Lymphadenectomy in gastric cancer: our experience with 180 cases.
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Adenocarcinoma↗
Biomedical subjects
L Negri
Publications and source records attributed to L Negri.
Divided vertical banded gastroplasty either for correction or as a first-choice operation.
BACKGROUND: Staple-line disruption may occur after vertical banded gastroplasty (VBG). METHODS: Since May 1996, the authors have performed the gastric restrictive procedure divided VBG, as described by MacLean, as a first-choice operation and not only as correction for staple-line breakdown. Divided VBG was done in 111 patients, 32 as correction after staple-line disruption and 79 as a first choice, 29 of them by hand-assisted laparoscopy with the dexterity pneumosleeve. RESULTS: Weight loss and nutritional status have been very satisfactory. Operating time for the standardized operation has been no longer than 60 minutes. CONCLUSION: Divided VBG, especially if done by hand-assisted laparoscopy using the dexterity pneumosleeve, is a valid restrictive procedure.
Adult↗
Genic amplification test in the diagnosis of mammary and disseminated tuberculosis.
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Aged↗
Activity of the delta-opioid receptor is partially reduced, whereas activity of the kappa-receptor is maintained in mice lacking the mu-receptor.
Previous pharmacological studies have indicated the possible existence of functional interactions between mu-, delta- and kappa-opioid receptors in the CNS. We have investigated this issue using a genetic approach. Here we describe in vitro and in vivo functional activity of delta- and kappa-opioid receptors in mice lacking the mu-opioid receptor (MOR). Measurements of agonist-induced [35S]GTPgammaS binding and adenylyl cyclase inhibition showed that functional coupling of delta- and kappa-receptors to G-proteins is preserved in the brain of mutant mice. In the mouse vas deferens bioassay, deltorphin II and cyclic[D-penicillamine2, D-penicillamine5] enkephalin exhibited similar potency to inhibit smooth muscle contraction in both wild-type and MOR -/- mice. delta-Analgesia induced by deltorphin II was slightly diminished in mutant mice, when the tail flick test was used. Deltorphin II strongly reduced the respiratory frequency in wild-type mice but not in MOR -/- mice. Analgesic and respiratory responses produced by the selective kappa-agonist U-50,488H were unchanged in MOR-deficient mice. In conclusion, the preservation of delta- and kappa-receptor signaling properties in mice lacking mu-receptors provides no evidence for opioid receptor cross-talk at the cellular level. Intact antinociceptive and respiratory responses to the kappa-agonist further suggest that the kappa-receptor mainly acts independently from the mu-receptor in vivo. Reduced delta-analgesia and the absence of delta-respiratory depression in MOR-deficient mice together indicate that functional interactions may take place between mu-receptors and central delta-receptors in specific neuronal pathways.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
A new opioid peptide predicted from cloned cDNAs from skin of Pachymedusa dacnicolor and Agalychnis annae.
We have isolated a cDNA encoding a precursor of dermorphin from the skin of Pachymedusa dacnicolor. Besides four copies of this opioid peptide, the deduced sequence also contains the genetic information for a novel peptide Tyr-Ile-Phe-His-Leu-Met-Asp-NH2. This differs from Met-deltorphin by the presence of Ile at position 2. In a related precursor from the skin of Agalychnis annae, the sequence of this peptide is in the 3'-untranslated region of the cloned cDNA. From earlier results we predict that in skin peptides the second residue is D-allo-Ile. We have synthesized this and related peptides with different D-amino acids, and determined their delta agonist activity. The peptide with D-nor-Leu binds with high affinity to delta receptors, while that with D-allo-Ile is about 100 times less active.
Amino Acid Sequence↗
Respiratory and cardiovascular effects of the mu-opioid receptor agonist [Lys7]dermorphin in awake rats.
1. Changes in respiratory variables, arterial blood pressure and heart rate were studied in awake rats after injection of the opioid peptide [Lys7]dermorphin and its main metabolites, [1-5]dermorphin and [1-4]dermorphin. 2. Fifteen minutes after injection, doses of [Lys7]dermorphin producing antinociception (i.c.v., 36-120 nmol; s.c., 0.12-4.7 micromol kg(-1)) significantly increased respiratory frequency and minute volume of rats breathing air or hypoxic inspirates. This respiratory stimulation was reversed to depression by the 5-HT receptor antagonist ritanserin (2 mg kg(-1), s.c.), was blocked by naloxone (0.1 mg kg(-1), s.c.), significantly reduced by the mu1 opioid receptor antagonist naloxonazine (10 mg kg(-1), s.c., 24 h before) but unaffected by peripherally acting opioid antagonist naloxone methyl bromide (3 mg kg(-1), s.c.). Forty five minutes after injection, doses of the peptide producing catalepsy (s.c., 8.3-14.2 micromol kg(-1), i.c.v., 360 nmol) significantly reduced respiratory frequency and volume of rats breathing air and blocked the hypercapnic ventilator response of rats breathing from 4% to 10% CO2. I.c.v. administration of [1-5]dermorphin and [1-4]dermorphin (from 36 to 360 nmol) never stimulated respiration but significantly reduced basal and CO2-stimulated ventilation. Opioid respiratory depression was only antagonized by naloxone. 3. In awake rats, [Lys7]dermorphin (0.1-1 mg kg(-1), s.c.) decreased blood pressure. This hypotensive response was abolished by naloxone, reduced by naloxone methyl bromide and unaffected by naloxonazine. 4. In conclusion, the present study indicates that analgesic doses of [Lys7]dermorphin stimulate respiration by activating central mu1 opioid receptors and this respiratory stimulation involves a forebrain 5-hydroxytryptaminergic excitatory pathway.
Analgesia↗
Glycodermorphins: opioid peptides with potent and prolonged analgesic activity and enhanced blood-brain barrier penetration.
1. In order to improve the in vivo stability of the opioid peptide dermorphin we synthesized O-betaglucosylated analogs ([Ser7-O-betaGlc]dermorphin and [Ser7-O-betaGlc(Ac)4]-dermorphin) and C-alphagalactosylated analogs ([Ala7-C-alphaGal]dermorphin and [Ala7-C-alphaGal(Ac)4]-dermorphin). 2. O- and C-glycosylation of dermorphin halved the peptide affinity for brain mu-opioid receptors and the biological potency in guinea-pig ileum assay (GPI). Despite their lower opioid receptor affinity, when administered intracerebroventricularly (i.c.v., 8-40 pmol) and subcutaneously (s.c., 0.5-3 micromol kg(-1)) in rats, glycosylated analogs were two times more potent than dermorphin in reducing the nociceptive response to radiant heat. Acetylation of sugar hydroxyl groups reduces 5-10 times both biological activity on GPI and mu-receptor affinity, whereas the antinociceptive potency was equal to (i.c.v.) or only two-three times lower (s.c.) than dermorphin potency. 3. Blood-Brain Barrier Permeability Index (BBB-PI) of the glycodermorphins was significantly higher than that of dermorphin, indicating a facilitated entry into the brain: O-beta-linked glucoconiugates are expected to enter CNS by the glucose transporter GLUT-1 of the endothelial barrier. However the calculated BBB-PI for the C-alphagalactoside was about two times higher than that of the O-betaglucoside, excluding the implication of GLUT-1 that is known to be selective for O-beta-links and preferring for the exose glucose. 4. The enhanced brain permeability with the subsequent decrease in peripheral dosage of these opioid peptides did not result in lowering constipation.
Amino Acid Sequence↗
Deltorphin transport across the blood-brain barrier.
In vivo antinociception studies demonstrate that deltorphins are opioid peptides with an unusually high blood-brain barrier penetration rate. In vitro, isolated bovine brain microvessels can take up deltorphins through a saturable nonconcentrative permeation system, which is apparently distinct from previously described systems involved in the transport of neutral amino acids or of enkephalins. Removing Na+ ions from the incubation medium decreases the carrier affinity for deltorphins (-25%), but does not affect the Vmax value of the transport. The nonselective opiate antagonist naloxone inhibits deltorphin uptake by brain microvessels, but neither the selective delta-opioid antagonist naltrindole nor a number of opioid peptides with different affinities for delta- or mu-opioid receptors compete with deltorphins for the transport. Binding studies demonstrate that mu-, delta-, and kappa-opioid receptors are undetectable in the microvessel preparation. Preloading of the microvessels with L-glutamine results in a transient stimulation of deltorphin uptake. Glutamine-accelerated deltorphin uptake correlates to the rate of glutamine efflux from the microvessels and is abolished by naloxone.
Animals↗
Immunomodulatory responses to delta-opioid receptor ligands in human lymphocytes.
In phytohemagglutinin (PHA) activated human peripheral blood mononuclear cells. [3H]thymidine uptake and interferon gamma production were increased by the delta-opioid receptor agonist, deltorphin-I (10(-14)-10(-10) M) and by the delta-opioid antagonist naltrindole (10(-13)-10(-9) M). Combination of 10-9 M naltrindole with deltrophin-I (10(-12)-10(-8)M) significantly inhibited the proliferative response but did not affect interferon production.
Analgesics, Opioid↗
Postnatal development of delta-opioid receptor subtypes in mice.
1. The density and affinity of binding sites for the delta-selective opioid ligands [3H]-[D-Ala2, Asp4]deltorphin (DELT-I), [3H]-[D-Ala2Glu4]-deltorphin (DELT-II), [3H]-[D-Pen2,D-Pen5]enkephalin (DPDPE), and [3H]-naltrindole (NTI) were determined in whole brain from 10, 15, 25 and 60 day-old C57BL mice. 2. At all ages, the analyses of the homologous displacement curves, gave best fits to single rather than to multiple site models. The binding capacity (Bmax) labelled by [3H]-NTI was about one half that labelled by [3H]-DELT-I, [3H]-DELT-II and [3H]-DPDPE. In 25 and 60 day-old mouse brain the DPDPE Bmax was 25% less than the deltorphin-II Bmax. 3. In saturation experiments, specific binding of [3H]-DELT-I on adult mouse brain homogenates was best fitted by a two-site model (34%, high affinity site, Kd = 1.08 nM and 66% low affinity sites, Kd = 39.9 nM). 4. DPDPE produced a biphasic inhibition of specific [3H]-DELTI-I binding, from 15 days of age onwards. The relative percentage of high and low affinity sites was 72% and 28% in 15 day-, 65% and 35% in 25 day- and 30% and 70% in 60 day-old mice. 5. In adult mouse brain labelled with [3H]-DELT-I, DELT-II recognized 71% of high-affinity and 29% of low-affinity sites DELT-I and DPDPE produced monophasic inhibition of specific [3H]-DELT-II binding to brain homogenates of adult mice. 6. These data suggest that a sub-population of delta-sites (probably the delta 2-subtype), recognized by DELT-I, with high affinity for DELT-II and low affinity for DPDPE develops from 25 days onward. 7. In electrically stimulated mouse vas deferens (MVD) the rank order of potency of the three delta-agonists was: DELT-I > DELT-II > DPDPE in 10 day-old mice: and DELT-I- DELT-II > DPDPE, from 25 days onward. During this time, the potency of DELT-II increased about 15 fold whereas the potency of DELT-I and DPDPE increased only 5 times. The higher efficacy of DELT-II could depend on receptor maturation towards the delta 2-subtype.
Animals↗
Is transrectal ultrasonography a reliable diagnostic approach in ejaculatory duct sub-obstruction?
We studied the diagnostic predictive power of transrectal ultrasonography (TRUS) coupled with semen volume in cases of distal seminal tract sub-obstruction. As a gold standard for diagnosis we used seminal tract washout (STW). Non-azoospermic subjects (n = 112) were submitted to transrectal ultrasonography because of suspected excretory infertility or other andrological pathologies, before performing STW. STW indicated ejaculatory duct sub-obstruction in 36.6% of the patients. Seminal vesicle enlargement (anterior-posterior diameter > or = 15 mm) and seminal vesicle roundish anechoic areas (stasis) were the ultrasonographic anomalies more often associated with ejaculatory duct sub-obstruction. Stepwise logistic regression (SLR) analysis revealed that the ultrasonographic evidence of stasis was highly diagnostic only in the presence of a low semen volume (< or = 1.5 ml) and that ejaculatory duct sub-obstructions may be present but with no evidence of ultrasonographic anomalies. Therefore, TRUS is a useful approach for the treatment of suspected ejaculatory duct sub-obstruction, but is not a reliable diagnostic tool and, before performing transurethral surgery, STW should be mandatory.
Adult↗
Biliopancreatic diversion with transitory gastroplasty preserving duodenal bulb: 3 years experience.
BACKGROUND: The authors have performed 521 bariatric surgery operations (319 restrictive procedures and 202 malabsorptive procedures). METHODS: During the last few years we have introduced an evolution of biliopancreatic diversion (BPD): BPD with transitory gastroplasty, preserving the duodenal bulb (53 cases). From a technical point of view, the operation consists of a BPD, coupled with a gastroplasty which is transitory due to the use of a polydioxanone (PDS) band. In the last few cases, instead of a VBG (with PDS band) in order to make the operation completely reversible without any suture on the stomach, we made a gastric pouch by banding with PDS calibrated with the same tube as for the Lap-band (20 cc). We maintained completely the duodenal bulb (5 cm from the pylorus), making an end-to-side duodeno-ileal isoperistaltic anastomosis. RESULTS: With this anastomosis, only 2% of patients developed an anastomotic ulcer. With this new procedure, results have been good in terms of weight loss (similar to that of BPD-AHS) and in nutritional complications. No patient has had hypoalbuminemia, diarrhea or halitosis. CONCLUSION: BPD with temporary gastric restriction has provided satisfactory results.
Adult↗
Evaluation of the efficacy of pivagabine on insomnia associated with mood disorders.
The efficacy of a new drug, pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg), was studied on 100 patients affected by insomnia, associated with mood disorders. The pharmacological treatment with 900 mg/d pivagabine produced a significant improvement in the quality of both sleep and awakening. The results shown in the present study were positive and likely attributable to the inhibitory modulating activity of pivagabine on corticotropin releasing factor secretion, that is considered to be responsible for insomnia associated with anxiety or coexisting anxiety and depression, observed in patients with chronic stress. The recovery of sleep physiological structure provokes a significant reduction in the criteria reported in the Self-rating Anxiety Scale (SAS).
Adult↗
Antinociceptive and behavioral effects of synthetic deltorphin analogs.
A possible correlation of behavioral, antinociceptive and cataleptic responses with central delta- and mu-opioid receptor stimulation was tested for in the rat by i.c.v. injections of some synthetic deltorphin analogs. At doses ranging from 0.1 to 3.0 nmol/rat, the selective delta-opioid receptor agonist, [D-Ala2,Glu4]deltorphin (Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2), induced a dose-dependent stereotyped pattern of locomotor activity, reaching the maximum in the first 30 min; doses higher than 30 nmol induced early and fleeting antinociception. The replacement of Glu4 by Gly, Ala, Val, His or Asn yielded peptides with a lower delta-selectivity because of a gain in mu-affinity. [D-Ala2,Ala4]deltorphin (0.14-4.0 nmol) induced negligible behavioral stimulation but a rapidly appearing and long-lasting analgesia and catalepsy. The other four synthetic peptides induced biphasic effects: low dosages stimulated locomotion whereas higher doses initially suppressed, then increased locomotor activity. At doses ranging from 1 to 70 nmol all the peptides induced analgesia and catalepsy. In experiments examining the locomotor and antinociceptive effects induced by 14 nmol of [D-Ala2,Gly4]deltorphin in rats pretreated with mu and delta antagonists, the non-selective mu-opioid receptor antagonist, naloxone (1 mg/kg i.p.), reduced analgesia and abolished the initial hypolocomotion. The delta-selective antagonist, naltrindole (10 mg/kg i.p.), abolished locomotor activity without affecting analgesia. The mu1 -selective antagonist, naloxonazine (10 mg/kg i.v.), seemed to prolong analgesia and immobility. Hence this peptide appears to activate, in addition to delta-receptors, mainly the opioid receptor mu2-subtype, which mediates catalepsy in the rat. We suggest that the mu2- and delta-opioid receptors of the rat brain modulate locomotor behavior by activating functionally opposed responses. [D-Ala2,Ala4]deltorphin had an antinociceptive and cataleptic potency higher than would have been expected from its mu-affinity. A possible explanation might be a mu/delta-opioid receptor interaction.
Analysis of Variance↗
Microinsemination techniques for the treatment of patients suffering agenesia of the vas deferens.
Thirty cycles of microsurgical epididymal sperm aspiration were performed on 27 patients presenting agenesia of the vas deferens. Two techniques of microinsemination were used, depending on the quality of the sperm preparation: subzonal sperm microinjection and microdroplet insemination. The results obtained by both microinsemination procedures are presented and discussed.
Biopsy↗
The dermorphin peptide family.
1. In 1980, the skin of certain frogs belonging to the genus Phyllomedusinae was found to contain two new peptides that proved to be selective mu-opioid agonists. Given the name dermorphins, these were the first members of a peptide family that in the past 15 years has grown to reach a total of seven naturally occurring peptides and nearly 30 synthetic analogs. 2. Dermorphin peptides are potent analgesics in rodents and primates, including man. Some dermorphins can enter the blood-brain barrier and produce central antinociception after peripheral administration. 3. The dermorphin family also includes mu 1-opioid receptor selective agonists that produce intense opioid analgesia, but stimulate pulmonary ventilation. 4. Experiments in rats and mice chronically exposed to dermorphins have shown that not only do they have higher antinociceptive efficacy and potency than morphine, but they are also less likely than morphine to produce tolerance, dependence and opiate side effects.
Analgesics, Opioid↗
Opioid receptor affinity and analgesic activity of O- and C-glycosylated opioid peptides.
O- and C-glycosylation of the mu-agonist dermorphin reduced neither its mu receptor affinity in binding assay nor its agonist potency in guinea-pig ileum assay (GPI). O- and C-glycosylation of the delta-agonist deltorphin reduced its delta-receptor affinity and its agonist potency in mouse vas deferens assay (MVD). O- and C-glycosylated dermorphin, administered i.c.v. and s.c., produced long-lasting antinociception in mice and rats. The ratio between i.c.v. and s.c. antinociceptive ED50 demonstrates facilitated transport into the CNS only for the galactosil peptide. Acetylation significantly reduced penetration of glycopeptides into the CNS indicating that facilitated transport into the CNS exists, but does not depend on the glucose transporter (GLUT-1).
Analgesics, Opioid↗
Production of antinociception by peripheral administration of [Lys7]dermorphin, a naturally occurring peptide with high affinity for mu-opioid receptors.
1. The opioid activity of the amphibian peptide, [Lys7]dermorphin, was studied in rats and mice. When administered intracerebroventricularly (i.c.v.), intravenously (i.v.) or subcutaneously (s.c.) it produced a long lasting analgesia. Its antinociceptive potency exceeded that of morphine 290 times by i.c.v. injection, and 25-30 times by peripheral administration. 2. The dose-response curves of [Lys7]dermorphin antinociception were shifted to the right by the pretreatment with naloxone (0.1 mg kg-1, s.c.) or with the mu 1-selective antagonist, naloxonazine (10 mg kg-1, i.v. 24 h before peptide injection). 3. The peptide also displayed potent antinociceptive effects in a chronic inflammatory pain model (rat Freund's adjuvant arthritis). In this pain model, systemic administration of the peptide raised the nociceptive threshold more in inflamed than in healthy paw. 4. High central and peripheral doses of [Lys7]dermorphin in rats produced catalepsy. The cataleptic response was antagonized by naloxone but left unchanged by naloxonazine pretreatment. 5. In rats and mice, central or peripheral administration of [Lys7]dermorphin induced a significantly slower development of tolerance to the antinociceptive effect than did morphine. 6. Upon naloxone precipitation of the withdrawal syndrome, [Lys7]dermorphin-dependent mice made fewer jumps and lost less weight than the morphine-dependent animals. Withdrawal hyperalgesia did not develop in [Lys7]dermorphin-dependent mice. 7. In conclusion, [Lys7]dermorphin seems to be a unique opioid peptide having a high penetration into the blood-brain barrier despite its low lipid solubility. This peptide causes fewer side-effects than other opioids and appears less likely than morphine to cause physical dependence in rats and mice.
Analgesics, Opioid↗