Annotated Whole-Genome Shotgun Sequence of Multidrug-Resistant Mycobacterium tuberculosis MTB13_M Isolated from Morocco.

Here, we describe the annotated genome sequence of Mycobacterium tuberculosis MTB13_M. The organism was isolated from a sputum sample in Morocco.

Peri-ictal water drinking and other ictal vegetative symptoms: Localizing and lateralizing the epileptogenic zone in temporal lobe epilepsy? Two case reports and review of the literature.

Peri-ictal behavior disorders can be helpful in localizing and lateralizing seizure onset in partial epilepsies, especially those originating in the temporal lobe. In this paper, we present the case of two right-handed women aged 36 and 42 years who presented with partial seizures of mesial temporal type. Both of the patients had drug resistant epilepsy and undergone presurgical evaluation tests including brain magnetic resonance imaging, video-EEG monitoring and neuropsychological testing. The two patients had hippocampal sclerosis in the right temporal lobe and exhibited PIWD behavior concomitant with right temporal lobe discharges documented during video-EEG recordings. Anterior temporal lobectomy was performed in one case with an excellent outcome after surgery. The patient was free of seizures at 3 years follow-up. We reviewed other publications of peri-ictal autonomic symptoms considered to have a lateralizing significance, such as peri-ictal vomiting, urinary urge, ictal pilo-erection. Clinicians should search for these symptoms, even if not spontaneously reported by the patient, because they are often under-estimated, both by the patients themselves and by physicians. Additionally, patients with lateralizing auras during seizures have a significantly better outcome after epilepsy surgery than those without lateralizing features.

Peptide YY, glucagon-like peptide-1, and neurotensin responses to luminal factors in the isolated vascularly perfused rat ileum.

Exposure of the ileum to nutrients markedly inhibits several upper gastrointestinal functions. Hormonal peptides of the ileal wall, i.e. peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and neurotensin (NT), are thought to play a role in this negative feedback mechanism. The present study was conducted to comparatively assess the secretion of PYY, GLP-1, and NT upon luminal infusion of a variety of individual luminal factors in the isolated vascularly perfused rat ileum preparation. PYY, GLP-1, and NT were measured in the portal effluent with specific RIAs. Glucose (250 mM) induced a pronounced release of the three peptides, whereas a physiological concentration of 5 mM did not induce peptide secretion. Peptone (5%, wt/vol) evoked a sustained release of PYY, GLP-1, and NT. Only NT secretion was increased upon luminal administration of 100 mM sodium oleate. Short chain fatty acids (20 mM) evoked an early and transient release of the three peptides. In contrast, taurocholate (20 mM) induced a sustained release of PYY, GLP-1, and NT, but the threshold concentration for peptide release was lower for NT than for PYY or GLP-1. Cellulose or pectin (0.5%, wt/vol) did not modify peptide secretion. In conclusion, glucose and peptone are potent stimulants of PYY, GLP-1, and NT release. Only NT is released upon oleic acid stimulation. Finally, taurocholate is a potent stimulant of the release of the three peptides. Overall, PYY, GLP-1, and NT may participate cooperatively in the ileal brake. As relatively high concentrations of the various stimulants were required to elicit peptide release, it seems likely that this mechanism operates in cases of maldigestion or malabsorption.

Regulation of glucagon-like peptide-1-(7-36) amide, peptide YY, and neurotensin secretion by neurotransmitters and gut hormones in the isolated vascularly perfused rat ileum.

Neurotensin (NT), peptide YY (PYY), and several peptides derived from proglucagon are promptly released from endocrine cells of the distal part of the gut after oral ingestion of a meal, thus suggesting that release of these peptides is partly under neural and/or hormonal control. Our previous studies conducted with a model of isolated vascularly perfused rat colon showed that colonic L cells are highly responsive to several transmitters of the gut and to the hormonal peptide GIP. To test the possibility that hormones produced by the proximal small intestine or transmitters of the enteric nervous system may also modulate the secretory activity of the ileal L cells, various intestinal regulatory peptides and neurotransmitters were administered intraarterially for 30 min in the isolated vascularly perfused rat ileum preparation. The secretory activity of the ileal N cells was comparatively assessed. The release of NT, PYY, and glucagon-like peptide-1 (GLP-1) in the portal effluent was measured with specific RIAs. The muscarinic cholinergic agonist bethanechol at a concentration of 10(-4) M provoked a biphasic release of PYY, GLP-1, and NT, consisting of an early peak followed by a sustained response. Similarly, bombesin (10(-7) M) induced a marked biphasic release of PYY and GLP-1. In contrast, the NT response was essentially monophasic, characterized by an early peak secretion. Tetrodotoxin did not modify the bombesin-induced release of PYY, GLP-1, and NT. The beta-adrenergic agonist isoproterenol at a concentration of 10(-6) M induced a transient rise in portal PYY and GLP-1 concentrations, whereas the effect on NT release was clearly biphasic. Calcitonin gene-related peptide (5 x 10(-8) M) induced a dramatic rise in PYY, GLP-1, and NT immunoreactivities in the portal effluent (peaks at 600%, 500%, and 550% of the basal values, respectively, 4 mi n after the start of infusion). Intraarterial infusion of GIP over the concentration range (0.5-3 nM) evoked a significant increase in portal concentration of the three peptides only at the threshold concentration of 3 nM. Secretin (50 pM) or cholecystokinin (50 pM) did not affect the release of ileal hormones. In conclusion, ileal L and N cells respond to a variety of transmitters of the gut. The pattern of peptide release depends on the cell type studied. The two cosynthesized peptides, PYY and GLP-1, appear to be cosecreted in the conditions of the present study.

Cholyltaurine absorption by the isolated vascularly perfused rat small bowel.

Isolated, vascularly perfused, rat duodenojejunum and ileum preparations were used to study the transport parameters of cholyltaurine (C-tau; taurocholate). After a bolus administration of C-tau containing trace amounts of [3H]C-tau into the lumen of the isolated vascularly perfused duodenojejunum, the rate of appearance of C-tau in the portal effluent was dose-dependent over the range 5-20 mM. At a concentration of 20 mM, the rate of absorption was constant over time and amounted to 1.25 nmol.min-1.cm-1; 2.6% of the luminal load of C-tau was recovered in the portal effluent over the 40-min experimental period. Intra-arterial infusion of ouabain (10(-3)M) did not modify significantly the absorption rate of C-tau. The C-tau absorption from the lumen of the isolated vascularly perfused ileum was 7-fold higher than that from the duodenojejunum. Total absorption of C-tau was dose-dependent over the range 1-20 mM and the estimated Km and Tmax of the absorptive area of the rat ileum were 11.5 mM and 17.7 nmol.min-1.cm-1, respectively. Intraarterial infusion of ouabain reduced by 84% the recovery of C-tau in the portal effluent. In conclusion, the absorption parameters of bile acids in the duodenojejunum and in the ileum of the ex vivo rat intestinal preparations are consistent with a passive diffusion process in the proximal small intestine and an active transport in the ileum. The isolated vascularly perfused duodenojejunum and ileum preparations are therefore appropriate models for studying bile acid absorption process and the coupling with the associated local metabolic, motor, secretory and vascular events.

Luminal bile salts and neurotensin release in the isolated vascularly perfused rat jejuno-ileum.

Bile salts in the distal small intestine are strong stimulants of neurotensin (NT) release, but the underlying mechanisms are not known. They were investigated using an isolated vascularly perfused rat jejuno-ileum preparation. Luminal administration of crude ox bile extract (0.25-1.5%, wt/vol) produced a dose-dependent release of NT-like immunoreactivity (NT-LI), with a maximal effect after infusion of 1% bile extract (500% of basal). Pretreatment of the 1% bile extract with the bile salt-sequestering resin cholestyramine (2%, wt/vol) abolished NT-LI release. Taurocholate (TC), the major bile salt in rats, dose dependently increased the release of NT. The maximal secretion of NT-LI was observed after infusion of 20 mM TC (400% of basal). Taurodeoxycholate (20 mM) was as potent as TC in stimulating NT-LI release, but the threshold concentration of taurodeoxycholate for NT-LI secretion was lower than that of TC. Glycocholate and cholate were 2- to 3-fold less potent than TC in releasing NT-LI over the concentration range 5-20 mM. Luminal infusion of oleic acid (sodium salt; 100 mM) increased by 100% the level of NT-LI in the portal effluent, whereas 20 mM oleate had no effect. In contrast, the micellar form of oleic acid (20 and 100 mM) in bile extract (1%) or TC (20 mM) dose dependently reduced the release of NT-LI induced by bile extract or TC alone. Neither intraarterial tetrodotoxin (10(-6) M), EGTA (2 mM), verapamil (5 x 10(-5) M), nor atropine (10(-5) M) had any effect on TC-induced NT-LI release. These results show that the tauro-conjugated forms of cholic and deoxycholic acid are strong stimulants of NT-LI release. The N-cell response is blunted when bile salts are complexed in the lumen by oleic acid. Finally, bile salt-induced NT-LI release is not mediated by intramural nerves and is not dependent on the activation of calcium channels.

Functional coupling between the active transport of glucose and the secretion of intestinal neurotensin in rats.

1. In this study, the mechanisms involved in the release of neurotensin-like immunoreactivity (NTLI) by glucose were investigated with the isolated, vascularly perfused rat jejunoileum preparation. 2. Luminal infusion of glucose (1-250 mM) produced a sharp and sustained release of NTLI in the intestinal venous effluent. The first significant response was observed with 5 mM glucose and the release reached a maximum under 250 mM glucose with a plateau secretion at 500% of basal. 3. There was no significant difference in the ability of galactose and 3-O-methylglucose to release NTLI when compared to glucose, but alpha-methylglucose, mannose, 2-deoxyglucose and fructose did not stimulate NTLI release. 4. Luminal infusion of 5 mM phloridzin reduced the glucose-induced release of NTLI by 90%. Intra-arterial infusion of glucose (25 mM) or of phloretin (20 microM) had no significant effect on the glucose-evoked NTLI secretion. 5. Intra-arterial infusion of ouabain (1 mM) produced a dramatic increase (at about 1500% of basal) in portal NTLI although it drastically reduced intestinal absorption of glucose. 6. Intra-arterial infusion of tetrodotoxin (1 microM), atropine (10 microM), verapamil (50 microM) or nifedipine (50 microM) did not modify the glucose-induced NTLI secretion. 7. Intra-arterial infusion of forskolin (2-20 microM) evoked a prompt and well-sustained secretion of NTLI which was increased to a mean value of 800% of basal with the highest dose tested. 3-Isobutyl-1-methylxanthine (IBMX, 10-100 microM) also stimulated the secretion of NTLI (maximal increase at 725% of basal at 100 microM). In contrast, intra-arterial infusion of 4-beta-phorbol 12-myristate, 13-acetate (PMA, 0.05-0.5 microM) had no effect on NTLI release. 8. IBMX (10-100 microM) synergistically enhanced NTLI responses induced by 250 mM glucose; the integrated response of NTLI release was 3- to 5-fold higher than the sum of individual responses produced by the same stimulants given separately. 9. It is concluded that the carbohydrate-induced NTLI release is related to the active, sodium-dependent hexose transport, but not to the carbohydrate catabolic pathway. Furthermore, the intramural nerves and L-type calcium channels are not involved in the glucose-induced NTLI secretion. Finally, the secretory activity of the intestinal N cell seems to be mainly stimulated through a cAMP-dependent pathway.

Bombesin potentiates taurocholic acid-induced neurotensin release in rats.

The hypothesis of synergistic effects between luminal stimulants and the intramural neural network in the control of intestinal neurotensin (NT) release was investigated with an isolated vascularly perfused rat jejuno-ileum. Luminal administration of low doses of taurocholic acid (TC; 1, 5, and 10 mM) provoked only a small increase in NT-like immunoreactivity (NT-LI) in the portal effluent (50%, 100%, and 130%, respectively, above basal). Increasing the concentration of TC to 20 mM induced a strong and sustained release of NT-LI (700% above basal). The arterial infusion of bombesin (BOM; 10(-9) M) induced only a transient rise in NT-LI levels (200% above basal), with a rapid return to basal values. In contrast, 10(-9) M BOM synergistically enhanced NT-LI responses induced by 10 mM TC; the integrated response of NT-LI release was 3.2-fold higher than the sum of responses to 10(-9) M BOM and 10 mM TC alone. These cooperative effects were apparent with 10(-10) M BOM and TC concentrations over the physiological range 1-10 mM. Neither tetrodotoxin (10(-6) M) nor atropine (10(-5) M) was able to modify this synergy. Substance-P and methacholine, two other NT secretagogues, did not potentiate the TC-induced NT responses. In conclusion, BOM potentiated the release of NT induced by TC, thus suggesting that bombesinergic neurons, among other stimulatory neurons of the enteric nervous system, may modulate the sensitivity of N-cells to luminal stimulants.

Release of ileal neurotensin in the rat by neurotransmitters and neuropeptides.

To investigate the functional relationship between the enteric nervous system and the intestinal neurotensin (N) cells, the release of neurotensin (NT) was measured upon vascular 8-min infusion periods of various neurotransmitters and neuropeptides in an isolated vascularly perfused rat jejunoileum. NT-like immunoreactivity (NT-LI) was measured with an antiserum that specifically recognizes intact NT. The cholinergic agonists methacholine and carbachol produced a strong release of NT-LI (250% and 700% of basal, respectively at 10(-5) M). The infusion of a lower dose (10(-7) M) was less effective in both cases. The nicotinic receptor agonist DMPP (10(-4) M) had no significant effect on NT-LI release. Norepinephrine (10(-6) M) produced a moderate and well-sustained secretion of NT (200% of basal). Infusion of higher doses of these neurotransmitters dramatically increased the arterial pressure. G-amino-n-butyric acid (GABA), histamine, serotonin and dopamine administered at final concentrations up to 10(-5) M had no effect on NT-LI release. In contrast, gastrin-releasing peptide and bombesin induced a dose-dependent transient increase of portal NT-LI (maximal value at 10(-7) M: 1000% of basal) followed by a rapid return to near basal values. Substance P (10(-7) M) evoked a prompt release of NT-LI with a peak at 600% of basal followed by a decline to 200% of basal at the end of the session. Leu-enkephalin and calcitonin-gene-related-peptide (CGRP, 10(-7) M) produced a small rise in portal NT-LI, while Met-enkephalin, dynorphin, vasoactive intestinal peptide (VIP), galanin, neuropeptide Y (NPY), peptide histidine isoleucine (PHI), neuromedin U and thyrotropin releasing hormone (TRH) had no stimulatory effect. Our results indicate that additionally to the secretion of NT induced by cholinergic agents and bombesin, substance P and to a lesser extent Leu-enkephalin are capable of stimulating NT release in the rat.