydrological and anthropogenic variations in the south of Samborombón Bay, Argentina.

Wetlands provide numerous ecosystem services to the environment, such as nutrient removal and storage. The aim of this work is to evaluate the nutrient dynamics in different sectors within wetland systems in the south of the Samborombón Bay (Argentina) based on hydrological and/or anthropogenic variations. For this purpose, the hydrological features of the wetland were defined through the analysis of satellite images, precipitation and tidal data, and field surveys. Three sectors were identified in the wetland: one with tidal influence, another which is dependent on rainfall, and another that receives inputs from rainfall and from a sewage effluent treatment plant. In order to analyze the nutrient dynamics, samples of surface water, groundwater, and sediments were collected from these sectors. Measurements of pH and electrical conductivity were determined in situ in water samples, while the concentration of inorganic forms of phosphorus and nitrogen, soluble reactive silica, and organic carbon were determined through laboratory analysis. Also, bioavailable phosphorus, organic matter, pH, and electrical conductivity were determined in the sediment samples collected. Statistical analysis of the data reveals differences between the sectors and allows the interpretation of the dynamics of the studied components in the wetland. Electrical conductivity distinguishes the intertidal sectors of the wetland while components associated with P and N discriminate the sectors with inputs from the sewage effluent treatment plant. On the other hand, soluble reactive silica, organic carbon, and organic matter do not seem to be influenced by the tide or effluent discharge. This study demonstrates that the studied wetland works as a nutrient retention area, providing ecosystem services to local inhabitants. Although these services can be utilized, they require a continuous monitoring over time to provide an early warning in case the variations in P and N cycles could lead to eutrophication or wetland degradation.

Assessment of meso- and microplastics distribution in coastal sediments and waters at the middle estuary of the Rio De La Plata, Argentina (SW Atlantic Ocean).

Estuarine coastal water and sediments collected from multiple locations within the middle Río de la Plata (RDLP) estuary were analyzed in order to identify the presence of microplastics (MPs, <5 mm) and mesoplastics (MePs, 5-25 mm) in one of the most significant estuaries in the Southwestern Atlantic. The present study represents one of the first researches to survey MPs and MePs contamination in key stations at RDLP estuary. Average concentrations of 14.17 ± 5.50 MPs/L and 10.00 MePs/L were detected in water samples, while 547.83 ± 620.06 MPs/kg (dry weight) and 74.23 ± 47.29 MePs/kg d.w. were recorded in sediments. The greatest abundances were observed in the more anthropized areas, near urban settlements. Fibers were the most conspicuous plastic items in water and sediments, followed by fragments. On the other hand, surface sediments, and 50 cm and 100 cm-depth sediments also presented MPs and MePs indicating they could serve as a stratigraphic indicator for recently formed sediments. The main polymer type identified were acrylic fibers, followed by polypropylene (PP) and polyethylene terephthalate (PET). Besides, SEM-EDX detected the presence of Si, Fe, Ti, Al and Cl onto the plastics' surface. These elements may serve as additives to enhance the plastics' properties, such as in the case of Ti, or they could originate from the environment, like biogenic Si or Fe, and Al possibly as a component of the suspended particles or sediments adhered to the micro or meso plastics. Finally, the results of the present study showed that MPs and MePs are commonly found in waters and also tend to be trapped in sediments of the RDLP estuary supporting the assertion that these areas play a substantial role in influencing the transport, dispersion, and buildup of MPs in estuarine regions.

Assessment of groundwater-driven dissolved nutrient inputs to coastal wetlands associated with marsh-coastal lagoons systems of the littoral of the outer Río de la Plata estuary.

In coastal wetlands the hydrological dynamics and in particular the groundwater flows play a critical role in the establishment of wetlands and in the transport of salts and nutrients. The aim of the work is to analyze the role that groundwater discharge has in the dynamics of the dissolved nutrients of the wetland associated with the coastal lagoon and marshes of the Punta Rasa Natural Reserve, which is located on the coastal sector of the southern end of the Río de la Plata estuary. A monitoring network in the form of transects was generated in order to define groundwater flows and take samples of dissolved species of N and P. The presence of sandy sediments with similar granulometric profiles in all geomorphological environments determines that the underground flow occurs in a homogeneous aquifer. From the dunes and beach ridges the fresh to brackish groundwater flows with a very low hydraulic gradient towards the marsh and coastal lagoon. The contributions of N and P would derive from the degradation of the organic matter of the environment, in the case of the marsh and coastal lagoon also from the tidal flow and discharge of groundwater, and possibly from atmospheric sources in the case of N. Since in all environments oxidizing conditions dominate, nitrification is the main process which is why the most abundant species of N is the NO3-. Under oxidizing conditions, P has a greater affinity for the sediments in which it is mostly retained, registering it in low concentrations in water. The discharge of groundwater from the dunes and beach ridges provides dissolved nutrients to the marsh and coastal lagoon. However, the low hydraulic gradient and the dominant oxidizing conditions determine that the flow is scarce and that it only acquires relevance in the contribution of NO3-.

A New Potential Resource in the Fight against Candida auris: the Cinnamomum zeylanicum Essential Oil in Synergy with Antifungal Drug.

Candida auris is a multidrug-resistant fungus known to be a global public health problem. The skin-based transmission, together with the marked resistance to drugs, resulted in its rapid spread to all continents. The aim of this study was to identify an essential oil (EO) active in the fight against C. auris. A total of 15 EOs were tested against 10 clinical strains of C. auris. Cinnamomum zeylanicum EO (CZ-EO) was the most effective (MIC90 and MFC90 equal to 0.06% vol/vol). Three fractions obtained from CZ-EO, and the cinnamaldehyde (CIN), the major chemical compound, were tested to identify the principal compound effectives against C. auris. All CIN-containing samples showed anti-fungal activity. To study the synergy with fluconazole, CZ-EO, its active fraction (FR2), and CIN were tested in checkerboard tests. Results show that CZ-EO and FR2, but not CIN, synergize with fluconazole. Furthermore, only the copresence of CZ-EO or FR2 synergize with fluconazole at therapeutic concentrations of the drug (0.45 ± 0.32 µg/mL and 0.64 ± 0.67 µg/mL, respectively), while CIN only shows additive activity. In vivo studies conducted on Galleria mellonella larvae show the absence of toxicity of CZ-EO up to concentrations of 16% vol/vol, and the ability of CZ-EO to reactivate the efficacy of fluconazole when formulated at synergic concentrations. Finally, biochemical tests were made to study the mechanism of action of CZ-EO. These studies show that in the presence of both fluconazole and CZ-EO, the activity of fungal ATPases decreases and, at the same time, the amount of intracellular drug increases. IMPORTANCE This study highlights how small doses of CZ-EO are able to inhibit the secretion of fluconazole and promote its accumulation in the fungal cell. In this manner, the drug is able to exert its pharmacological effects bypassing the resistance of the yeast. If further studies will confirm this synergy, it will be possible to develop new therapeutic formulations active in the fight against C. auris resistances.

Enhanced activity of a hydrogen sulphide-releasing derivative of mesalamine (ATB-429) in a mouse model of colitis.

BACKGROUND AND PURPOSE: Mesalamine is the first-line therapy for colitis, but it lacks potency and is only effective for mild-to-moderate forms of this disease. Hydrogen sulphide has been shown to be a potent, endogenous anti-inflammatory substance, modulating leukocyte-endothelial adhesion and leukocyte migration. The purpose of this study was to determine if an H(2)S-releasing derivative of mesalamine (ATB-429) would exhibit increased potency and effectiveness in a mouse model of colitis. EXPERIMENTAL APPROACH: Colitis was induced in mice with trinitrobenzene sulphonic acid and the effects of ATB-429 and mesalamine were compared in several treatment regimens. The severity of colitis was determined using several indices, including a disease activity score (comprised of scores for diarrhea, weight loss and fecal blood), colonic myeloperoxidase activity and macroscopic/microscopic scoring of tissue injury. KEY RESULTS: Irrespective of the treatment regiment, ATB-429 was more effective than mesalamine in reducing the severity of colitis. ATB-429 was particularly effective in reducing granulocyte infiltration into the colonic tissue (by approximately 70%), as well as reducing the expression of mRNA for several key proinflammatory cytokines/chemokines (e.g., TNFalpha, IFNgamma). Treatment with ADT-OH, the H(2)S-releasing moiety of ATB-429, did not affect severity of colitis. CONCLUSIONS AND IMPLICATIONS: ATB-429 exhibits a marked increase in anti-inflammatory activity and potency in a murine model of colitis, as compared to mesalamine. These results are consistent with recently described anti-inflammatory effects of H(2)S. ATB-429 may represent an attractive alternative to mesalamine for the treatment of inflammatory bowel disease.

NSAIDs, coxibs, CINOD and H2S-releasing NSAIDs: what lies beyond the horizon.

Nonsteroidal anti-inflammatory drugs are widely prescribed for treatment of pain and inflammation, despite their association with gastrointestinal complications, including bleeding and perforation. Inhibition of cyclo-oxygenases, is the main mechanism of action of aspirin and nonsteroidal anti-inflammatory drugs. Non-selective nonsteroidal anti-inflammatory drugs inhibit cyclo-oxygenase-1 and cyclo-oxygenase-2. Inhibition of cyclo-oxygenase-1 derived prostanoids in the stomach represent the underlying mechanism involved in development of gastric and duodenal ulcers in patients taking nonsteroidal anti-inflammatory drugs. Selective cyclo-oxygenases-2 inhibitor (coxibs) spare cyclo-oxygenase-1 show enhanced safety profile in the gastrointestinal tract, but increase the risk of heart attack and stroke. Spurred by these findings, two coxibs, rofecoxib and valdecoxib, were withdrawn from the market. In addition to prostanoids, two gaseous mediators, nitric oxide (NO) and hydrogen sulfide (H(2)S) exert protective effects in gastric mucosa. The inhibitory effects of NO on nonsteroidal anti-inflammatory drugs-induced leukocyte adherence have been exploited in the development of NO-releasing nonsteroidal anti-inflammatory drugs, also indicated as cyclo-oxygenase-inhibiting NO-donating drugs. Despite its non-selective profile versus cyclo-oxygenase isoenzymes, naprocyclo-oxygenase-inhibiting NO-donating drugs, the prototype of this class of anti-inflammatory agents, reduces systemic blood pressure and might have enhanced cardiovascular safety than coxibs, while causing less gastrointestinal damage than its parent drug, the naproxen. H(2)S-releasing nonsteroidal anti-inflammatory drugs derivatives have been recently developed, based on the observed ability of this gaseous mediator to cause vasodilation and to prevent leukocyte adherence. In pre-clinical settings, H(2)S-releasing nonsteroidal anti-inflammatory drugs produce less gastric damage as compared to the parent drugs. Cyclo-oxygenases-inhibiting NO-donating drugs and H(2)S-releasing nonsteroidal anti-inflammatory drugs represent examples of new anti-inflammatory drugs created through the exploitation of the beneficial effects of endogenous gaseous mediators in the gastrointestinal and cardiovascular systems.

Hydrogeochemical and isotopic signature of surface and groundwater in a highly industrialized sector of the Rio de la Plata coastal plain (Argentina).

The coastal plain of the middle estuary of the Río de la Plata is a highly industrialized area and is densely populated by sectors. The main human activity in the sector encompassed between the cities of Ensenada and Berisso is associated with the petrochemical industry. In this work, hydrogeochemical and isotopic characteristics of surface and groundwater in the impacted area are analyzed and the results are contrasted with those obtained in an undisturbed protected area. Major and trace elements were determined using standardized methods while the stable isotopes δ18O y δ2H were analyzed by mass spectroscopy. Human impact is evidenced by the occurrence of large variations in the major chemical composition of water, and also by the elevated concentrations of some trace elements that are not contributed from natural sources. These results may contribute to the understanding of chemical processes and pollutants distribution in highly industrialized coastal plain areas.

Sports Eligibility After Risk Assessment and Treatment in Children with Asymptomatic Ventricular Pre-excitation.

BACKGROUND AND OBJECTIVE: Many studies concern the management of young patients with symptomatic Wolff-Parkinson-White (WPW) syndrome, but little information exists on the significance and prognosis of ventricular pre-excitation (VPE) in asymptomatic children. The aim of the study was to evaluate the risk of sudden death in young athletes with asymptomatic VPE by transesophageal electrophysiological study (TEEPS) and their sports eligibility after the risk assessment and/or ablative treatment. METHODS: Ninety-one asymptomatic children and adolescents underwent TEEPS both at rest and during adrenergic stress (exercise testing or isoproterenol infusion). After electrophysiological testing, patients were assessed in the 36 months of follow-up. RESULTS: Thirty-three patients (36.3 %) had a benign form of VPE and were allowed to participate in competitions. Ten patients (11 %) were at borderline risk; thus, sport eligibility was evaluated individually. Forty-eight patients (52.7 %) showed inducible sustained atrioventricular reentrant tachycardia and/or atrial fibrillation (AF), 11 of whom (12.1 % of total population) had a potential risk of sudden cardiac death due to AF inducibility during physical stress. Forty-five young athletes underwent transcatheter ablation (TCA). TCA was interrupted in 12 patients (26.7 %) because of the high procedural risk linked to septal accessory pathway (AP) location. There were no TCA-related complications, and all patients remained asymptomatic during follow-up. CONCLUSION: Most of the young athletes with asymptomatic VPE may be allowed to participate in competitive sports after an adequate risk assessment and/or ablative treatment. However, in our opinion, special care should be taken to avoid procedural complications, which are unacceptable in asymptomatic patients.

NO-naproxen modulates inflammation, nociception and downregulates T cell response in rat Freund's adjuvant arthritis.

1. Anti-inflammatory non steroidal drugs releasing NO (NO-NSAIDs) are a new class of anti-inflammatory drugs to which has been added an NO-releasing moiety. These compounds have been shown to retain the anti-inflammatory, analgesic and antipyretic activity of the parent compound but to be devoid of gastrointestinal (GI) toxicity. 2. Freund's adjuvant (FA) arthritis was induced in rats by a single intraplantar injection into the right hindpaw of 100 microl of mycobacterium butirricum (6 mg ml(-1)). The effect of equimolar doses of naproxen (1, 3 and 10 mg kg(-1)) and NO-naproxen (1.5, 4.5 and 16 mg kg(-1)) was evaluated using two dosage regimen protocols: (i) preventive, starting oral administration of the drugs at the time of induction of arthritis and for the following 21 days (day 1 - 21); (ii) therapeutic, starting oral administration of the drugs 7 days after adjuvant injection and for the following 14 days (day 7 - 21). 3. Hindpaw swelling (days 3, 7, 11, 14, 17, 21) and nociception (days 15 and 21) were measured. On day 22 rats were sacrificed, draining lymph nodes were removed and T cells isolated. In vitro proliferation of T cells following stimulation with concanavalin A (0.5 - 5 microg ml(-1)) was measured using a tritiated thymidine incorporation assay. IL-2 receptor expression on T cells was measured by FACS analysis. 4. Naproxen and NO-naproxen showed similar activity in reducing oedema formation in the non-injected (controlateral) hindpaw. Both drugs showed anti-nociceptive effect. NO-naproxen was anti-nociceptive at a dose of 4.5 mg kg(-1) while naproxen showed the same extent of inhibition only at a dose of 10 mg kg(-1). 5. T cells were isolated and characterized by FACS analysis. Stimulation of isolated T cells with concanavallin A in vitro caused a significant increase in thymidine uptake. NO-naproxen at a dose of 4.5 mg kg(-1) inhibited T cell proliferation to the same extent as 10 mg kg(-1) of naproxen. 6. Inhibition of T cell proliferation was well correlated with reduced IL-2 receptor expression on T cells. In addition, NO-naproxen reduced both IL-1beta and TNFalpha plasma levels whilst naproxen reduced IL-1beta levels only. 7. In conclusion, both naproxen and NO-naproxen reduce inflammation and nociception associated with arthritis. In addition NO-naproxen interferes to a larger extent with cellular mechanism involved in T cell activation in rat adjuvant arthritis indicating that introduction of the NO moiety in the naproxen structure increases the effect at the level of the immune system.

TNFalpha processing enzyme inhibitors prevent aspirin-induced TNFalpha release and protect against gastric mucosal injury in rats.

BACKGROUND: Although previous studies indicate that prevention of tumour necrosis factor alpha (TNFalpha) release protects against NSAID-induced gastric mucosal injury, intracellular pathways by which aspirin causes TNFalpha release are unknown. TNFalpha is synthesized as a precursor which is proteolytically cleaved by a specific converting enzyme, TACE, to release the mature cytokine. TACE inhibitors prevent TNFalpha release and protect against TNFalpha-mediated disease. AIM: To investigate: (i) molecular events that regulate TNFalpha secretion in response to aspirin in vivo and in vitro; (ii) whether TNFalpha secretion inhibitors prevent aspirin-induced TNFalpha release and protect against gastric mucosal damage; and (iii) whether TNFalpha exerts a direct cytotoxic effect on gastric epithelial cells. METHODS: In vitro studies were carried out on mouse macrophages and rat gastric mucosal cells. Gastric mucosal damage was induced in rats by oral administration of 300 mg/kg aspirin. TNFalpha cytotoxicity on gastric mucosal cells was examined by treating rats with lipopolysaccharide to release TNFalpha or by incubating dispersed gastric mucosal cells with increasing concentrations of TNFalpha. RESULTS: Aspirin increases intracellular calcium (Ca2+) levels and causes a time and concentration dependent increase in macrophage TNFalpha mRNA accumulation and cytokine release. Agents that cause Ca2+ mobilization with a receptor-independent mechanism, such as ionomycin and thapsigargin, stimulate TNFalpha release. Incubating the macrophages in a Ca2+ free medium inhibited TNFalpha secretion. Agents that prevent TNFalpha mRNA transcription, e.g. lisophylline, PGE2, interleukin-10 and 8-BrcAMP, or TACE inhibitors, e.g. EDTA, TAPI-2 and BB-3103, inhibit TNFalpha release and protect rats against gastric mucosal injury induced by oral administration of aspirin. TNFalpha exerts a direct cytotoxic effect on gastric epithelial cells as demonstrated by the reduced viability observed in gastric mucosal cells prepared from rats treated with lipopolysaccharide, or directly incubated with increasing concentrations of TNFalpha. CONCLUSIONS: (i) Aspirin directly stimulates TNFalpha gene transcription; (ii) TACE inhibitors protect against aspirin-induced gastric mucosal injury; and (iii) TNFalpha exerts a direct cytotoxic effect on gastric epithelial cells.

NSAIDs upregulate beta 2-integrin expression on human neutrophils through a calcium-dependent pathway.

BACKGROUND: Margination of circulating neutrophils (PMN) into the gastric microcirculation is an early and critical event in the pathogenesis of non-steroidal antinflammatory drug (NSAID)-induced gastropathy. This effect is mediated through the upregulation of beta 2 integrins on the PMN surface. AIMS: To investigate whether indomethacin modulates: (1) Mac-1 expression; (2) Ca2+ mobilization ([Ca2+]i), protein kinase C and nitric oxide accumulation; and (3) mitogen-associated protein kinase phosphorylation in human PMN. METHODS: Human PMN were isolated by centrifugation through a double Ficoll gradient. [Ca2+]i was measured in PMN loaded with fura-2 and Mac-1 expression by flow cytometry. RESULTS: Indomethacin caused a concentration- and time-dependent upregulation of CD11b and CD18 expression and PMN adhesion to endothelial cells. Maximal upregulation of Mac-1 expression (40-50%) occurred after a 30-min incubation with 0.1mM indomethacin. The effect was prevented by removing the Ca2+. Ionomycin and thapsigargin caused a 7-10-fold increase in [Ca2+]i and a 2-4-fold increase in Mac-1 expression. Indomethacin induced a concentration-dependent phosphorylation of a 41-kDa mitogen-associated protein kinase. Tyrosine kinase inhibitors prevented the effect of indomethacin on Mac-1 expression and Ca2+ mobilization. Indomethacin and ionomycin increased superoxide generation, myeloperoxidase secretion and PMN adherence to endothelial cells and stimulated nitric oxide production. Indomethacin-induced Mac-1 upregulation was prevented by a nitric oxide synthase inhibitor. CONCLUSIONS: Indomethacin-induced upregulation of Mac-1 is mediated by changes in [Ca2+]i and nitric oxide. Phosphorylation of the 41-kDa mitogen-associated protein isoform is a previously unreported target of NSAID action. These effects might help to explain the ability of indomethacin to cause gastric neutrophil margination.

Nitric oxide-releasing NSAIDs inhibit interleukin-1beta converting enzyme-like cysteine proteases and protect endothelial cells from apoptosis induced by TNFalpha.

BACKGROUND: Nitric oxide (NO)-releasing NSAIDs are a new class of NSAID derivatives with markedly reduced gastrointestinal toxicity. Although it has been demonstrated that NO-NSAIDs spare gastric mucosal blood flow, molecular determinants involved in this effect are unknown. AIM: To investigate the effect of aspirin, naproxen and flurbiprofen, and their NO-derivatives, on gastric apoptosis and endothelial cell damage induced by tumour necrosis factor-alpha (TNFalpha). In other systems, TNFalpha-induced apoptosis is mediated by caspases, a growing family of cysteine proteases similar to the IL-1beta converting enzyme (ICE), and so we have investigated whether NO-NSAIDs modulate ICE-like endopeptidases. METHODS: Rats were treated orally with aspirin, naproxen and flurbiprofen, or their NO-releasing derivatives in equimolar doses, and were killed 3 h later to assess mucosal damage and caspase activity. Endothelial cells (HUVECs) were obtained from human umbilical cord by enzymatic digestion. Caspase 1 and 3 activities were measured by a fluorimetric assay using selective peptides as substrates and inhibitors. Apoptosis was quantified by ELISA specific for histone-associated DNA fragments and by the terminal transferase nick-end translation method (TUNEL). RESULTS: In vivo NSAID administration caused a time-dependent increase in gastric mucosal damage and caspase activity. NCX-4016, NO-naproxen and NO-flurbiprofen did not cause any mucosal damage and prevented cysteine protease activation. NSAIDs and NO-NSAIDs stimulated TNFalpha release. Exposure to TNFalpha resulted in a time- and concentration-dependent HUVEC apoptosis, an effect that was prevented by pretreating the cells with NCX-4016, NO-naproxen, NO-flurbiprofen, SNP or Z-VAD.FMK, a pan-caspase inhibitor. The activation of ICE-like cysteine proteases was required to mediate TNFalpha-induced apoptosis of HUVECs. Exogenous NO donors inhibited TNFalpha-induced cysteine protease activation. Inhibition of caspase activity was due to S-nitrosylation of ICE/CPP32-like proteases. NO-NSAIDs prevented IL-1beta release from endotoxin-stimulated macrophages. CONCLUSIONS: NO-releasing NSAIDs are a new class of non-peptide caspase inhibitors. Inhibition of ICE-like cysteine proteases prevents endothelial cell damage induced by pro-inflammatory agents and might contribute to the gastro-protective effects of NO-NSAIDs.

Effects of early protein malnutrition and environmental stimulation upon the reactivity to diazepam in two animal models of anxiety.

In order to investigate the effects of early protein malnutrition and environmental stimulation upon the response to the anxiolytic properties of diazepam, two animal models of anxiety (elevated plus-maze and light-dark transition tests) were used. Rats were malnourished by feeding their dams a 6% protein diet during the lactation period (0-21 days of age) while well-nourished controls received a 16% protein diet. From 21 to 70 days of age all rats received a balanced lab chow diet. Environmental stimulation consisted of 3-min daily handling from birth to 70 days of age. Additional stimulation was provided from 21 to 70 days of age by rearing the rats in an enriched living cage. Eight groups of rats were studied in a 2 (malnourished or well-nourished) x 2 (stimulated or nonstimulated) x 2 (diazepam or vehicle) design. At 70 days of age, independent groups of rats treated with diazepam (2.5 mg/kg, IP) or vehicle were submitted to testing in the elevated plus-maze or light-dark transition procedures. The results showed that both diazepam and environmental stimulation reduced anxiety in the elevated plus-maze; stimulation changed the anxiolytic response to diazepam and the two diet conditions altered differentially the response to both pharmacological and stimulation procedures. These results suggest that environmental stimulation can affect differentially the behavioral response of malnourished and well-nourished rats treated with diazepam.

Ethanol, a Leydig cell toxin: evidence obtained in vivo and in vitro.

The available evidence which suggests that ethanol is a Leydig cell toxin is presented. Both in vivo and in vitro data are reviewed. The minor differences obtained in vitro as compared to those obtained in vivo are discussed. As a result of information obtained during the last decade, there can be little doubt that ethanol and possibly acetaldehyde are clinically important environmental Leydig cell toxins.

Endoscopic treatment of bile duct stones.

Approximately fifteen per cent of patients who undergo gallstones also have concomitant common bile duct stones. Endoscopic papillosphincterotomy (EPS) is the treatment of choice for common bile duct stones in cholecystectomized patients as well as in patients with gallbladder in situ but at high operative risk. Endoscopic papillosphincterotomy is a highly effective technique and able to remove stones from choledochus in 85-90% of cases. The failure of EPS is mainly related to the size of stones (greater than 15 mm). However, recently introduced sophisticated techniques, such as extraluminal (extracorporeal shock wave lithotripsy) or intraluminal lithotripsy (mechanical, electro-hydraulical or laser) now allow to fragment and remove also "large" stones. Should EPS fail to remove stones, a naso-biliary tube can be endoscopically positioned and attempts made to dissolve the stone by infusing chemical solvents. However, until now the chemical dissolution has only a marginal efficacy in the treatment of common bile duct stones. If all these techniques fail, good operative risk patients can be treated by surgical choledochotomy, while high operative risk patients can be treated by permanent biliary endoprosthesis or percutaneous techniques.

Non-invasive hemodynamic analysis in cardiac resynchronization therapy patients wearing quadripolar left ventricular leads: the importance of pacing electrode selection.

AIM: Quadripolar left ventricular (LV) leads offer multiple choices for LV pacing increasing programming flexibility. Aim of this study is to assess the influence of LV pacing vector selection on hemodynamic parameters for patients who underwent cardiac resynchronization therapy (CRT) using quadripolar LV lead chronically evaluated with a non-invasive approach by Nexfin(®) system provided analysis (BMEYE B.V., Amsterdam, The Netherlands). METHODS AND RESULTS: In 16 CRT patients implanted with a quadripolar LV lead (mean follow-up 8,8 ±13,4 months after implantation), we measured Cardiac Output (CO), Mean Blood Pressure (MBP), Total Peripheral Resistance (TPR), LV dP/dt max and Stroke volume (SV) from each one of the ten available bipolar pacing configurations. All the recorded parameters showed marked differences among the ten pacing configurations, but dP/dt max, SV and TPR were those showing the wider range, depending of the selected pacing vector. The average delta for the whole group of subjects between the maximum and minimum hemodynamic values for each pacing configuration were 15.9% for SV, 21.1% for dP/dt max and 20.3% for TPR. Inter-individual analysis of data failed to identify a link between a specific pacing vector and the hemodynamic response. CONCLUSION: Our study demonstrates that different bipolar pacing configurations, even if arising from a single CS branch, substantially modify the hemodynamic effect of LV pacing in CRT patients. Moreover, the non-invasive hemodynamic analysis suggests the better pacing configuration should be established individually and could represent an important issue in optimizing CRT during follow-up.