Background: Ketamine has been shown to suppress platelet aggregation, but its mechanisms of action have not been defined. The purpose of the current study is to clarify the effects of ketamine on human platelet aggregation and to elucidate the underlying mechanisms of its action.
Methods: Platelet aggregation was measured using an eight-channel aggregometer, and cytosolic free calcium concentration was measured in Fura-2/AM-loaded platelets using a fluorometer. Inositol 1,4,5-triphosphate (IP3) was measured with use of a commercially available IP3 assay kit. To estimate thromboxane A2 (TXA2) receptor binding affinity and expression, Scatchard analysis was performed using [3H]S145, a specific TXA2 receptor antagonist. TXA2 agonist binding assay was also performed. The membrane-bound guanosine 5'-triphosphatase activity was determined using [[gamma]-32P]guanosine triphosphate by liquid scintillation analyzer.
Results: Ketamine (500 [mu]m) suppressed aggregation induced by adenosine diphosphate (0.5 [mu]m), epinephrine (1 [mu]m), (+)-9,11-epithia-11,12-methano-TXA2 (STA2) (0.5 [mu]m), and thrombin (0.02 U/ml) to 39.1 +/- 30.9, 46.3 +/- 4.3, -2.0 +/- 16.8, and 86.6 +/- 1.4% of zero-control, respectively. Ketamine (250 [mu]m-1 mm) also suppressed thrombin- and STA2-induced cytosolic free calcium concentration increase dose dependently. Although ketamine (2 mm) had no effect on TXA2 receptor expression and its binding affinity, it (1 mm) suppressed intracellular peak IP3 concentrations induced by thrombin and STA2 from 6.60 +/- 1.82 and 4.39 +/- 2.41 to 2.41 +/- 0.98 and 1.90 +/- 0.86 pmol/109 platelets, respectively, and it suppressed guanosine triphosphate hydrolysis induced by thrombin (0.02 units/ml) and STA2 (0.5 [mu]m) to 50.3 +/- 3.2 and 67.5 +/- 5.5%versus zero-control, respectively. 相似文献
This study was designed to determine the influence of ileal pouch capacity and anal sphincteric function on the clinical outcome
after ileal pouch-anal anastomosis. A total of 24 patients who had undergone ileal pouch-anal anastomosis (J pouch) for ulcerative
colitis were studied. The 24-hour stool frequency was found to be inversely correlated with the sensitivity threshold volume
(STV), maximal tolerance volume (MTV), and distensibility, but was independent of the maximal resting pressure and maximal
squeeze pressure. Patients experiencing nocturnal fecal incontinence had maximal resting pressures that were significantly
lower than those of nocturnally continent patients. Among the patients with fecal incontinence, those with frequent soiling
had lower resting pressures, STV, and distensibility than the patients with intermittent spotting. In addition, the STV in
patients needing nocturnal evacuation were lower than those of patients who did not evacuate after falling asleep. The conclusions
are as follows. Both stool frequency and the need for nocturnal pouch evacuation correlated directly with pouch volume. Anal
incontinence was more common in patients with low internal sphincteric function. In addition, frequent and gross nocturnal
incontinent patients demonstrate a worse function in both the anal sphincter and reservoir than those with intermittent spotting. 相似文献
Based upon detailed dissections of the lymphatic system in adult cadavers, the lymphatic drainage of the gallbladder was divided
into three pathways: (1) The cholecystoretropancreatic pathway, which had two routes, one running spirally from the anterior
surface of the common bile duct to the right rear, and the other running almost straight down from the posterior surface of
the common bile duct. These routes converged at the principal retroportal node at the posterior surface of the head of the
pancreas. (2) The cholecysto-celiac pathway; this was the route running to the left through the hepatoduodenal ligament to
reach the celiac nodes. (3) The cholecysto-mesenteric pathway; this was the route running to the left in front of the portal
vein to connect with the nodes at the superior mesenteric root. The cholecysto-retropancreatic pathway can be regarded as
the main pathway, and the principal retroportal node appeared to be critical as the main terminal node in the visceral lymphatic
system of the gallbladder. These three pathways converged with the abdomino-aortic lymph nodes near the left renal vein, and
the nodes in the interaortico-caval space were considered to be of particular importance.
Offprint requests to: M. Ito 相似文献
Summary Only one peptide of CD4 (amino acid residues 70–132) among 16 synthetic peptide fragments selectively inhibited HIV-1 replication and HIV-1-induced syncytium formation. Several smaller peptides within this region did not show any activity, except for the peptide (86–132) which showed somewhat lower activity. 相似文献
To improve the outcome of invasive Candida infections, earlier empirical therapy before the establishment of the definitive diagnosis is considered to be necessary. However, appropriate use of empirical therapy for suspected candidiasis in febrile non-neutropenic surgical patients has not been defined. According to the guidelines from the Infectious Diseases Society of America, empirical therapy of suspected candidiasis in this setting should be limited to patients with Candida colonization of multiple sites, multiple other risk factors, and absence of any other causes of fever. A corrected colonization index which takes into account both the density and the degree of colonization of Candida spp. was shown to be the independent factors that predict subsequent candidal infection. It may also be appropriate to commence empirical therapy on the basis of a positive serodiagnostic test. Beta-D glucan is a cell-wall constituent of fungi, which is assumed to be a marker of fungal sepsis. However, it has been shown that beta-D-glucan can also be detected in patients without fungal infections, such as those on haemodialysis, and its positive predictive value is relatively low. The mono-utilization of beta-D-glucan for the assessment of fungal infection should therefore be avoided. The combined assessment of beta-D-glucan and extent of colonization with Candida spp. is believed to have the advantage of lessening the likelihood of a false positive reaction of beta-D-glucan. 相似文献
Our previous study demonstrated that pro-gastrin-releasing peptide(31–98), or ProGRP, is a specific tumor marker in patients with small cell lung carcinoma (SCLC). Using a newly developed, highly sensitive enzyme-linked immunosorbent assay (ELISA) for ProGRP, we analyzed 1,446 samples including those obtained from 478 lung cancer patients to evaluate the clinical usefulness of this ELISA. Several properties indicated that ProGRP is a useful tumor marker for SCLC. First, ProGRP was specifically elevated in SCLC patients. In non-SCLC patients and patients with non-tumorous lung diseases, its serum level was very rarely elevated. Secondly, ProGRP was a reliable marker, in terms of the marked elevation of serum ProGRP levels in SCLC patients. Thirdly, serum ProGRP levels were elevated in SCLC patients even at a relatively early stage of this disease. Fourthly, changes in the serum ProGRP level showed an excellent correlation with the therapeutic responses in SCLC patients. Neuron-specific enolase (NSE) is accepted as a tumor marker of SCLC patients. With the aim of comparing ProGRP and NSE as tumor markers for SCLC patients, we measured serum NSE levels in all samples collected in the present study. We found that ProGRP was superior to NSE in terms of sensitivity, specificity and reliability. Therefore, we consider that ProGRP can play a major role as a clinical tumor marker for SCLC patients. 相似文献
Transganglionic transport of horseradish peroxidase-wheat germ agglutinin conjugate was used to study the central projection of primary afferent neurons innervating facial and intraoral structures. The examined primary neurons innervating the facial structures were those comprising the frontal and zygomaticofacial nerves and those innervating the cornea, while the primary neurons innervating the intraoral structures included those innervating the mandibular incisor and molar tooth pulps and those comprising the palatine nerve. The primary afferents innervating the facial structures project to the lateral or ventral parts of the trigeminal principal, oral and interpolar subnuclei, and to the rostral cervical spinal dorsal horn across laminae I through V, with a greater proportion being directed to the spinal dorsal horn. The primary afferents innervating the intraoral structures terminate in the dorsomedial subdivisions of the trigeminal principal, oral and interpolar subnuclei, and in laminae I, II, and V of the medial medullary dorsal horn, with a much denser projection being distributed to the rostral subnuclei. In addition to the above brain stem trigeminal sensory nuclear complex, they project to the supratrigeminal nucleus, caudal solitary tract nucleus, and paratrigeminal nucleus. These observations agree with previously reported data that the central projection of trigeminal nerve is organized in different manners for the facial and intraoral structures. Furthermore, the present findings in conjunction with our previous studies clarify that the central projection of primary afferents from the facial skin is organized in a clear somatotopic fashion and that the terminal fields of primary afferents from the intraoral structures extensively overlap in the brain stem trigeminal nuclear complex particularly in its rostral subdivisions. The central mechanism of trigeminal nociception is discussed with particular respect to its difference between the facial and intraoral structures. 相似文献