Coexistence of fibrotic and chondrogenic process in the capsule of idiopathic frozen shoulders.

OBJECTIVE: To analyze changes in the capsule from idiopathic frozen shoulders and clarify their etiology. MATERIALS AND METHODS: Samples (the rotator interval capsule, middle glenohumeral ligament (MGHL), and inferior glenohumeral ligament (IGHL)) were collected from 12 idiopathic frozen shoulders with severe stiffness and 18 shoulders with rotator cuff tears as a control. The number of cells was counted and the tissue elasticity of the samples was calculated by scanning acoustic microscopy (SAM). The amount of glycosaminoglycan content was assessed by alcian blue staining. Gene and protein expressions related to fibrosis, inflammation, and chondrogenesis were analyzed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Furthermore, the total genes of the two groups were compared by DNA microarray analysis. RESULTS: The number of cells was significantly higher and the capsular tissue was significantly stiffer in idiopathic frozen shoulders compared with shoulders with rotator cuff tears. Staining intensity of alcian blue was significantly stronger in idiopathic frozen shoulders. Gene expressions related to fibrosis, inflammation, and chondrogenesis were significantly higher in idiopathic frozen shoulders compared with shoulders with rotator cuff tears assessed by both qPCR and DNA microarray analysis. CONCLUSION: In addition to fibrosis and inflammation, which used to be considered the main pathology of frozen shoulders, chondrogenesis is likely to have a critical role in pathogenesis of idiopathic frozen shoulders.

Elevated CO2 and nitrogen availability have interactive effects on canopy carbon gain in rice.

• Here we analysed the effects of CO2 (Ca ) elevation and nitrogen availability on canopy structure, leaf area index (LAI) and canopy photosynthesis of rice (Oryza sativa). • Rice was grown at ambient and elevated Ca (c. 200 µmol mol-1 above ambient, using the free-air CO2 enrichment, FACE) and at two N availabilities. We measured leaf area, area-based leaf N contents and leaf photosynthesis, and calculated net daily canopy photosynthesis. • FACE plants had higher light-saturated rates of photosynthesis (Pmax ) and apparent quantum yields than ambient plants, when measured at their own growth CO2 . Ca elevation reduced the total leaf N in the canopy (Nleaf ) but had no effect on LAI, and the average leaf N content (Nleaf /LAI) was therefore reduced by 8%. This reduction corresponded well with our model predictions. Leaf area index increased strongly with N availability, which was also consistent with our model. • Calculated canopy photosynthesis increased more strongly with Nleaf under elevated than under ambient Ca . This indicates that there is an N × Ca interactive effect on canopy carbon gain. This interaction was caused by the increase in LAI with N availability, which enhanced the positive effect of the higher quantum yield under Ca elevation.

Duodenogastric reflux following cholecystectomy in the dog: role of antroduodenal motor function.

BACKGROUND: Duodenogastric reflux has been implicated in the pathogenesis of gastric ulcer and gastritis. Duodenogastric reflux after cholecystectomy is also a possible cause of post-cholecystectomy syndrome. AIM: To investigate the role of antroduodenal motor function in increased duodenogastric reflux following cholecystectomy and the effect of trimebutine maleate (trimebutine) on the duodenogastric reflux in conscious dogs. METHODS: Antropyloric and duodenal motility and bile acids content in the gastric juice were measured for 3 h during the inter-digestive state in dogs with or without cholecystectomy. RESULTS: Bile acids content in the gastric juice of cholecystectomized dogs was significantly higher than that of non-cholecystectomized dogs. The frequency of pyloric relaxation during phase II of the migrating motor complex was significantly increased following cholecystectomy. Intravenous infusion of trimebutine inhibited both the increased duodenogastric reflux and the frequency of pyloric relaxation in the cholecystectomized dog. CONCLUSION: Duodenogastric reflux and frequency of pyloric relaxations were increased in cholecystectomized dogs and trimebutine suppressed both of them. These findings suggest that the increased frequency of pyloric relaxation contributes to the duodenogastric reflux following cholecystectomy.

The effect of nociceptin, an endogenous ligand for the ORL1 receptor, on rat colonic contraction and transit.

To assess the role of ORL1 (opioid receptor-like 1) receptor in the bowel movement, we investigated the effect of nociceptin on colonic contraction and transit in rats. Nociceptin (0.1-100 nM) concentration-dependently caused an immediate tonic contraction followed by rhythmic waves of contractions in the isolated colon. The response to nociceptin (10 nM) was not affected by the classical opioid receptor antagonists, naloxone, naltrindole and nor-binaltorphimine. Suppression of effect of inhibitory neurotransmitters using pituitary adenylate cyclase activating polypeptide(6-38) (PACAP-(6-38); 3 microM), vasoactive intestinal polypeptide(10-28) (VIP-(10-28); 3 microM) and N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 microM) did not influence the nociceptin-induced contractions. In anesthetized rats, intravenous administration of nociceptin (1 microg/kg) or morphine (1 mg/kg) caused phasic contractions in the proximal colon. Pretreatment with naloxone (300 microg/kg, i.v.) abolished the contractions induced by morphine, but not by nociceptin. The rate of large intestinal transit was dose-dependently accelerated by nociceptin (0.03-3 microg/kg, s.c.), but was retarded by morphine (1.7-5 mg/kg, s.c.). These results indicate that stimulation of ORL1 receptor accelerates the colonic contraction and transit independently from opioid receptors.

KF31327, a new potent and selective inhibitor of cyclic nucleotide phosphodiesterase 5.

The effects of KF31327 (3-ethyl-8-[2-(4-hydroxymethylpiperidino)benzylamino]-2,3-dihydro-1H-imidazo[4,5-g]quinazoline-2-thione dihydrochloride) on phosphodiesterase 5 (cyclic GMP-specific phosphodiesterase) activity and platelet aggregation were investigated and compared with those of sildenafil, a well-known phosphodiesterase 5 inhibitor. KF31327 inhibited phosphodiesterase 5 from canine trachea (K(i)=0.16 nM) more potently than sildenafil (K(i)=7.2 nM). The kinetic analysis revealed that KF31327 was a non-competitive inhibitor. In the presence of nitroglycerin (nitric oxide generator), both compounds inhibited the collagen-induced aggregation of rabbit platelets at less than 0.1 microM, augmenting intracellular cyclic GMP level without affecting cyclic AMP. In contrast, in the absence of nitroglycerin, a higher concentration (10 microM) of KF31327 was required to inhibit platelet aggregation and increased both cyclic nucleotide levels. However, 10 microM sildenafil did not affect aggregation despite elevation of cyclic GMP comparable to that in the presence of nitroglycerin. These results indicate that in the presence of nitroglycerin, the inhibition of platelet aggregation by KF31327 is due to the elevation of cyclic GMP, whereas the mechanism underlying the inhibition without nitroglycerin might be related to a rise in intracellular cyclic AMP.

[Effects of trimebutine on colonic propulsion in mice].

Effects of oral administration of trimebutine on colonic propulsion in conscious mice were studied by measuring the time required to evacuate a bead which had been inserted into the colon, and compared with those of metoclopramide and domperidone. In normal animals, trimebutine (10 and 50 mg/kg), metoclopramide (50 mg/kg) and domperidone (50 mg/kg) had no effect on the bead evacuation. Metoclopramide and domperidone at 30 mg/kg showed no effect on the delay of colonic propulsion induced by clonidine, while trimebutine (10 and 30 mg/kg) restored the delay significantly. Trimebutine also showed restoration of the delay induced by loperamide. On the acceleration of the propulsion induced by neostigmine, trimebutine (10 and 30 mg/kg) showed an inhibition. In addition, trimebutine (3-30 mg/kg) dose-dependently suppressed the development of soft feces and/or diarrhea induced by neostigmine. According to the results, it is concluded that trimebutine produces both acceleration and inhibition on the colonic propulsion in mice.

Comparison of the effects of T-1815, yohimbine and naloxone on mouse colonic propulsion.

The colonic prokinetic activity of a newly synthesized compound, T-1815, administered orally, was compared with that of yohimbine and naloxone in mice. The time required to evacuate a glass bead inserted into the distal colon was taken as an index of prokinetic activity. Clonidine (3-30 micrograms/kg s.c.), and loperamide (0.3-3.0 mg/kg s.c.) delayed bead expulsion in a dose-dependent manner. Yohimbine (0.3-10 mg/kg) and T-1815 (0.1-10 mg/kg) showed a dose-dependent reduction of the delay in evacuation induced by clonidine, but naloxone had no effect. The loperamide-induced retardation of colonic propulsion was reduced by naloxone (0.3-10 mg/kg) and T-1815 (0.1-10 mg/kg) in a dose-dependent manner, but yohimbine had no effect. In normal animals, yohimbine and naloxone had no significant effect on evacuation, while a slight acceleration was observed with T-1815 at 10 mg/kg. No soft feces and/or diarrhea were observed with any of the three test drugs. These results indicate that T-1815 appears to be a unique colonic prokinetic compound, the action of which may be mediated through mechanisms other than antagonism for alpha 2-adrenoceptors or opioid receptors.

Effect of a new colonic prokinetic compound, T-1815, on gastrointestinal motility in anesthetized and conscious fasted dogs.

Effect of T-1815, a new colonic prokinetic compound, on gastrointestinal motility was studied in anesthetized and conscious dogs fasted for 24 hr before experiment. In anesthetized dogs, intravenous injection of T-1815 in doses of 0.3-3.0 mg/kg caused a biphasic effect on the gastric motility, a slight decrease followed by a slight increase. While the compound elicited only an increase in motility of the duodenum, jejunum and colon. In the colon, high-amplitude contractions were observed in 2 out of 5 animals at 1 mg/kg, i.v. of T-1815 and 4 out of 5 animals at 3 mg/kg. Bethanechol at 0.01 mg/kg, i.v. produced only a potentiation of the motility in all of the sites, but never induced high-amplitude contractions in the colon. During the interdigestive state in conscious dogs, intravenous T-1815 at 1 and 3 mg/kg caused contractions similar to the interdigestive phase III contractions at the stomach and duodenum in only 2 out of 7 experiments, and colonic motility was slightly depressed at 3 mg/kg. Oral administration of T-1815 at 30 and 50 mg/kg did not elicit the phase III-like contractions but produced persistent contractions at the stomach and duodenum in 2 out of 4 conscious animals during the interdigestive state. In the proximal and middle colon, high-amplitude contractions were observed in 5 out of 7 animals by 10-50 mg/kg, p.o. of T-1815. From the above results, it is concluded that the pharmacological effect of T-1815 on gastrointestinal motility is different from that of the cholinergic agonist. In addition, T-1815 seems to have a characteristic to induce high-amplitude contractions which are known to be closely related to defecation.

Clinical evaluation of amoxycillin in the treatment of syphilis.

Following demonstration of in vitro activity of amoxycillin against Treponema pallidum, a clinical research group was set up to study the effects of amoxycillin against various stages of syphilitic infection in men. A total of eighty-nine cases, fifteen primary, twenty-nine secondary, thirty late and fifteen adult congenital patients have been investigated. One hundred per cent effectiveness was recorded for primary and secondary syphilis; 66.7% for late syphilis and 60% success for adult congenital syphilis. In 10.4% of cases there was a transient elevation of SGOT and SGPT although it is not certain whether this was a reaction to the drug itself. There were three incidences of drug-related rash and two other minor side-effects. Amoxycillin is thus a safe and effective oral agent for the treatment of all stages of syphilis in man.

[Therapeutic effect of oral doxycycline on syphilis (author's transl].

Eighty-one patients with syphilis were treated with oral doxycycline. A course of the antibiotic treatment consisted of 200 mg of doxycycline daily in two divided doses for 28 days. The course was repeated three to four times a year with an interval of several months. Quantitative Venereal Disease Research Laboratory (VDRL), Wassermann reaction (WR), and Treponema pallidum hemagglutination assay (TPHA) tests were performed monthly to evaluate the therapeutic effect of doxycycline treatment. The response rate was 100% for primary, 91.7% for early, 63.0% for late, and 61.8% for congenital syphilis in adults. No notable side effects were encountered except for epigastric fullness in four patients, which did not require the treatment to be discontinued. No abnormalities were detected in the results of laboratory tests.

[Laboratory and clinical studies of cefmetazole in serious infection by Staphylococcus (author's transl)].

Cefmetazole (CMZ) is an antibiotic agent belonging to the cephamycin group, which is resistant to beta-lactamase and has a broad antibacterial spectrum covering from Gram-negative to -positive organisms. Although this agent has been proved to have an antibacterial activity against Staphylococcus spp., it has not been used for treatment of the infections caused by the organism. Thus, 62 strains of S. aureus isolated clinically were compared for their sensitivity to CMZ, cefoxitin (CFX), cefuroxime (CXM), cefazolin (CEZ), and ampicillin (ABPC). In addition, 5 children suffering from septicemia due to S. aureus were treated with CMZ 158 mg/kg at a mean daily dose for a mean period of 14 days. The dose was used after dividing into 3 and 4 equal parts in 1 and 4 children, respectively. One old patient with septicemia was given 2,000 mg of CMZ twice daily for 4 days and once daily for subsequent 3 days. Another child with bacterial meningitis was treated with 50 mg/kg of CMZ 4 times daily for 63 days. The drug was given intravenous injection by one-shot or drip infusion in all cases under observation of clinical effects, bacteriological effects and side effects. The MIC of CMZ against S. aureus at inoculum sizes of 10(6) and 10(8) cells/ml was 1.56 mcg/ml in 72.6 and 56.5% of the strains, respectively. When 5 drugs were compared on the basis of the MIC to which the largest number of strains were sensitive, CEZ was most active, and CMZ was ranked in the next place and similar to CXM in activity. However, when the whole range of the MIC was considered, CMZ was more excellent than CXM, its MIC was lower than those of CEZ, CFX and ABPC in a greater number of strains. It was considered from the results that the serum level of CMZ was effective against 100 and 93.5% of strains at an inoculum size of 10(6) cells/ml and against 100 and 83.9% of strains at an inoculum size of 10(8) cells/ml until 4 and 6 hours after a one-shot intravenous injection of 50 mg/kg of Moni-trol I standard, respectively in the children. Thus, CMZ is expected to manifest a sufficient effect on septicemia caused by S. aureus in children who receive a one-shot intravenous injection of 50 mg/kg of it 4 times daily. Treatment with CMZ was clinically evaluated to be excellent in 3, good in 3 and poor in none of 6 patients with septicemia due to S. aureus, and fair in the 1 with Staphylococcal meningitis. The bacteriological result was excellent, since the causal organisms were eradicated in all cases. With regard to side effects, abnormal eosinophilia was found in 2 cases, but it was no ascribable to this drug in 1 of them. GOT showed an abnormal rise in 1 case and both GOT and GPT in 1, although they were considered not to be related to this drug in either case. It is considered from these results that CMZ is a valuable drug in treatment of septicemia due to S. aureus.

[Usefulness of pharmacokinetic modulating chemotherapy (PMC) for the postoperative adjuvant therapy of colorectal carcinoma: a preliminary report].

Pharmacokinetic modulating chemotherapy (PMC) using oral UFT and continuous venous 5-FU infusion was administered to 22 resectable patients with Dukes' B2-D colorectal carcinomas. The regimen was arranged as follows: Group A (n = 12) UFT 300-450 mg/day, 5 days a week and 5-FU 440-600 mg/m2/24 hr (750-1,000 mg/body/24 hr) once a week, Group B (n = 10), UFT less than 300 mg/day, 5 days a week, and/ or 5-FU less than 440 mg/m2/24 hr (750 mg/body/ 24 hr) once a week. The control group (Group C, n = 26) was selected at random from among non-PMC cases matched for other background factors and in which surgery had been performed during the past 4 years. Fifteen out of 26 patients in Group C were treated with 5-FU masked compounds orally. The cumulative 2 year recurrent rates of Groups A, B and C were 8.3%, 52.0% and 50.0%, respectively; the rate of Group A was significantly lower than that of Group B (p < 0.05). Four patients who suffered from PMC-related side effects of grade 1-2 wanted to decrease their dosage of UFT and/or 5-FU. They were registered in Group B. These results suggest that the regimen of Group A was advantageous in improving the prognosis after resection of Dukes' B2-D colorectal carcinoma.

A study of the internal structure of the Japanese mandible.

The thickness of the substantia compacta and the volume and width of the trabecular bone of the substantia spongiosa were investigated by soft X-ray photographs made of thin sections of many kinds of dentulous and edentulous mandibles. The results were: 1) The thickness of substantia compacta is especially thick on the lingual side in the incisor region and thickest in the molar region in all materials. At the base of mandible, the thickness is essentially the same in all regions, but, the thickness of dentulous materials is greater than of edentulous ones. 2) On the upper part, the volume of trabecular bone is less in the premolar region in both edentulous and dentulous material than in other regions, however, there is relative more in edentulous than in dentulous. In the central part, there is almost the same amount of trabecular bone in the dentulous and edentulous material. 3) The width of the trabecular bone in the substantia spongiosa is greater in the incisor region than in other regions in all materials. In the upper and central part, it is smaller in the premolar region in both edentulous and dentulous material but, it increases in the molar region in the edentulous materials.

Quantitative and morphological studies of the trabecular bones in the condyloid processes of the Japanese mandibles; changes due to aging.

The structure of bone changes with advancing age. In order to observe changes in the trabecular bone structure of the mandibular condyloid process and their relationship to age, the mandibular condyloid process and third lumbar vertebra were extracted from cadavers from several age groups, and changes in trabecular bone structure due to age were compared. Comparison of the trabecular bones of the lumbar vertebra and condyloid processes from single cadavers by age revealed a clear reduction in trabecular bone density and width in the lumbar vertebra accompanying advancing age. In the condyloid process in contrast no major changes were observed; it appears that the effects of aging are slight.

A study of the internal structure of the mandibular ramus in Japanese.

To clarify the internal structure of the mandibular ramus in Japanese adults, we performed bone morphometry. Specimens were obtained from four areas: the mid-area between the mandibular foramen and the lowest point of the mandibular notch, areas immediately above and below the mandibular foramen, and the mid-area between the mandibular foramen and the mandibular angle. The mandibular ramus was divided into the anterior and posterior parts, and morphometric analysis was performed on the four areas in each part. The percentage of the trabecular bone area in spongy bone was higher in the anterior part than in the posterior part. In both the anterior and posterior parts, the percentage of trabecular bone was the highest in the most inferior area. Trabecular bone was thicker in the anterior part than in the posterior part. Both in the anterior and posterior parts, trabecular bone was the thickest in the most inferior area. The arrangement of trabecular bone was more complicated in the anterior part than in the posterior part. Trabecular bone was most frequently arranged in the anteroposterior direction. In the superior area of the posterior part, much trabecular bone ran from the posterior buccal side toward the anterior lingual side. Compact bone was thicker in the anterior part than in the posterior part and on the buccal side than on the lingual side. No age-related changes were observed in any element of trabecular bone structure.