Interleukin-1β-induced, nitric oxide-dependent and -independent inhibition of vascular smooth muscle contraction

Stimulation of vascular smooth muscle by bacterial lipopolysaccharide has been shown to produce interleukin-1β and to induce vasodilation in septic shock. To understand the mechanisms of interleukin-1β-induced relaxation, we examined the effects of interleukin-1β on contractility and cyclic GMP contents of vascular smooth muscle. After treatment of the rat aorta with interleukin-1β (20 ng/ml) for 6 h, the cyclic GMP content increased and the contraction induced by phenylephrine (1 μM) was partially inhibited. An inhibitor of nitric oxide (NO) synthase, N^G-monomethyl-

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-arginine (

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-NMMA, 100 μM), prevented the inhibitory effect of interleukin-1β. After treatment with interleukin-1β for 24 h, the phenylephrine-induced contraction was inhibited more strongly. Neither

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-NMMA (100 μM) nor aminoguanidine (100 μM) reversed the inhibition, whereas methylene blue (10 μM) partially reversed the inhibition. After treatment with interleukin-1β for 12 or 24 h, the cyclic GMP content increased but to a level lower than that obtained with a 6-h treatment. The effects of sodium nitroprusside (1 μM) to inhibit the phenylephrine-induced contraction and to increase the cyclic GMP content were markedly suppressed by the 24-h interleukin-1β treatment. In contrast, the 24-h interleukin-1β treatment did not change the ability of 8-bromo-cGMP to relax the phenylephrine-stimulated aorta. Addition of

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-NMMA (1 mM) during the 24 h treatment prevented NO production and preserved the sodium nitroprusside-induced cGMP generation by interleukin-1β. The 24 h interleukin-1β treatment increased the threshold concentration of KCl needed to induce contraction without changing the maximum contraction. In the presence of 25.4 mM KCl or the non-selective K⁺ channel inhibitor, tetraethylammonium, the inhibitory effect of the 24-h interleukin-1β treatment on phenylephrine-induced contraction was restored. These results suggest that interleukin-1β inhibits vascular smooth muscle contraction by a time-dependent, dual mechanism. After a 6-h treatment with interleukin-1β, the NO/cyclic GMP system is activated. After a 24-h interleukin-1β treatment, in contrast, the NO/cyclic GMP system may be desensitized and the contraction of vascular smooth muscle is inhibited by another mechanism, possibly membrane hyperpolarization.     

Alterations in the supraspinatus muscle belly with rotator cuff tearing: Evaluation with magnetic resonance imaging

We studied the supraspinatus muscle in patients with full-thickness rotator cuff tearing by analyzing its architecture on magnetic resonance imaging. Forty-six shoulders with rotator cuff tears requiring surgical repair were scanned parallel to the long axis of the supraspinatus muscle. We calculated the ratio of the largest width of the supraspinatus muscle belly to the distance from the greater tuberosity to the proximal end of the supraspinatus muscle. We classified the linear bands in the supraspinatus muscle, variation in its signal intensity, and irregularity and vagueness of its margins. The larger the rotator cuff tear, the more atrophic the supraspinatus muscle became. With increased atrophy, linear bands in the suprosupinotus muscle belly increased, muscle signal intensity became less uniform, and its margins became more irregular and vague.     

Pharmacological effects of concomitant administration of β-adrenoceptor blocker and agonist in normal subjects: characterization by heart rate response to exercise

The effects of a combination regimen of metoprolol and ₁-adrenoceptor agonist denopamine on resting and exercise heart rate have been studied in 10 normal volunteers. Maximal ramp upright bicycle exercise was performed three times at 1-week intervals. Two hours before each exercise test, 5 mg metoprolol plus 20 mg denopamine, 5 mg metoprolol plus a denopamine placebo, or two placebos were orally administered in a double-blind fashion.During exercise after placebo administration, heart rate increased in parallel with the exercise intensity. Compared to the placebo values, resting heart rate was significantly decreased by an average of 10 beats · min^–1 by 5 mg metoprolol, whereas it was not altered by the combination regimen. During exercise, however, both the combination regimen and metoprolol alone showed a significant negative chronotropic effect, decreasing peak exercise heart rate by an average of 14 and 21 beats · min^–1, respectively. Peak oxygen uptake was also significantly decreased by both regimens.We conclude that concomitant administration of 5 mg metoprolol and 20 mg denopamine exerts an effective -adrenoceptor blocking action during exercise but a minimal effect at rest in normal subjects. The combination regimen appears to have a favourable pharmacological profile for -adrenoceptor blocker therapy in patients with chronic heart failure.     

The anti-proliferative effect of proliferating cell nuclear antigen-specific antisense oligonucleotides on human gastric cancer cell lines

The proliferating cell nuclear antigen (PCNA) is a nuclear protein that leads DNA synthesis by the DNA polymerase delta. As the PCNA gene is strongly expressed in invasive gastric cancer cells with high proliferative activity, PCNA is suspected of playing an important role in the proliferation and advancement of gastric cancer. Thus, the effects of antisense oligonucleotides specific for PCNA mRNA were examined in seven gastric cancer cell lines. It was found that treatment with antisense oligonucleotides at concentrations of 10–40 M dose-dependently inhibited the growth of all cell lines; however, random sequence oligonucleotides did not modify the proliferation of any type of cells. These results indicate that PCNA is essential for cell proliferation in gastric cancer cells, and that the growth inhibitory effect results from the inhibition of PCNA gene expression. Therefore, PCNA-specific antisense oligonucleotides may be effective in the treatment of gastric cancer.     

Hepatic arterial infusion chemotherapy using percutaneous catheter placement with an implantable port: assessment of factors affecting patency of the hepatic artery

OBJECTIVE: To assess the factors affecting patency of the hepatic artery during hepatic arterial infusion chemotherapy (HAIC) with an implantable port system inserted percutaneously. PATIENTS AND METHODS: Ninety patients with malignant hepatic tumours were given HAIC using percutaneous catheter placement. An end-hole catheter was inserted into the hepatic artery (conventional method) in 41 patients. An end-closed and side-hole catheter was used in 49 patients, in which the catheter tip was fixed in the gastroduodenal artery and the side hole was placed in the common hepatic artery (fixed catheter-tip method). The patency of the hepatic artery was evaluated with computed tomography (CT) arteriography using the implantable port system and angiography. Then, the factors affecting hepatic arterial patency were analysed. RESULTS: Hepatic arterial occlusion was observed in 15 patients (17%). The overall patency of the hepatic artery was 86.9%, 78.4% and 51.5% at 6 months, 1 year and 2 years, respectively. The patency rate of the hepatic artery was significantly higher in patients with catheter placement using fixed catheter-tip method than those using conventional method (P = 0.01), and in patients without transcatheter arterial chemoembolization (TACE) prior to catheter placement than those with prior TACE (P = 0.01). When the variables affecting patency of the hepatic artery were studied together by multivariate analyses, the important factors were the method of catheter placement and the presence or absence of prior TACE. CONCLUSION: We consider that it is important for long-term patency of the hepatic artery during HAIC to use fixed catheter-tip method for percutaneous catheter placement instead of conventional method, and to select patients without prior TACE.     

Insertion of the patella tendon after prosthetic replacement of the proximal tibia

We describe the technique and the results of a method to reconstruct the patellar tendon insertion to a tumor prosthesis by wrapping an artificial mesh around the prosthesis, followed by suturing the patellar tendon and a gastrocnemius flap to the mesh.     

Non-invasive continuous hemodynamic measurement during operation for a child with coarctation of aorta

For non-invasive hemodynamic monitoring, DYNEMO 3000 (SOMETEC Inc) has a 10 mHz ultrasonic echo scan and a 5 mHz Doppler velocimeter connected to an echo-oesophageal probe allowing continuous measurement of the aortic diameter and of the blood flow velocity in the descending aorta. This device thus can only measure the aortic blood flow, but also calculate the stroke volume and the systemic vascular resistance. Moreover, the systolic time intervals and the length of the pre-ejection period can be measured with the oscillometric tensiometer and the electrocardiography. This paper describes a case in which this device was used for a child with coarctation of the aorta. The hemodynamic changes were measured continuously during coarctectomy. During the temporary bypass, the aortic blood flow and the stroke volume decreased, but on the other hand, the total vascular resistance increased at the same time. After the bypass, these parameters returned to the values before the bypass. We think that this device is useful as a non-invasive monitor to observe the hemodynamic changes continuously during operation for a child with congenital heart disease.     

Bone mineral density of the shoulder joint in frozen shoulder

The purpose of this study was to evaluate the osteopenia in several parts of the shoulder joint in a series of individuals suffering from frozen shoulder and to elucidate the pathogenesis. The bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA). In 30 cases of frozen shoulder, 16 men and 14 women, BMD of the head of the humerus, greater tubercle of the humerus, surgical neck of the humerus, and neck of the scapula was evaluated. The average age of the male patients was 58.4 years and of the women, 59.5 years. At the neck of the scapula, there were no significant differences in any of the cases. However, there was a marked decrease in BMD at the proximal end of the humerus on the affected side of women. In contrast, men showed no significant difference between the affected and unaffected shoulders, suggesting that the degree of osteopenia remains low compared with women. Although frozen shoulder is a disease which may occur in both men and women, the loss of bone was conspicuous only in women. This may be due to the involvement of female hormones in alterations of bone in frozen shoulder, as in cases of osteoporosis, in addition to the originally low bone density in women. The degree of osteopenia of the proximal humerus with frozen shoulder was not correlated with the duration of the disease, range of motion of the shoulder joint, or patient's age.     

Primary anorectal malignant melanoma: Report of a case

(Received for publication on Aug. 18, 1997; accepted on May 15, 1998)     

An angiographically occult arteriovenous malformation in the medial parietal lobe presenting as seizures of medial temporal lobe origin

We present an unusual case of a patient who was diagnosed with temporal lobe epilepsy and whose seizures were reduced markedly after excision of an angiographically occult arteriovenous malformation (AVM) located in the left medial parietal lobe. A 38-year-old man had complex partial seizures characterized by motionless staring with oroalimentary and behavioral automatisms since the age of 15 years. Magnetic resonance imaging (MRI) demonstrated a small lesion extending from the left posterior cingulate gyrus to the precuneus. There was no MRI evidence of mesial temporal sclerosis. Intracranial EEG recordings showed ictal onset from the left medial parietal lobe propagating to the medial temporal lobes. Clinical signs appeared when these discharges reached the temporal lobes. After excision of the lesion (which was histologically confirmed as an AVM), together with the marginal cortex, seizures were reduced significantly. Careful diagnostic evaluation of lesions such as the this one may reveal an epileptogenic lesion (zone) far from the region where scalp ictal discharges seem to arise. In our case, we hypothesize that false localization was due to propagation of ictal discharges from the parietal focus through the limbic system.