Oligonucleotide-targeting periostin ameliorates pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a median survival of 3-4 years after diagnosis. It is the most frequent form of a group of interstitial pneumonias of unknown etiology. Current available therapies prevent deterioration of lung function but no therapy has shown to improve survival. Periostin is a matricellular protein of the fasciclin 1 family. There is increased deposition of periostin in lung fibrotic tissues. Here we evaluated whether small interfering RNA or antisense oligonucleotide against periostin inhibits lung fibrosis by direct administration into the lung by intranasal route. Pulmonary fibrosis was induced with bleomycin and RNA therapeutics was administered during both acute and chronic phases of the disease. The levels of periostin and transforming growth factor-ß1 in airway fluid and lung tissue, the deposition of collagen in lung tissue and the lung fibrosis score were significantly reduced in mice treated with siRNA and antisense against periostin compared to control mice. These findings suggest that direct administration of siRNA or antisense oligonucleotides against periostin into the lungs is a promising alternative therapeutic approach for the management of pulmonary fibrosis.

Nerve conduction study of human tetrodotoxication.

We carried out serial nerve conduction studies in a patient with tetrodotoxication caused by ingesting pufferfish. Conduction velocities and amplitudes of muscle and sensory nerve action potentials were equally affected. Neither temporal dispersion nor focal conduction block occurred. The proximal (F wave) motor latencies were also prolonged. These abnormalities rapidly improved in parallel with clinical recovery and with the decrease in the urinary excretion of tetrodotoxin (TTX). These results indicate that TTX equally and reversibly affects myelinated nerve fibers throughout the entire length of the axon by lowering the conductance of sodium currents at nodes of Ranvier.

Retention of carbon dioxide in tissue following carbonic anhydrase inhibition in dogs.

To evaluate the retention of carbon dioxide in tissue during the reduction of carbonic anhydrase activity following the administration of 5, 10, 20, or 30 mg/kg of acetazolamide in dogs, we measured carbon dioxide pressure (PCO2) in arterial blood, mixed venous blood, alveoli, and tissue. Respiration was maintained at a constant level. In the control (noninjected) group, PCO2 in tissue did not change for 3 hours under controlled respiration. Following the injection of 5 to 30 mg/kg of acetazolamide, PCO2 increased in arterial blood, mixed venous blood, and tissue in a dose-related manner, and decreased in the alveoli. The (a-et)PCO2 widened to 21.9 +/- 1.0 mmHg from 0.6 +/- 1.0 mmHg, and the (t-v)PCO2 to 16.1 +/- 2.0 mmHg from 5.1 +/- 0.6 mmHg, in response to acetazolamide. It is suggested that carbon dioxide is retained in tissue when carbonic anhydrase activity is inhibited by acetazolamide.

Prevention by ulinastatin of decreased carbonic anhydrase activity induced by PMN elastase in vitro.

Disturbed carbon dioxide (CO2) elimination in adult respiratory distress syndrome (ARDS) has been considered to result from the dead space created by microthrombosis and vasoconstriction. However, another disturbance factor in CO2 elimination has been reported; the chemical dead space resulting from the inhibition of carbonic anhydrase (CA). This experiment was conducted to quantify the inhibition of CA activity by polymorphonucleocyte (PMN) elastase, which increases in ARDS. Different flasks containing solutions of CA, buffer, elastase, ulinastatin (an elastase antagonist), CA with PMN elastase, and CA with both PMN elastase and ulinastatin were prepared. Each flask was injected with sodium bicarbonate labeled with radioactive carbon (14C) and was shaken for 20 minutes; CA activity in each flask was measured by calculating the decrease in the coefficient (K) of 14C. It was observed that CA activity was inhibited dose-dependently by PMN elastase and that the inhibited activity was recovered by ulinastatin, which can inhibit PMN elastase. These findings indicate that CA activity in vitro could be inhibited by PMN elastase, which increases in ARDS, and suggests that disturbance of CO2 elimination could be reduced by using ulinastatin. It was concluded that ulinastatin could prevent the CA activity induced by PMN elastase in vitro.

Localization of efferent neurons innervating the pharyngeal constrictor muscles and the cervical esophagus muscle in the cat by means of the horseradish peroxidase method.

Following horseradish peroxidase (HRP) injection into the cephalopharyngeal muscle (CeP), the hyopharyngeal muscle (HP), the thyropharyngeal muscle (TP), the cricopharyngeal muscle (CP) and the cervical esophagus muscle (CE) of the cat, labeled neurons were identified in the nucleus retrofacialis and the rostral part of the nucleus ambiguus ipsilaterally. The rostral end of the labeled cell column was located more rostrally for CeP and HP than for TP, CP and CE. No difference was noted within the former two or within the latter three. The level of the caudal end of the labeled cell column became more caudal in the order of CeP, HP, TP and CP. The caudal end was located more rostral for CE than for TP. The neurons for CE were located more ventro-laterally than those for the other muscles.

Sympathetic innervation of the young canine heart using antero- and retrograde axonal tracer methods.

The present study was performed to determine the origin of cardiac sympathetic postganglionic fibers and to demonstrate their distribution in the heart. Young dogs were used in this study. Wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into various regions of the heart, and cholera toxin B subunit (CTB) and WGA-HRP were injected into the middle cervical ganglion or the stellate ganglion. In our retrograde axonal transport study, a large number of WGA-HRP-labeled cells were observed in the middle cervical and stellate ganglia bilaterally. Only a small number of the labeled cells were observed in the superior cervical ganglia bilaterally. In the anterograde axonal transport study, CTB and WGA-HRP labels showed terminal-like structures in the intrinsic ganglia located in the sinoatrial node, left atrium, and the origin of the ascending aorta. The labeled fibers were also observed around the coronary arteries.

MR imaging of idiopathic trigeminal neuralgia: correlation with non-surgical therapy.

Magnetic resonance (MR) findings in patients with idiopathic trigeminal neuralgia were evaluated and correlated with the effectiveness of non-surgical treatments. Thirty-four patients with idiopathic trigeminal neuralgia (ITN) were examined using T1- and T2-weighted spin-echo (SE) pulse sequence techniques to evaluate their trigeminal root-entry zones and the vessels contacted prior to non-surgical treatment (retrogasserian glycerol injection, peripheral nerve block, or only oral analgesics). Vascular contact at the proximal portion of the preganglionic segment (PGS) of the trigeminal nerve and deformity of the PGS on the affected side were observed in 97% and 47% of the patients, respectively. Non-surgical treatments were curative in 12 (67%) but failed in two (11%) of the 18 patients without deformed PGS. However, among 16 patients with deformed PGS, they were curative in only six (37.5%) and failed in four (25%). Results of this study suggest that MR imaging could be useful in the clinical assessment of trigeminal neuralgia prior to instituting non-surgical treatment.

[Sympathetic postganglionic innervation of external carotid artery, internal carotid artery, common carotid artery and aorta in the dog--experimental study using HRP and WGA-HRP].

The sympathetic postganglionic innervation of the external carotid artery, internal carotid artery, common carotid artery (CCA) and aorta was studied by using retrograde axonal transport of the horseradish peroxidase (HRP) and wheat germ agglutinin-HRP conjugates (WGA-HRP). When the powder of HRP was applied to the sheaths of internal and external carotid arteries, labeled cells were found only in the ipsilateral superior cervical ganglion (SCG). After injection of WGA-HRP into the walls of the (1) distal, (2) middle, and (3) proximal parts of the CCA, labeled cells were observed in the following ganglia, respectively; (1) the SCG and middle cervical ganglion (MCG), (2) the SCG, MCG and stellate ganglion (SG), and (3) the MCG and SG. These labeled cells were seen in these ganglia of both sides, but they were more marked ipsilaterally. Following injections of WGA-HRP into the walls of ascending and descending aortae, labeled cells were found in the bilateral MCG and SG. These results suggest that the vasodilation of the head and neck after stellate ganglion block using local anesthetic agents is caused by neuronal block of preganglionic sympathetic fibers passing through the stellate ganglion and terminating in the superior cervical ganglion.

[An experimental study of sensory innervation of the ureter in the dog using wheat germ agglutinin-horseradish peroxidase conjugates].

The sensory innervations of the ureter in the dog were studied using the anterograde and retrograde axonal transport of wheat germ agglutinin-horseradish peroxidase conjugates (WGA-HRP). Following upper ureteral injections, labeled cells were observed in the ipsilateral T7-L3 spinal ganglia to the injection site, with the greatest concentration at the T12-L2 levels. And labeled cells were seen in the contralateral T7--L3 spinal ganglia to the injection site with the greatest concentration at the T10 and L3 ganglia. Lower ureter injections resulted in the labeling of ipsilateral T11-Co1 and contralateral T9-Co1 spinal ganglia, with highest concentration at the ipsilateral L3 and S2 levels. Following thoracic and lumbar spinal ganglia T12, L1-L3 injections labeled fibers bundles were observed in the adventitia of the upper and lower ureter. Some labeled fibers were bifurcated from these bundles and passed through the two layers of the smooth muscles. In tunica submucosa and tunica propria mucosae, many labeled fibers were observed. A few labeled fibers were seen in the epithelium. After injections into the sacral and coccygeal spinal ganglia S1-Co1, labeled fibers were not observed in the upper ureter. Course and distribution of labeled fibers in the lower ureter were similar to those of the case in which injection was done into the thoracic and lumbar spinal ganglia.

[Perioperative administration of bicarbonated solution to a patient with mitochondrial encephalomyopathy].

A 16-year-old man with mitochondrial encephalomyopathy underwent biopsy and nephrectomy under general anesthesia. Mitochondrial encephalomyopathy is caused by mitochondrial dysfunction, and frequently accompanies elevation of lactic and pyruvic acid levels in the blood. It has been considered that problems of anesthesia for the patient with mitochondrial encephalomyopathy are the probability of hyperlactacidemia, the relevance to malignant hyperthermia, the possibility of myocardial disease and dysfunction of heart conduction system, respiratory depression due to muscle weakness, and so on. Therefore, to prevent hyperlactacidemia, we prepared the extracellular fluid solution including bicarbonic acid but no lactic and acetic acid, and infused the solution to the patient during anesthesia. By use of this solution, his lactic acid level was kept within the normal range during anesthesia and no metabolic acidosis occurred. His hemodynamics was stable and he showed normal response to vecuronium, recovering from anesthesia smoothly and postoperative course was uneventful.

[Reevaluation of spinal anesthesia in elderly people--an evaluation of circulatory changes].

Appropriate methods of anesthesia for the elderly people are being discussed as the ratio of elderly people in our society increases. During spinal anesthesia, hypotension was frequently observed in patients with hypertension, arteriosclerosis, coronary deficiency, and so on. It is also difficult to pass the needle between degenerated vertebrae. However, general inhaled anesthesia accompanies the respiratory complications and consciousness derangement after surgical operations more frequently than after spinal anesthesia. In this study, circulatory conditions during spinal anesthesia in elderly people (30-91 years old) were analyzed in 109 cases of spinal anesthesia. Hypotension occurred about 10 minutes and 40-60 minutes after injection of anesthetics and was frequent in patients of high aged group, but tachycardia was not observed among them. In addition, their blood pressure in the recovery room could not recover to the level before anesthesia. It is thought that hypotension during spinal anesthesia was induced by the vascular dilatation caused by sympathetic nerve block and the deficiency of reflective venous constriction in upper extremities and abdominal organs. Tachycardia may also produce hypotension. However, the reflexive vasoconstriction and tachycardia are thought to be poor on account of arteriosclerosis and down regulation of beta-receptor in elderly people. Therefore, during spinal anesthesia in the elderly people, the catecholamine released by the surgical stimulation could not increase blood pressure effectively. To prevent hypotension during spinal anesthesia in elderly people, it is advisable to employ the treatment for upregulation of beta-receptor before anesthesia and the administration of alpha . beta-receptor, epinephrine and dopamine for control of blood pressure during spinal anesthesia.

Diffusion of alcohol upon application of neuroadenolysis of the pituitary gland (NALP). An experimental study using HRP and WGA-HRP in the cat.

Diffusion of alcohol in neuroadenolysis of pituitary gland (NALP) was observed by injection of horseradish peroxidase (HRP) or wheat germ agglutinin-HRP conjugates (WGA-HRP) into the pituitary of the cat. After small-amount injection of WGA-HRP into the pituitary, WGA-HRP labeling was observed markedly around the third ventricle and the ventral part of the hypothalamus. While, in large-amount injection of WGA-HRP, it extended to all of the ventricular systems and dipped into the substances of the brain and spinal cord through the ependyma. These results suggest that the main site of action for alcohol injected into the pituitary is probably the hypothalamus.

[A case of obstructive ileus following the upper Gi barium swallow study with condensed barium due to severe constipation].

A 64-year-old woman visited my clinic with complaints of abdominal distension, constipation, and nausea. Since abdominal X-ray showed severe obstructive ileus following the upper GI barium swallow study, the patient was sent immediately to Saga Medical School Hospital for the emergency operation. As the result of the left hemicolectomy, two obstructive lesions were found at the sigmoid colon and the transverse colon. Nowadays, as the population of aged people increases and Japanese diet changes, colon cancers are increasing more rapidly. Since the half of colon cancers doesn't have any clinical symptoms of obstruction, the upper GI barium swallow study with condensed barium might lead a patient to some type of dangerous situation.

Three-dimensional analysis of the intrinsic cardiac ganglia in a young dog.

The intrinsic ganglia of the heart of a young dog were studied by computer graphic reconstruction to determine the accurate location. The heart was embedded in celloidin, and transverse sections were cut. Using every third 60 microns section, a series of 49 sections was mapped. Three-dimensional (3D) images were constructed by a personal computer. Numerous intrinsic ganglia, most of which were located in the epicardiun, were observed. The intrinsic ganglia were found in the base of the aorta and pulmonary vessels and from the base of the superior vena cava to the right atrium, i.e., the sinoatrial nodal region. Using the 3D reconstruction technique, the locations of the intrinsic ganglia could be accurately identified. Furthermore, it was demonstrated that these ganglia formed several groups which formed a continuity. This study suggested that it was necessary to consider the existence of the numerous intrinsic ganglia, when we studied the cardiac innervation.