Biochemical characteristics and modulation by external and internal factors of aminopeptidase-N activity in the hepatopancreas of a euryhaline burrowing crab.

Strikingly, in spite of its physiological importance, information about occurrence, biochemical characteristics and mechanisms of regulation of aminopeptidase-N (APN) in the hepatopancreas of intertidal euryhaline crabs is still lacking. In this work, we determined the occurrence, biochemical characteristics, response to environmental salinity and dopamine of APN in the hepatopancreas of the euryhaline crab Neohelice granulata (Dana 1851) from the open mudflat of Mar Chiquita coastal lagoon (Buenos Aires province, Argentina). APN activity was maximal at pH and temperature range of 7.6-9.0 and 37-45 °C, respectively. APN activity exhibited Michaelis-Menten kinetics (apparent Km = 0.19 ± 0.10 mM) (pH 7.6, 37 °C) and appeared to be sensitive to bestatin (I 50 = 15 mM) and EDTA (I 50 = 9 mM). In crabs acclimated to 10 psu (hyper-regulation conditions) and 37 psu (hypo-regulation conditions), APN activity was about 45 and 160% higher, respectively, than in 35 psu (osmoconformation). APN activity in the hepatopancreas was stimulated in vitro (about 137%) by 10(-4) M dopamine. Higher dopamine concentrations produced a similar extent of increase. The responses of APN activity to salinity and dopamine in vitro suggest the role of APN in digestive adjustments upon hyper and hypo-regulatory conditions and its modulation via direct mechanisms on hepatopancreas by dopamine.

The environmental sustainability of microalgae as feed for aquaculture: a life cycle perspective.

The environmental sustainability of microalgae production for aquaculture purposes was analyzed using exergy analysis (EA) and life cycle assessment (LCA). A production process (pilot 2012, 240 m(2)) was assessed and compared with two upscaling scenarios (pilot 2013, 1320 m(2) and first production scale 2015, 2.5 ha). The EA at process level revealed that drying and cultivation had the lowest efficiencies. The LCA showed an improvement in resource efficiency after upscaling: 55.5 MJ(ex,CEENE)/MJ(ex) DW biomass was extracted from nature in 2012, which was reduced to 21.6 and 2.46 MJ(ex,CEENE)/MJ(ex) DW in the hypothetical 2013 and 2015 scenarios, respectively. Upscaling caused the carbon footprint to decline by factor 20 (0.09 kg CO2,eq/MJ(ex) DW in 2015). In the upscaling scenarios, microalgae production for aquaculture purposes appeared to be more sustainable in resource use than a reference fish feed (7.70 MJ(ex,CEENE) and 0.05 kg CO2,eq per MJ(ex) DW).

Randomized clinical trial of mesh fixation with "double crown" versus "sutures and tackers" in laparoscopic ventral hernia repair.

BACKGROUND: Although laparoscopic intra-peritoneal mesh repair (LVHR) is a well-established treatment option to repair ventral and incisional hernias, no consensus in the literature can be found on the best method of fixation of the mesh to the abdominal wall. METHODS: Between December 2004 and July 2008, 76 patients undergoing a LVHR were randomized between mesh fixation using a double row of spiral tackers (DC) (n = 33) and mesh fixation with transfascial sutures combined with one row of spiral tackers (S&T) (n = 43), in the WoW trial (with or without sutures). Patients were clinically examined and evaluated using a visual analog scale for pain (VAS) in rest and after coughing 4 h post-operatively, after 4 weeks and 3 months after surgery. Primary endpoint of the study was abdominal wall pain, defined as a VAS score of at least 1.0 cm, at 3 months post-operative. Quality of life was quantified with the SF-36 questionnaire preoperatively and after 3 months. Secondary endpoint was the recurrence rate at 24-month follow-up. RESULTS: The DC and S&T group were comparable in age, gender, ASA score, BMI, indication, hernia, and mesh variables. The DC group had a significant shorter operating time compared with the S&T group (74 vs 96 min; p = 0.014) and a significant lower mean VAS score 4 h post-operatively (in rest; p = 0.028/coughing; p = 0.013). At 3 months, there were significant more patients in the S&T group with VAS score ≥1.0 cm (31.4 vs 8.3 %; p = 0.036). Clinical follow-up at 24 months was obtained in 63 patients (82.9 %). The recurrence rate at 24 months was 7.9 % overall (5/63). There were more recurrences in the S&T group (4/36) than in the DC group (1/27), but this difference was not significant (11.1 vs 3.7 %; p = 0.381). CONCLUSION: We found that double-crown fixation of intra-peritoneal mesh during laparoscopic ventral hernia repair was quicker, was less painful immediately post-operative and after 3 months, and did not increase the recurrence rate at 24 months. In hernias at a distance from the bony borders of the abdomen, transfascial sutures can be omitted if a double crown of tackers is placed.

Perioperative outcomes of revisional laparoscopic gastric bypass after failed adjustable gastric banding and after vertical banded gastroplasty: experience with 107 cases and subgroup analysis.

BACKGROUND: A growing number of revision procedures are to be expected in bariatric surgery after failed restrictive procedures such as failed adjustable gastric banding (AGB) or vertical banded gastroplasty (VBG). Conversion to revisional laparoscopic Roux-en-Y gastric bypass (ReLRYGBP) has been advocated as the procedure of choice. METHODS: The results of ReLRYGBP were reviewed in a retrospective chart review. A subgroup analysis compared perioperative results after VBG and after AGB. A second subgroup analysis compared perioperative results of ReLRYGBP immediately after AGB removal and after a delay as a two-step procedure. RESULTS: Between 2003 and 2009, ReLRYGBP was performed for 107 patients. Of these 107 operations, 21 were performed after failed VBG and 86 after failed AGB. The mean body mass index (BMI) was 42 kg/m(2). The causes of failure were mainly insufficient weight loss or reflux disease-related symptoms. During a median follow-up period of 44 months, there was no mortality, and morbidity was 34 %, including late complications. Major early complications occurred in 11 % of the cases (n = 12). Conversions and major early complications occurred significantly more frequently after VBG than after AGB (p < 0.05). In 59 % of the cases (n = 50), ReLRYGBP was performed as a single-stage procedure immediately after removal of AGB and in 41 % of the cases (n = 36) as a delayed two-step procedure. The outcomes did not differ significantly (p > 0.5). CONCLUSIONS: The perioperative outcomes of ReLRYGBP are worse after VBG than after AGB. The ReLRYGBP operation can be performed safely as a one-step procedure after AGB removal.

Selection of human immunodeficiency virus type 1 resistance against the pyranodipyrimidine V-165 points to a multimodal mechanism of action.

OBJECTIVES: We have previously identified the pyranodipyrimidines (PDPs) as a new class of integrase (IN) inhibitors. The most potent congener V-165 inhibits HIV-1 integration at low micromolar concentrations by inhibiting the binding of IN to the DNA. As part of pre-clinical studies with PDP, we wanted to investigate HIV resistance development against V-165 and to further characterize the physicochemical properties of the compound. METHODS: We selected PDP-resistant HIV-1 strains by growing the virus in the presence of increasing concentrations of V-165. The selected strains were analysed genotypically and phenotypically. Mutant IN enzymes were generated and evaluated in an enzymatic oligonucleotide-based assay for their activity and sensitivity to the different IN inhibitors. In addition, the antiviral effect of the compound on viral entry and integration was measured using quantitative PCR. RESULTS: Numerous mutations were detected in the RT, IN and env genes of the virus selected in the presence of V-165. Although V-165 inhibited integration in vivo as indicated by a decrease in the number of integrated proviruses, the compound also inhibited viral entry at a concentration of 19 microM. V-165 was poorly recovered from human hepatic microsomal matrix and 1% BSA. CONCLUSIONS: These data point to a multimodal mechanism of action. A quest for derivatives of V-165 that specifically target IN should be pursued.

A 2-year outcome audit of a versatile orthodontic bone anchor.

This study examined complications leading to, or possibly leading to, treatment failure, related to the use of the orthodontic bone anchor (OBA). The OBA is a potential means of providing absolute anchorage and consists of a base-plate fixed with mono-cortical screws, a neck piercing the soft tissues, and a coronal part with conventional orthodontic hooks, tubes or slots. The investigation took the form of a single centre prospective registry at a supra-regional teaching hospital. Eighteen patients (average age 21 years) had one to four OBAs placed between January 2000 and February 2002. Altogether 35 OBAs were placed. Follow-up took place until April 2004. Reasons for placing the OBAs were noted together with any associated complications during the follow-up period. Twenty-three OBAs have been removed so far, four prematurely (one of them before it was taken into use, due to a change of treatment plan enforced by loss of the contralateral OBA). Nineteen were removed as planned after completion of the intended tooth movements. Common (but minor) complications included granulations, acute gingivitis and gingival recession. Light mobility of the OBA was also noted in some cases, but without clinical repercussions. The OBA can be loaded directly, at the level of the orthodontic archwire or more occlusally. It can be placed at any site at the circumference of the jaws, given good quality and thickness of the bony wall. Conventional biomechanical techniques can be applied. However, the failure rate (premature loss of OBA) of 8.6% is considered high, and has necessitated changes in the hardware and protocol.

Optimized lentiviral vector production and purification procedure prevents immune response after transduction of mouse brain.

HIV-derived lentiviral vectors are efficient vehicula to deliver genes into the brain and hold great promise for future gene therapy of neurodegenerative disorders. However, administration of the current vector preparations in mouse brain was found to induce a systemic immune response to vector proteins and a modest inflammation in the brain. Moreover, serum antibodies from vector-treated animals were capable of partially neutralizing lentiviral vector-mediated transduction in cell culture. To avoid this unexpected immune reaction, we have optimized new vector production and purification protocols. Purification by sucrose gradient ultracentrifugation abolished the immune response, but vector titers also decreased substantially. Lentiviral vector production in the absence of serum in the cell culture medium equally reduced immunogenicity without affecting transduction efficiency. These results have important implications for future clinical use of lentiviral vectors, and for the use of lentiviral vectors to create animal models for neurodegenerative diseases that have an important neuroinflammatory component.

Gastric emptying in cats using foods varying in fiber content and kibble shapes.

The purpose of this study is to evaluate the influence of kibble shape and fiber content of commercial dry foods on gastric emptying in healthy cats. Eight healthy cats were used to evaluate four different diets which varied in shape of kibble (round versus triangle) or fiber content (low versus high). Diets were labeled with 99mTc-mebrofenin and gastric emptying was evaluated with nuclear scintigraphy. There was a significant difference between the kibble shapes at both T50 and T20. The triangle shaped kibble required significantly longer time than the round kibble to reach T50 (P = 0.02) and T20 (P = 0.001). Diet fiber content did not have a significant influence on T50, and T20. The influence of caloric and water intake was assessed with division of cats into high, medium, and low intake groups. The caloric intake had its main effect at T50 with the lowest quartile of caloric intake requiring significantly less time to reach T50 than the middle group and upper quartile (P = 0.05). Water intake did not have a significant effect on gastric emptying in this study. There was no relationship or correlation between the surface area of the food (cm2/kg) and T90, T50, and T20.

Carcinogenic effects of hyperthermia.

The purpose of this paper is to assess the evidence for and against the premise that hyperthermia is carcinogenic. The paper is one of several published in this issue of the International Journal of Hyperthermia on the subject of the health risks of hyperthermia. The motivation for this issue of the journal was the result of a World Health Organization workshop that dealt with this issue, as it relates to exposure of the population to RF fields. Since hyperthermia can be a natural consequence of such exposures, the health risks of hyperthermia are relevant in this context. Particularly in the case of carcinogenesis, it is necessary to provide a brief overview of the data that have been generated to examine the carcinogenic risks of RF exposure, so that these results can be compared with studies that have examined the carcinogenic risks of hyperthermia. For this reason, the paper is organized into three sections dealing with: (1) effects of heat on DNA damage/repair and mutations, (2) in vivo studies evaluating the carcinogenic potential of heat alone and combined with other carcinogens, and (3) in vivo studies involving RF exposures. The bulk of the data presented indicate that hyperthermia alone is not carcinogenic. If hyperthermia occurs in the presence of exposure to known carcinogens, such as radiation or chemical carcinogens there is the potential for modulation of carcinogenic effects of those agents. In some circumstances, hyperthermia can actually protect against tumour formation. In other instances, hyperthermia clearly increases incidence of tumour formation, but this occurs following thermal exposures (several degrees C temperature rise for up to 1 h or more) and radiation (therapeutic levels as for treatment of cancer) or chemical carcinogen doses higher than would be encountered by the general population. The extrapolation of these results to the general population, where radiation exposure levels would be at background and temperature rise from incidental RF exposure, such as cell phones (which are estimated to cause no more than 0.1 degrees C temperature rise) is not recommended. Current evidence indicates that the temperature elevations resulting from RF exposure are not carcinogenic. Caution should be used in situations where exposure to known carcinogens is combined with thermal exposures high enough to cause tissue damage. A summary of thermal thresholds for tissue damage from hyperthermia is presented in another paper in this special issue (Dewhirst et al.). No data exist that examine the carcinogenic risks of chronic thermal exposures below the threshold for detectable tissue damage, either alone or in combination with known carcinogens. This is an important goal for future research.

Basic principles of thermal dosimetry and thermal thresholds for tissue damage from hyperthermia.

This paper is one of several in this Special Issue of the International Journal of Hyperthermia that discusses the current state of knowledge about the human health risks of hyperthermia. This special issue emanated from a workshop sponsored by the World Health Organization in the Spring of 2002 on this topic. It is anticipated that these papers will help to establish guidelines for human exposure to conditions leading to hyperthermia. This comprehensive review of the literature makes it clear that much more work needs to be done to clarify what the thresholds for thermal damage are in humans. This review summarizes the basic principles that govern the relationships between thermal exposure (temperature and time of exposure) and thermal damage, with an emphasis on normal tissue effects. Methods for converting one time-temperature combination to a time at a standardized temperature are provided as well as a detailed discussion about the underlying assumptions that go into these calculations. There are few in vivo papers examining the type and extent of damage that occurs in the lower temperature range for hyperthermic exposures (e.g. 39-42 degrees C). Therefore, it is clear that estimation of thermal dose to effect at these thermal exposures is less precise in that temperature range. In addition, there are virtually no data that directly relate to the thermal sensitivity of human tissues. Thus, establishment of guidelines for human exposure based on the data provided must be done with significant caution. There is detailed review and presentation of thermal thresholds for tissue damage (based on what is detectable in vivo). The data are normalized using thermal dosimetric concepts. Tables are included in an Appendix Database which compile published data for thresholds of thermal damage in a variety of tissues and species. This database is available by request (contact MWD or PJH), but not included in this manuscript for brevity. All of the studies reported are for single acute thermal exposures. Except for brain function and physiology (as detailed in this issue by Sharma et al) one notes the critical lack of publications examining effects of chronic thermal exposures as might be encountered in occupational hazards. This review also does not include information on the embryo, which is covered in detail elsewhere in this volume (see article by Edwards et al.) as well as in a recent review on this subject, which focuses on thermal dose.

Quantitative and qualitative scintigraphic measurement of renal function in dogs exposed to toxic doses of Gentamicin.

Five, 3-month-old mongrel dogs weighing between 4.5 to 5.5 kg were studied to evaluate and compare the efficiency of 99mTc-DTPA, 99mTc-MAG3, and 99mTc-DMSA in detecting gentamicin-induced renal tubular injury. After baseline renograms using all three methods, all dogs received daily intramuscular injections of gentamicin at a dose of 30-45 mg/kg. Additional studies were obtained after a cumulative dose of 450, 1,575, and 2,250 mg of gentamicin was reached. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and percentage of total renal uptake measurements were calculated. Baseline and post-gentamicin injection blood urea nitrogen (BUN) and serum creatinine values were determined. A Duncan test revealed significant renal function impairment at 450 mgs of cumulated gentamicin with 99mTc-DMSA and at 1,575 mgs of cumulated gentamicin for 99mTc-DTPA and 99mTc-MAG3. There was no correlation between BUN and serum creatinine values when compared to gentamicin (p > 0.05). The images obtained with 99mTc-MAG3 were of better quality than those obtained with 99mTc-DTPA even under severe renal dysfunction. Percentage of 99mTc-DMSA uptake indicated renal damage, before than GFR and ERPF. BUN and serum creatinine measurements were poor indicators of gentamicin-induced renal failure.

Present state of development of neo-electroencephalography.

Neo-electroencephalography (neo-EEG) is a new technique for recording and analyzing brain activity. Mathematical and computerized reconstitution yields a monopolar-like montage. Given the polymorphism of the brain's electrical activity, the computer detects the correct monopolar-like montage for each activity in steps of 0.25 Hz. Conventional EEG detects the difference in potentials between two electrodes. Through the use of monopolar-like montages neo-EEG analysis reveals the amplitude and phase that actually underlie each electrode. The report describes with precision the features of the recording extracts that have been chosen for the analysis, i.e., the number of dominant frequencies, the frequency to the nearest 0.25 Hz and the frequency spectrum for each dominant frequency, then the amplitude to the nearest 0.1 microv and phase shift to the nearest 0.001 sec at each electrode. Some examples of comparisons between neo-EEG and conventional EEG findings are shown and demonstrate the advantages of neo-EEG in detection and differentiation of organic and functional pathologies.

Differential increased survival of staphylococci and limited ultrastructural changes in the core of infected fibrin clots after daptomycin administration.

A possible explanation for the difficulties encountered in curing deep fibrin-embedded infections is that antibiotic diffusion inside the infected fibrin matrix is not homogeneous and is insufficient to neutralize the pathogen. To evaluate this conjecture, the differential pharmacodynamics of daptomycin in fibrin clots infected with methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis was estimated. Daptomycin (20 or 50 mg/kg of body weight) was infused over 30 min. Fibrin clots and blood samples were evaluated from 0.5 to 42 h after the injections. The half-lives of daptomycin in serum and fibrin clot were close to identical after the two doses and averaged 5.4 and 22 h, respectively. The mean areas under the concentration-time curves from 0 to 42 h (AUC0-infinity) for daptomycin concentrations in serum and infected clots were 575 +/- 36.7 and 215 +/- 6.2 micrograms/g/h after administration of 20 mg/kg and 1,089 +/- 39.9 and 326 +/- 16.8 micrograms/g/h after administration of 50 mg/kg. A concentration gradient from the periphery to the core of the clots was observed in many clots up to 18 h after treatment. Mean peak concentrations in the core of the clots reached 60% of the peripheral values (P < 0.05) and were delayed for at least 3 h compared with the peripheral peak concentrations. AUC0-42 h of daptomycin concentration in the periphery and the core of clots were significantly different (P < 0.01). Survival of microorganisms was better in the core than in the periphery, with as much as a 3 log10 CFU/g difference between the center and the surface of the clot. Bacterial examination by transmission electron microscopy also showed noticeable differences in ultrastructural changes between those in the periphery and those in the core of the clots. In conclusion, the pharmacokinetics of daptomycin are significantly different at the periphery and within the core of fibrin clots, which may have led to the higher bacterial survival in the core of clots. Limited diffusion of daptomycin in fibrin, an essential component of the vegetation in bacterial endocarditis, could explain at least in part some of the treatment failures.

[Contribution of neo-electroencephalography in adult functional and psychiatric disorders]. / Apport de la néo-électro-encéphalographie dans les troubles fonctionnels et psychiatriques de l'adulte.

Two comparative studies of the basic activity at rest, with closed eyes taken in conventional EEG and analysed in Neo-EEG are carried out in adults showing functional or psychiatric disorders. The first open study involves 18 subjects suffering from a affection called "neurodystony" and 24 depressed subjects. The second study made in double-blind compares the results of the conventional EEG with the Neo-EEG in 19 depressed patients, 28 alcoholic patients and 26 psychotic patients. The Neo-EEG discloses abnormalities in about 60% of the cases when the conventional EEG is normal. The conventional EEG as well as the Neo-EEG diagnose a greater number of low voltage in alcoholic subjects and clear abnormalities in psychotic subjects. Low voltage is never detected in psychotic patients. In depressives, the Neo-EEG shows about 65% of abnormalities of which an asymmetry of the basic frequency in the center of the two hemispheres when they are analysed separately. That asymmetry develops in parallel with the clinical state. The asymmetry is also found in psychotic patients. In nervous or neurodystonic subjects, the Neo-EEG only discloses 25% of abnormalities. The Neo-EEG appears as an easy method, able to detect dysfunctions which cannot be disclosed with the conventional EEG and useful to follow their developments. Moreover, the result of this technique brings to the fore abnormalities not detected with the conventional EEG: this eventually leads to prescribe other therapies than those initially considered.

[MALT conjunctival lymphoma: how to treat?]. / Le caltome conjonctival: que faire?

A case of conjunctival lymphoma belonging to the MALT tissue is reported hereby. It is very uncommon in the literature, but special tools are needed to recognize this conjunctival involvement: Frozen sections of tissue to perform immunocytochemical studies. Investigations of the other lymphoid tissue, to assess the localized feature of the conjunctival disease.

Tissue distribution and excretion of radioactively labelled compounds in the Wistar rat after administration of [N-methyl-14C]-erythromycin A.

Tissue distribution and excretion of radioactively labelled compounds was studied in the Wistar rat after i.v. administration of [N-methyl-14C]-erythromycin A. Whole-body autoradiography and liquid scintillation counting was used to investigate the tissue localization of radioactivity in pregnant and non-pregnant rats. Tissue levels were maximal within 20 min, except for lachrymal glands, thymus and brain. Large amounts of radioactively labelled compounds, partly originating from active secretion, were present in the small intestine and caecum. Marked concentration of radioactively labelled compounds was also observed in the liver, spleen, lachrymal and salivary glands, lymph nodes, mammary glands, skin, bone marrow, and, to a lesser extent, in the lung, kidney and skeletal muscle. During six hours of experimental follow-up, plasma levels remained lower than corresponding tissue levels. At 1 h the radioactivity in fetuses was about three times lower than that in maternal blood. Within 48 h, more than 90% of the administered radioactivity was excreted. The amounts of radioactivity recovered in urine, faeces and expired air were about 19%, 48% and 24% respectively. After 48 h, 8% of the administered radioactivity was found in the carcass.