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71.
Andrew D. Medhurst Gerd E. K. Novotny Stephen G. Parker Nicola M. Deighton Alberto J. Kaumann 《Naunyn-Schmiedeberg's archives of pharmacology》1993,347(3):257-265
Summary To investigate whether 5-HT1-like receptor-mediated inhibition of adenosine 3 : 5-cyclic monophosphate (cyclic AMP) accumulation occurs in nerves or smooth muscle of saphenous vein, infusions of 6-hydroxydopamine (6-OHDA) were administered to dogs with the aim of inducing sympathetic nerve damage. The effects of 6-OHDA on other 5-HT1-like receptor-mediated responses at the pre- and post-junctional level were investigated for comparison by studying 5-hydroxytryptamine (5-HT)-induced inhibition of 3H-noradrenaline release and contraction of smooth muscle respectively.Disruption of nerve function by 6-OHDA was revealed by the lack of catecholaminergic fluorescence and neurogenic contractile responses in saphenous veins from dogs treated with 6-OHDA. In addition, severe impairment of neuronal uptake mechanisms were apparent since basal efflux of 3H-noradrenaline, electrically-evoked release of 3H-noradrenaline and remaining 3H-noradrenaline content were considerably reduced. Some 3H-noradrenaline was taken up and released in 6-OHDA treated tissues which is consistent with the existence of nerve varicosities resistant to the present dosing regime of 6-OHDA, an observation substantiated by electron microscopy studies showing inconsistent lesions of nerve terminals.6-OHDA pre-treatment potentiated the smooth muscle contractile responses mediated by 5-HT1-like receptors as well as potentiating 5-HT-evoked inhibition of prostaglandin E2-stimulated cyclic AMP accumulation. It did not, however, affect 5-HT-induced inhibition of 3H-noradrenaline release. The present results suggest that inhibition of cyclic AMP accumulation by 5-HT occurs predominantly in smooth muscle.
Correspondence to A. J. Kaumann at the above address 相似文献
72.
Nicola J Jordan Malcolm L Watson Robert J Williams Alan G Roach Teizo Yoshimura John Westwick 《British journal of pharmacology》1997,122(4):749-757
- The production of chemokines by vascular smooth muscle cells (SMC) is implicated in the pathogenesis of atherosclerosis, although the factors regulating chemokine production by these cells are incompletely characterized.
- We describe the differential stimulation of interleukin-(IL)-8, monocyte chemoattractant protein (MCP)-1 and regulated on activation normal T-cell expressed and secreted (RANTES) synthesis following treatment of human vascular SMC with IL-1α or tumour necrosis factor α (TNFα). Under basal conditions, cultured SMC release very low amounts of IL-8, MCP-1 and RANTES as assessed by specific ELISA. Concentration-response studies with IL-1α or TNFα revealed that each stimulus induced a similar amount of MCP-1. In contrast approximately three fold more IL-8 was induced by IL-1α than by TNFα whereas significant RANTES production was induced only by TNFα. These findings point to a divergence in the regulation of synthesis of the different chemokines in response to IL-1α or TNFα stimulation.
- The T-cell derived cytokines IL-10 and IL-13 were also found to have differential effects on chemokine production by SMC. IL-13, but not IL-10, significantly enhanced IL-8 and MCP-1 release in response to IL-1α or TNFα. This increase in chemokine release appeared to be accounted for by increased mRNA expression.
- These findings provide support for the concept that smooth muscle cells can have an active role in a local immune response via the production of chemokines which can be selectively modulated by T-cell derived cytokines.
73.
Dr. Maurizio Vaglini MD Dr. Filiberto Belli MD Mario Santinami MD Flavio Arienti MD Giorgio Parmiani MD Laura Persiani MD Nicola Santoro MD Maria Grazia Inglese MD Fortunato D'Elia MD Natale Cascinelli MD 《Annals of surgical oncology》1995,2(1):61-70
Background: Therapies of advanced melanoma patients with interleukin-2 (IL-2) and cytotoxic lymphocytes have produced interesting results, but a larger diffusion of these treatments is limited by the severe side effects due to IL-2 systemic infusion. A strictly regional administration of IL-2 and cells by an isolation perfusion (IP) in extracorporeal circulation (ECC) for the treatment of regional melanoma metastases could improve tolerability and efficacy of this specific modality of immunotherapy.
Methods: Ten patients were submitted to adoptive immunotherapy with IL-2 and lymphokine-activated killer (LAK) cells by IP in ECC. The schedule of treatment included the first course of a 5-day systemic administration of IL-2 (Proleukin, EuroCetus 9–12 × 106 IU/M2/day continuous infusion); autologous LAK cells were obtained via leukapheresis and after in vitro activation were given (range 8–28 × 109) along with IL-2 (120-2,400 IU/ml of perfusion priming) to the affected limb by IP; IL-2 (9–12×106 IU/m2/day) was also administered by systemic continuous infusion for 5 days starting on the day after IP.
Results: All patients concluded the treatment without any major local or systemic toxicities. Clinical responses included one complete and six partial remissions; three patients had stable disease. All patients are alive. Follow-up after IP ranged from 12 to 35 months (median: 22). The analysis of circulating lymphocytes revealed the rapid disappearance of LAK cells, suggesting their extravasation and/or endothelial adhesion in perfused tissues.
Conclusions: IP with IL-2 and LAK cells is a new approach for the treatment of in-transit metastases due to cutaneous melanoma. The treatment appears to be feasible and reliable. Further biological and immunological studies should permit amelioration of the present modality of treatment. 相似文献
74.
Friedman D Cuneo S Valenzano M Marinari GM Adami GF Gianetta E Traverso E Scopinaro N 《Obesity surgery》1995,5(3):308-313
Background: 239 pregnancies occurred in 1136 women who had undergone biliopancreatic diversion (BPD). Methods: There were
73 abortions, and 14 pregnancies are presently in their course. The 152 term pregnancies (six twins) occurred in 129 women
2-173 months (mean 42.7) after BPD. Mean age and current excess weight were 31.4 years (20-42) and 29.1% (-6.9-78.2), and
mean excess weight loss was 72.9% (30.4-110.5). Results: Mean weight gain during pregnancy was 6.2 kg (-21-25). In 32 patients
(21%), parenteral nutritional support was needed. In all the other patients (79%), the usual supplementations were given.
Of the newborns, 122 were delivered at term (84.7%) with a mean weight of 2842.4 g (1760-4600 g) and a mean length of 48.5
cm (43-59 cm), while the 22 preterm babies (15.3%) weighed 2151.1 g (1400-3850 g) and had a length of 44.6 cm (33-56 cm).
Forty infants (27.8%) were small for gestational age but 17 of them weighed more than 2500 g. Eleven twins (one abortion at
26th week) were also delivered, with a mean weight of 2088.6 g (1200-3100 g) and a mean length of 45.6 cm (35-50 cm). Delivery
was spontaneous in 85 instances (56%), while vacuum extractor was used in one, and 66 cesarean sections were performed. There
were two birth malformations, one infant died after surgery for meconium obstruction and two died from unknown causes. Of
the 129 women, 35 had been infertile before BPD. Conclusions: Disappearance of infertility and decrease of pregnancy risk
are to be considered among the beneficial effects of weight reduction following BPD. 相似文献
75.
Varrassi G Marinangeli F Agrò F Aloe L De Cillis P De Nicola A Giunta F Ischia S Ballabio M Stefanini S 《Anesthesia and analgesia》1999,88(3):611-616
We assessed the relative morphine consumption in a combined analgesic regimen (on-demand morphine plus the nonopioids propacetamol or ketorolac) after gynecologic surgery. Two hundred women randomly received two i.v. doses of propacetamol 2 g or ketorolac 30 mg in a double-blinded, double-dummy trial. Patients were monitored for 12 h, and the following efficacy variables were assessed: total dose of morphine, pain intensity, and global efficacy. Safety and tolerability were evaluated by the occurrence of adverse events, especially the presence and intensity of gastrointestinal symptoms. Hemostatic variables were measured 30 and 60 min after the first infusion; arterial blood pressure, heart and respiratory rates, sedation scores, and renal and hepatic function were also assessed. Total morphine requirements were not significantly different between the propacetamol (10.6 +/- 4.8 mg) and ketorolac (10.2 +/- 4.4 mg) groups. The evolution of pain intensity and the global efficacy also showed similar patterns in the two groups: 70.2% of patients in the propacetamol group rated the efficacy as "good/ excellent" compared with 68.2% in the ketorolac group. There were no clinically significant changes in vital signs or laboratory values and no observed differences between the two groups, although ketorolac slightly, but not significantly, prolonged the bleeding time. Epigastric pain was present in 9% and 15% of patients receiving propacetamol and ketorolac, respectively. There were two adverse events in the propacetamol group and four in the ketorolac group. Propacetamol demonstrates an efficacy similar to that of ketorolac and has an excellent tolerability after gynecologic surgery. IMPLICATIONS: Propacetamol and ketorolac, combined with patient-controlled analgesia morphine, show similar analgesic efficacy after gynecologic surgery. Morphine consumption and pain scores were comparable in the two studied groups. Propacetamol is as effective as ketorolac and has an excellent tolerability after gynecologic surgery. 相似文献
76.
A multifactorial etiology underlies the majority of cases of Alzheimer's disease (AD). Both ill-defined environmental and genetic factors contribute to the development of the disease. Allele epsilon 4 of ApoE is a genetic risk factor. Its presence increases the risk of developing AD. However, presence of e4 is neither necessary nor sufficient for the disease to arise. Apart from the common multifactorial forms of the disease, there are rare variants which are inherited as Mendelian traits. To date three genes are known that can be mutated in these rare forms of AD. Of these, mutations in the gene presenilin 1 on chromosome 14 are most frequent. In addition, mutations in the gene presenilin 2 on chromosome 1 and in the amyloid precursor protein gene (APP on chromosome 21) occur in autosomal dominant AD. This article reviews our present knowledge of the genetics of AD and discusses its relevance for patients with AD and their relatives. 相似文献
77.
78.
Pietra N Sarli L Maccarini PU Sabadini G Costi R Gobbi S 《World journal of surgery》2000,24(3):345-352
Consensus has never been reached regarding the need or the imaging technique for evaluating the common bile duct (CBD) in
patients considered for cholecystectomy. With the advent of laparoscopic cholecystectomy there has been a resurgence of interest
in the role of preoperative intravenous cholangiography (IVC) as an alternative for evaluating the CBD. The purpose of this
audit was to assess whether a diagnostic workup based on IVC, which permits selective use of intraoperative cholangiography
(IOC) and endoscopic treatment of CBD stones before surgery, could be useful in patients undergoing laparoscopic cholecystectomy
(LC). In patients without jaundice, gallstone pancreatitis, a prior diagnosis of CBD stones, a prior history of contrast allergy,
or a risk of contrast-associated acute renal failure, IVC was performed routinely. Patients suspected to have CBD stones based
on IVC results or with inconclusive IVC and patients with a strong clinical suspicion of CBD stones were referred for endoscopic
retrograde cholangiography (ERC). IOC was carried out in patients who had a history of contrast allergy or risk of contrast-associated
acute renal failure and whenever the surgeon was in doubt as to the biliary anatomy or CBD clearance. IVC was carried out
in 1155 patients, ERC in 225, and IOC in 54. IVC was conclusive in 1132 patients, with a diagnostic accuracy of 99%. Our workup
permitted the sequential endoscopic-laparoscopic treatment of cholecystocholedocholithiasis in 162 cases. During the follow-up
period residual CBD stones were detected in four patients. Our diagnostic workup showed that routine IVC exposes the population
to a large radiation burden, and the cost is high for the small number of patients who benefit. Moreover, it does not seem
helpful in reducing the incidence of CBD injuries during LC. 相似文献
79.
Rebecca J Dearman Catherine J Betts Neil Humphreys Brian F Flanagan Nicola J Gilmour David A Basketter Ian Kimber 《Toxicological sciences》2003,71(2):137-145
Chemical respiratory allergy is an important occupational health problem, but there are currently available no validated methods for hazard identification. This is due in part to the fact that the relevant cellular and molecular mechanisms of sensitization of the respiratory tract have been unclear, with particular controversy regarding the role of IgE. There is now increasing evidence that respiratory sensitization is associated with the preferential activation of type 2 T lymphocytes and the expression of type 2 cytokines interleukin (IL)-4, IL-5, IL-10, and IL-13. Type 2 cell products favor immediate type hypersensitivity reactions, serving as growth and differentiation factors for mast cells and eosinophils, the cellular effectors of the clinical manifestations of the allergic responses, and promoting IgE antibody production. There has been considerable interest in the application of cytokine profiling for the characterization of chemical allergens, with cytokine phenotypes analyzed in freshly isolated tissue, or following culture in the presence or absence of mitogen at the level of protein secretion or mRNA expression. Experience to date suggests that the measurement of induced cytokine secretion profiles shows promise for the hazard identification and characterization of chemical respiratory allergens. The purpose of this brief review article is to consider the approaches available and to highlight key procedural issues. 相似文献
80.
Sabbatini M Sansone G Uccello F De Nicola L Nappi F Andreucci VE 《Transplantation》2000,69(9):1946-1990
The acute effects of cyclosporin (CsA, 20 mg(kg i.v.) and rapamycin (RAPA, 5 mg(kg i.v.) on glomerular dynamics were separately investigated by renal micropuncture in two groups of intact rats (group CsA and RAPA, respectively) and compared with vehicle-treated rats, used as controls (group CON). Left kidney glomerular filtration rate (GFR) was decreased by CSA (-35% vs. CON, P<0.05), but was not affected by RAPA (-14% vs. CON, NS), whereas the single-nephron GFR (SNGFR) was significantly decreased in both groups (-40% in CsA, P<0.01 and -26% in RAPA, P<0.05 vs. CON). In both groups glomerular plasma flow (GPF) was significantly reduced vs. CON (CsA: -48%, and RAPA: -25%) due to the increase in both afferent (Ra) and efferent (Re) glomerular resistances: group CSA showed a prevalent rise in Re (+98% vs. CON, P<0.001) than in Ra (+66%, P<0.001); in group RAPA the increment was modest and similar in Ra and Re (+33 and +32%, respectively, NS versus CON). A further group of rats was studied in which L-Arginine (ARG), the precursor of nitric oxide (NO), was administered (2.5 mg/Kg/min iv) with RAPA (group ARG). ARG limited the rise in Ra and Re, thereby preserving GPF; nevertheless, SNGFR remained low (-26% vs. CON, P<0.05) due to the decrease in the effective filtration pressure (-26% vs. CON). These data demonstrate that: (1) CsA is nephrotoxic at immunosuppressive doses; (2) RAPA, even at huge doses, has marginal effects on renal and glomerular dynamics; (3) the ARG-NO pathway is only partially involved in the vasoconstriction of superficial nephrons after RAPA administration. 相似文献