Conditional risk of diverticulitis after non-operative management.

BACKGROUND: The objective of this study was to describe conditional recurrence-free survival (RFS) of patients after an index episode of diverticulitis managed without surgery, and to estimate the difference in conditional RFS for diverticulitis according to specific risk factors. METHODS: This was a multicentre retrospective cohort study including all patients managed without surgery for acute sigmoid diverticulitis at two university-affiliated hospitals in Montreal, Quebec, Canada. Conditional RFS for diverticulitis was estimated over 10 years of follow-up. A Cox proportional hazards model was performed at the index episode and again 2 years later. RESULTS: In total, 991 patients were included for analysis. The 1, 2- and 3-year actuarial diverticulitis RFS rates were 81·1, 71·5 and 67·5 per cent respectively. Compared with the 1-year actuarial RFS rate of 81·1 per cent, the 1-year conditional RFS increased with each additional year survived recurrence-free, reaching 96·0 per cent after surviving the first 4 years recurrence-free. A similar phenomenon was observed for 2-year diverticulitis conditional RFS. Lower age (hazard ratio (HR) 0·98, 95 per cent c.i. 0·98 to 0·99), Charlson Co-morbidity Index score of 2 or above (HR 1·78, 1·32 to 2·39) and immunosuppression (HR 1·85, 1·38 to 2·48) were independently associated with recurrence of diverticulitis from the index episode. At 2 years from the index episode, immunosuppression was no longer associated with diverticulitis recurrence (HR 1·02, 0·50 to 2·09). CONCLUSION: The conditional RFS of patients with diverticulitis improved with each year that was survived recurrence-free. Although several factors at index presentation may be associated with early recurrence, the conditional probability of recurrence according to many of these risk factors converged with time.

ANTECEDENTES: El objetivo de este estudio fue describir la supervivencia condicional libre de recidiva de diverticulitis (diverticulitis recurrence-free survival, Div-RFS) en pacientes tras un episodio de diverticulitis tratado de forma conservadora, y calcular la diferencia en la Div-RFS condicional de acuerdo con factores de riesgo específicos. MÉTODOS: Estudio de cohorte retrospectivo multicéntrico que incluyó a todos los pacientes tratados de forma no quirúrgica por diverticulitis sigmoidea aguda en dos hospitales afiliados a la universidad en Montreal, Quebec, Canadá. La supervivencia condicional libre de recidiva de la diverticulitis se calculó durante 10 años de seguimiento. Se realizó un análisis mediante un modelo de riesgos proporcionales de Cox en el episodio índice y nuevamente 2 años después. RESULTADOS: En total, se incluyeron 991 pacientes en el análisis. La Div-RFS actuarial a 1, 2 y 3 años fue del 81,1%, 71,5% y 67,5%, respectivamente. En comparación con la Div-RFS actuarial a 1 año del 81,1%, la Div-RFS condicional a 1 año aumentó con cada año adicional sobrevivido sin recidiva, alcanzando el 96,0% después de sobrevivir los primeros 4 años sin recidiva. Se observó un fenómeno similar para Div-RFS condicional a los 2 años. Una menor edad (cociente de riesgos instantáneos, hazard ratio, HR: 0,98; i.c. del 95%: 0,98 a 0,99), la puntuación de comorbilidad de Charlson ≥ 2 (HR: 1,78; i.c. del 95%: 1,32 a 2,39) y la inmunosupresión (HR: 1,85; i.c. del 95%: 1,38 a 2,48) se asociaron de forma independiente con la recidiva de la diverticulitis desde el episodio índice. En la regresión de Cox a los 2 años del episodio índice, la inmunosupresión ya no se asoció con recidiva de diverticulitis (HR: 1,02; i.c. del 95% 0,50-2,09). CONCLUSIÓN: La Div-RFS condicional mejoró con cada año de supervivencia sin recidiva. Si bien varios factores en la presentación del episodio índice pueden estar asociados con una recidiva precoz, la probabilidad condicional de recidiva en relación con muchos de estos factores de riesgo coincidió con el tiempo.

Assessing the readability, quality and accuracy of online health information for patients with low anterior resection syndrome following surgery for rectal cancer.

AIM: Management of low anterior resection syndrome (LARS) requires a high degree of patient engagement. This process may be facilitated by online health-related information and education. The aim of this study was to systematically review current online health information on LARS. METHOD: An online search of Google, Yahoo and Bing was performed using the search terms 'low anterior/anterior resection syndrome' and 'bowel function/movements after rectal cancer surgery'. Websites were assessed for readability (eight standardized tests), suitability (using the Suitability Assessment of Materials instrument), quality (the DISCERN instrument), accuracy and content (using a LARS-specific content checklist). Websites were categorized as academic, governmental, nonprofit or private. RESULTS: Of 117 unique websites, 25 met the inclusion criteria. The median readability level was 10.4 (9.2-11.7) and 11 (44.0%) websites were highly suitable. Using the DISCERN instrument, seven (28.0%) websites had clear aims, two (8.0%) divulged the sources used and four (16.0%) had high overall quality. Only eight (32.0%) websites defined LARS and ten (40.0%) listed all five major symptoms associated with the LARS score. There was variation in the number of websites that discussed dietary modifications (80.0%), self-help strategies (72.0%), medication (68.0%), pelvic floor rehabilitation (60.0%) and neuromodulation (8.0%). The median accuracy of websites was 93.8% (88.2-96.7%). Governmental websites scored highest for overall suitability (P = 0.0079) and quality (P < 0.001). CONCLUSIONS: Current online information on LARS is suboptimal. Websites are highly variable, important content is often lacking and material is too complex for patients.

Study protocol evaluating the use of bowel stimulation before loop ileostomy closure to reduce postoperative ileus: a multicenter randomized controlled trial.

AIM: Postoperative ileus is the most commonly observed morbidity following ileostomy closure. Studies have demonstrated that the defunctionalized bowel of a loop ileostomy undergoes a series of functional and structural changes, such as atrophy of the intestinal villi and muscular layers, which may contribute to ileus. A single-centre study in Spain demonstrated that preoperative bowel stimulation via the distal limb of the loop ileostomy decreased postoperative ileus, length of stay and time to gastrointestinal function. METHOD: A multicentre randomized controlled trial involving patients from Canadian institutions was designed to evaluate the effect of preoperative bowel stimulation before ileostomy closure on postoperative ileus. Stimulation will include canalizing the distal limb of the ileostomy loop with an 18Fr Foley catheter and infusing it with a solution of 500 ml of normal saline mixed with 30 g of a thickening agent (Nestle© Thicken-Up© ). This will be performed 10 times over the 3 weeks before ileostomy closure in an outpatient clinic setting by a trained Enterostomal Therapy nurse. Surgeons and the treating surgical team will be blinded to their patient's group allocation. Data regarding patient demographics, and operative and postoperative variables, will be collected prospectively. Primary outcome will be postoperative ileus, defined as an intolerance to oral food in the absence of clinical or radiological signs of obstruction, that either requires nasogastric tube insertion or is associated with two of the following on or after post-operative day 3: nausea/vomiting; abdominal distension; and the absence of flatus. Secondary outcomes will include length of stay, time to tolerating a regular diet, time to first passage of flatus or stool and overall morbidity. A cost analysis will be performed to compare the costs of conventional care with conventional care plus preoperative stimulation. DISCUSSION: This manuscript discusses the potential benefits of preoperative bowel stimulation in improving postoperative outcomes and outlines our protocol for the first multicenter study to evaluate preoperative bowel stimulation before ileostomy closure. The results of this study could have considerable implications for the care of patients undergoing ileostomy closure.

[Development and validation of an analytical method to quantify residues of cleaning products able to inactivate prion]. / Développement et validation d'une méthode de dosage des traces de détergents inactivants totaux du prion.

OBJECTIVES: In this study, a novel analytical method to quantify prion inactivating detergent in rinsing waters coming from the washer-disinfector of a hospital sterilization unit has been developed. The final aim was to obtain an easy and functional method in a routine hospital process which does not need the cleaning product manufacturer services. METHODS: An ICP-MS method based on the potassium dosage of the washer-disinfector's rinsing waters was developed. Potassium hydroxide is present on the composition of the three prion inactivating detergent currently on the French market. The detergent used in this study was the Actanios LDI(®) (Anios laboratories). A Passing and Bablok regression compares concentrations measured with this developed method and with the HPLC-UV manufacturer method. RESULTS: According to results obtained, the developed method is easy to use in a routine hospital process. The Passing and Bablok regression showed that there is no statistical difference between the two analytical methods during the second rinsing step. Besides, both methods were linear on the third rinsing step, with a 1.5ppm difference between the concentrations measured for each method. CONCLUSIONS: This study shows that the ICP-MS method developed is nonspecific for the detergent, but specific for the potassium element which is present in all prion inactivating detergent currently on the French market. This method should be functional for all the prion inactivating detergent containing potassium, if the sensibility of the method is sufficient when the potassium concentration is very low in the prion inactivating detergent formulation.

The presence and leachability of antimony in different wastes and waste handling facilities in Norway.

The environmental behaviour of antimony (Sb) is gathering attention due to its increasingly extensive use in various products, particularly in plastics. Because of this it may be expected that plastic waste is an emission source for Sb in the environment. This study presents a comprehensive field investigation of Sb concentrations in diverse types of waste from waste handling facilities in Norway. The wastes included waste electrical and electronic equipment (WEEE), glass, vehicle fluff, combustibles, bottom ash, fly ash and digested sludge. The highest solid Sb concentrations were found in WEEE and vehicle plastic (from 1238 to 1715 mg kg(-1)) and vehicle fluff (from 34 to 4565 mg kg(-1)). The type of acid used to digest the diverse solid waste materials was also tested. It was found that HNO3:HCl extraction gave substantially lower, non-quantitative yields compared to HNO3:HF. The highest water-leachable concentration for wastes when mixed with water at a 1 : 10 ratio were observed for plastic (from 0.6 to 2.0 mg kg(-1)) and bottom ash (from 0.4 to 0.8 mg kg(-1)). For all of the considered waste fractions, Sb(v) was the dominant species in the leachates, even though Sb(iii) as Sb2O3 is mainly used in plastics and other products, indicating rapid oxidation in water. This study also presents for the first time a comparison of Sb concentrations in leachate at waste handling facilities using both active grab samples and DGT passive samples. Grab samples target the total suspended Sb, whereas DGT targets the sum of free- and other chemically labile species. The grab sample concentrations (from 0.5 to 50 µg L(-1)) were lower than the predicted no-effect concentration (PNEC) of 113 µg L(-1). The DGT concentrations were substantially lower (from 0.05 to 9.93 µg L(-1)) than the grab samples, indicating much of the Sb is present in a non-available colloidal form. In addition, air samples were taken from the chimney and areas within combustible waste incinerators, as well as from the vent of WEEE sorting facility. The WEEE vent had the highest Sb concentration (from <100 to 2200 ng m(-3)), which were orders of magnitude higher than the air surrounding the combustible shredder (from 25 to 217 ng m(-3)), and the incinerator chimney (from <30 to 100 ng m(-3)). From these results, it seems evident that Sb from waste is not an environmental concern in Norway, and that Sb is mostly readily recovered from plastic and bottom ash.

Lasting alterations of the sodium current by short-term hyperlipidemia as a mechanism for initiation of cardiac remodeling.

Clinical and animal studies indicate that increased fatty acid delivery to lean tissues induces cardiac electrical remodeling and alterations of cellular calcium homeostasis. Since this may represent a mechanism initiating cardiac dysfunction during establishment of insulin resistance and diabetes or anaerobic cardiac metabolism (ischemia), we sought to determine if short-term exposure to high plasma concentration of fatty acid in vivo was sufficient to alter the cardiac sodium current (INa) in dog ventricular myocytes. Our results show that delivery of triglycerides and nonesterified fatty acids by infusion of Intralipid + heparin (IH) for 8 h increased the amplitude of INa by 43% and shifted its activation threshold by -5 mV, closer to the resting membrane potential. Steady-state inactivation (availability) of the channels was reduced by IH with no changes in recovery from inactivation. As a consequence, INa "window" current, a strong determinant of intracellular Na+ and Ca2+ concentrations, was significantly increased. The results indicate that increased circulating fatty acids alter INa gating in manners consistent with an increased cardiac excitability and augmentation of intracellular calcium. Moreover, these changes could still be measured after the dogs were left to recover for 12 h after IH perfusion, suggesting lasting changes in INa. Our results indicate that fatty acids rapidly induce cardiac remodeling and suggest that this process may be involved in the development of cardiac dysfunctions associated to insulin resistance and diabetes.

P21-activated kinase 4 (PAK4) is required for metaphase spindle positioning and anchoring.

The oncogenic kinase PAK4 was recently found to be involved in the regulation of the G1 phase and the G2/M transition of the cell cycle. We have also identified that PAK4 regulates Ran GTPase activity during mitosis. Here, we show that after entering mitosis, PAK4-depleted cells maintain a prolonged metaphase-like state. In these cells, chromosome congression to the metaphase plate occurs with normal kinetics but is followed by an extended period during which membrane blebbing and spindle rotation are observed. These bipolar PAK4-depleted metaphase-like spindles have a defective astral microtubule (MT) network and are not centered in the cell but are in close contact with the cell cortex. As the metaphase-like state persists, centrosome fragmentation occurs, chromosomes scatter from the metaphase plate and move toward the spindle poles with an active spindle assembly checkpoint, a phenotype that is reminiscent of cohesion fatigue. PAK4 also regulates the acto-myosin cytoskeleton and we report that PAK4 depletion results in the induction of cortical membrane blebbing during prometaphase arrest. However, we show that membrane blebs, which are strongly enriched in phospho-cofilin, are not responsible for the poor anchoring of the spindle. As PAK4 depletion interferes with the localization of components of the dynein/dynactin complexes at the kinetochores and on the astral MTs, we propose that loss of PAK4 could induce a change in the activities of motor proteins.

Determination of the uptake and release rates of multifamilies of endocrine disruptor compounds on the polar C18 Chemcatcher. Three potential performance reference compounds to monitor polar pollutants in surface water by integrative sampling.

The uptake kinetics of 27 emerging pollutants on the polar C18 Chemcatcher have been investigated. This investigation determined the sampling rates of 20 compounds, including 16 endocrine disruptors and 4 pharmaceuticals, which were used as overall pollution indicators. Calibrations were completed in a 50-L flow-through microcosm with continuous renewal of tap water spiked with approximately 3 µg/L of each pollutant and with sampling times at 1, 3, 6 and 12h and 1, 3, 7, 14, 21 and 28 days. Exponential regressions for the accumulation kinetics were plotted to confirm the maximum linear uptake times for each molecule using the half time of equilibrium (t(1/2)) criteria. Of the compounds tested, 17 were accumulated linearly for up to 14 or 21 days with an R(2) above 0.98 for linear correlations. The evaluation of the release kinetics of a C18 Chemcatcher spiked with 20 deuterated compounds identified 3 potential performance reference compounds (PRCs) with exponential desorption rates showing relatively good isotropic exchange.

Genome sequence of the edible cyanobacterium Arthrospira sp. PCC 8005.

We determined the genome sequence of Arthrospira sp. PCC 8005, a cyanobacterial strain of great interest to the European Space Agency for its nutritive value and oxygenic properties in the Micro-Ecological Life Support System Alternative (MELiSSA) biological life support system for long-term manned missions into space.

Analysis of bovine sexed sperm for IVF from sorting to the embryo.

The objective of this study was to characterize bovine semen parameters and determine the best IVF conditions to produce a maximal percentage of blastocysts. Four types of semen were analyzed with CASA and flow cytometry: fresh and frozen non-sexed semen; fresh and frozen sexed semen. Semen was obtained from four Holstein bulls and two ejaculates from each bull were analyzed. Oocytes from slaughterhouse ovaries were matured and fertilized in vitro with all types of semen (for sexed semen, 2, 5 or 10microg/mL heparin was added to the IVF media while for non-sexed semen, 10microg/mL was added in the IVF medium). Presumptive zygotes were co-cultured with Buffalo rat liver cells in Menezo's B2 medium, and cleavage rates at Day 2, and blastocyst rates at Day 7 of culture, were recorded. Sexed semen resulted in fewer blastocysts than non-sexed semen (P<0.05), and certain bulls performed better in IVF. Freezing, and not sexing, had a more significant negative effect on semen quality. Compromised semen quality due to sexing and/or freezing can explain the reduced in vitro blastocyst rates when using frozen-thawed sexed semen. Sexed semen that appeared more capacitated seemed to require less heparin in IVF than sexed semen that appeared less capacitated to produce a maximal percentage of blastocyst. Flow cytometry sorting eliminates spermatozoa that possess compromised DNA, and therefore the reduced fertility seen in vitro is not due to an increased percentage of spermatozoa with compromised DNA. This study describes tools that can monitor semen parameters to optimize IVF conditions and thus obtain maximal blastocyst rates.

Activated polymorphonuclear cells promote injury and excitability of dorsal root ganglia neurons.

Therapies aimed at depleting or blocking the migration of polymorphonuclear leukocytes (PMN or neutrophils) are partially successful in the treatment of neuroinflammatory conditions and in attenuating pain following peripheral nerve injury or subcutaneous inflammation. However, the functional effects of PMN on peripheral sensory neurons such as dorsal root ganglia (DRG) neurons are largely unknown. We hypothesized that PMN are detrimental to neuronal viability in culture and increase neuronal activity and excitability. We demonstrate that isolated peripheral PMN are initially in a relatively resting state but undergo internal oxidative burst and activation by an unknown mechanism within 10 min of co-culture with dissociated DRG cells. Co-culture for 24 h decreases neuronal count at a threshold<0.4:1 PMN:DRG cell ratio and increases the number of injured and apoptotic neurons. Within 3 min of PMN addition, fluorometric calcium imaging reveals intracellular calcium transients in small size (<25 microm diam) and large size (>25 microm diam) neurons, as well as in capsaicin-sensitive neurons. Furthermore, small size isolectin B4-labeled neurons undergo hyperexcitability manifested as decreased current threshold and increased firing frequency. Although co-culture of PMN and DRG cells does not perfectly model neuroinflammatory conditions in vivo, these findings suggest that activated PMN can potentially aggravate neuronal injury and cause functional changes to peripheral sensory neurons. Distinguishing the beneficial from the detrimental effects of PMN on neurons may aid in the development of more effective drug therapies for neurological disorders involving neuroinflammation, including painful neuropathies.

Contribution of estrogen receptors alpha and beta to the effects of estradiol in the brain.

Clinical and experimental studies show a modulatory role of estrogens in the brain and suggest their beneficial action in mental and neurodegenerative diseases. The estrogen receptors ERalpha and ERbeta are present in the brain and their targeting could bring selectivity and reduced risk of cancer. Implication of ERs in the effect of estradiol on dopamine, opiate and glutamate neurotransmission is reviewed. The ERalpha agonist, PPT, is shown as estradiol to modulate hippocampal NMDA receptors and AMPA receptors in cortex and striatum of ovariectomized rats whereas the ERbeta agonist DPN is inactive. Striatal DPN activity suggests implication of ERbeta in estradiol modulation of D2 receptors and transporters in ovariectomized rats and is supported by the lack of effect of estradiol in ERbeta knockout (ERKObeta) mice. Both ERalpha and ERbeta agonists modulate striatal preproenkephalin (PPE) gene expression in ovariectomized rats. In male mice PPT protects against MPTP toxicity to striatal dopamine; this implicates Akt/GSK3beta signaling and the apoptotic regulators Bcl2 and Bad. This suggests a role for ERalpha in striatal dopamine neuroprotection. ERKOalpha mice are more susceptible to MPTP toxicity and not protected by estradiol; differences in ERKObeta mice are subtler. These results suggest therapeutic potential for the brain of ER specific agonists.

Neutrophils invade lumbar dorsal root ganglia after chronic constriction injury of the sciatic nerve.

To test whether neutrophils (PMN) target lumbar dorsal root ganglia (DRG) following axonal injury leading to neuropathic pain, we visualized PMN infiltration in DRG tissue sections and estimated PMN count by flow cytometry following sciatic chronic constriction injury (CCI). Seven days after CCI, results show PMN within DRG where their count increased by three fold ipsilateral to injury compared to contralateral or sham, concomitant with peak neuropathic pain behavior. Superoxide burst in PMN isolated from rats d7 after CCI was elevated by 170% +/-18 compared to naïve and MCP-1 mRNA expression in DRG increased by 8.9+/-2.9 fold, but that of MIP-2, CINC-1, and RANTES did not change. We conclude that CCI causes PMN invasion of the DRG whereby the functional implication of their close proximity to neuronal axon and soma remains unknown.

Oestrogens prevent loss of dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) in substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice.

Previous results from our laboratory have shown that 17beta-oestradiol prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) striatal dopamine depletion. 17beta-oestradiol, oestriol and oestrone are the naturally occurring oestogens in humans. Using various dopamine markers, the present study investigated whether oestrone and oestriol such as 17beta-oestradiol have neuroprotective activity in MPTP-treated mice. Male mice were treated with 17beta-oestradiol, oestriol or oestrone for 5 days before and after MPTP administration, and were compared with nonlesioned mice receiving the same treatment. Striatal concentrations of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were assayed by high-performance liquid chromatography. Dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) specific binding were measured by autoradiography. DAT, VMAT2 and tyrosine hydroxylase mRNA levels were measured by in situ hybridisation. MPTP induced a loss of DAT and VMAT2 specific binding in the striatum and substantia nigra, as well as a decrease of VMAT2 mRNA in the substantia nigra. 17beta-oestradiol treatment prevented the loss of these dopaminergic markers, as well as striatal concentrations of dopamine, DOPAC and HVA. Mice receiving oestriol and oestrone showed catecholamine concentrations comparable to MPTP mice. Oestriol treatment had no effect on dopaminergic markers in MPTP mice whereas oestrone prevented striatal DAT loss and the decrease of VMAT2 mRNA in the substantia nigra. In nonlesioned mice, 17beta-oestradiol, oestriol or oestrone had no effect on all the dopaminergic markers investigated. In conclusion, a weak or a lack of effect of oestriol and oestrone was observed compared to 17beta-oestradiol in MPTP mice and none of these steroids had an effect in nonlesioned mice. A DAT and VMAT2 specific binding decrease after MPTP in the striatum and substantia nigra, as well as a decrease of substantia nigra VMAT2 mRNA, was observed and could be prevented by oestradiol.

Right spatial neglect after left hemisphere stroke: qualitative and quantitative study.

OBJECTIVES: Comparatively little research has been conducted on right neglect after left brain damage. The authors sought to assess contralateral neglect in subacute left hemisphere stroke patients using a comprehensive test battery validated in a large control group after right hemisphere stroke. METHODS: Seventy-eight left hemisphere stroke patients were assessed. The test battery included a preliminary assessment of anosognosia and visual extinction, a clinical assessment of gaze orientation and personal neglect, and paper-and-pencil tests of spatial neglect in the peripersonal space. Only nonverbal tests were used. RESULTS: Drawing and cancellation tasks revealed neglect in 10 to 13% of patients. The combined battery was more sensitive than any single test alone. A total of 43.5% of patients showed some degree of neglect on at least one measure. Anatomic analyses showed that neglect was more common and severe when the posterior association cortex was damaged. CONCLUSIONS: The frequency of occurrence of right neglect was, as expected, much lower than that reported in a study using the same assessment battery in right brain damage stroke patients. Nevertheless, neglect was found in a substantial proportion of patients at a subacute stage, suggesting that it should be considered in the rehabilitation planning of left brain damage stroke patients.

[Two cases of non-functional gonadotroph adenoma pituitary apoplexy following GnRH-agonist treatment revealing gonadotroph adenoma and pseudopituitary apoplexy after GnRH administration]. / Deux cas de macroadénomes gonadotropes silencieux: apoplexie hypophysaire au décours d'une première injection d'agoniste de la LH-RH révélant un adénome gonadotrope. Pseudoapoplexie hypophysaire d'un adénome gonadotrope au décours d'un test de stimulation.

We report here two cases of pituitary apoplexy or pseudoapoplexy revealing a gonadotroph adenoma. A 69-year-old man, who had just started antiandrogen treatment (Gn-RH agonist) for prostatic cancer, was admitted to neurosurgery emergency because of increasing headache and visual impairment. The CT-scan disclosed the presence of a large pituitary mass with lateral invasion of the left cavernous sinus. Hormonel testing showed panhypopituitarism. A few days later, diabetes insipidus appeared. The patient first received corticosteroid therapy and underwent surgical adenomectomy. Immunostaining of the tumor tissue was positive for FSHbeta, confirming the diagnosis of gonadotroph adenoma. Three months after surgery, the endocrine evaluation showed pituitary insufficiency. An 81-year-old man complained of mnemonic disorders. The CT-scan revealed a pituitary mass without extension. The Ophthalmological examination showed left temporal upper quadranopsia. Endocrinological tests with administration of GN-HR triggered headache and vomiting. A second CT-scan was unchanged. Hormone testing revealed increased serum levels of FSH and decreased serum levels of LH. Surgical management of the primary tumor was undertaken due to the visual field alteration. Immunohistochemical studies confirmed the diagnosis of gonadotroph FSHbeta adenoma.

Effect of prolonged treatment with tyramine on glucose tolerance in streptozotocin-induced diabetic rats.

The biogenic amine tyramine has been reported to stimulate in vitro glucose transport in adipocytes, cardiomyocytes and skeletal muscle, and to improve in vivo glucose utilization in rats. These effects were dependent on amine oxidation, since they were blocked by inhibitors of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO). We thus tested in this work whether a prolonged treatment with tyramine could improve glucose tolerance in streptozotocin-induced diabetic rats. First, tyramine content of standard rodent chow was determined by HPLC and daily tyramine intake of control rats was estimated to be around 26 micromol/kg body weight. Then, tyramine was administred during 3 weeks in streptozotocin-induced diabetic rats at 29 micromol/kg by daily i.p. injection alone or together with vanadate 0.02 micromol/kg. In another group of diabetic rats, tyramine was subcutaneously delivered at 116 micromol/kg/day by osmotic minipumps. All tyramine treatments resulted in a decrease of the hyperglycemic responses to an i.p. glucose load. Adipocytes isolated from either untreated or treated diabetic rats were sensitive to the stimulation of glucose uptake by tyramine. However, diabetic animals receiving tyramine for three weeks did not recover from their hyperglycemia, hypoinsulinemia and glucosuria. These results show that the improvement of glucose tolerance induced by prolonged tyramine administration occurs in an insulin-depleted model and probably results from peripheral insulin-like actions of the oxidation of MAO/SSAO substrates, such as the stimulation of glucose uptake into adipocytes.

Characterization of semicarbazide-sensitive amine oxidase in human subcutaneous adipocytes and search for novel functions.

Numerous studies have characterized semicarbazide-sensitive amine oxidase activity (SSAO) in rat fat cells but this oxidase is scarcely documented in human adipose tissue. Our aim was to further characterize SSAO in human adipose tissue (activity, mRNA and protein abundance) and to investigate whether SSAO activity can interplay with glucose and lipid metabolism in human adipocytes via the hydrogen peroxide it generates. Polyclonal antibodies directed against bovine lung SSAO allowed the detection of a substantial amount of immunoreactive protein (apparent molecular mass 100 kDa) in human subcutaneous adipocytes from either mammary or abdominal fat depots. A 4-kb mRNA was detected in fat depots using a cDNA probe designed from the placenta SSAO sequence. Almost all the oxidation of benzylamine found in adipose tissue homogenates was due to fat cells and was located in the adipocyte membrane fraction. The oxidation of benzylamine and methylamine were similar and totally inhibited by semicarbazide or hydralazine but resistant to pargyline. Histamine was poorly oxidized. Benzylamine and methylamine dose-dependently stimulated glucose transport in intact adipocytes. This insulin-like effect of amines did not increase in the presence of 0.1 mM vanadate but was inhibited by semicarbazide and antioxidants. Benzylamine and methylamine also exhibited antilipolytic effects, with complete inhibition of lipolysis at 1 mM. These results show that fat cells from non-obese subjects express a membrane-bound SSAO which readily oxidizes exogenous amines, generates hydrogen peroxide and exerts short-term insulin-like actions on glucose and lipid metabolism.