The effect of interleukin-1 on iron metabolism in rats

The effect of interleukin-1 on iron metabolism in rats was evaluated. Plasma iron decreased from 184 +/- 16 micrograms/dl (mean +/- SE) to 24 +/- 12 at 6 hours after interleukin-1 intramuscular administration in non-fasting rats and 109 +/- 6 micrograms/dl to 12 +/- 1 micrograms/dl in fasting rats, which was significantly lower than in control rats. Ferrokinetic studies showed a more rapid disappearance rate and lower iron turnover in interleukin-1-injected rats. The release of iron from the mononuclear phagocyte system to plasma was studied at 3 h after interleukin-1 administration. Although the percent of radioactivity in plasma of the total injected dose was 3.2 +/- 0.6% in interleukin-1, which was significantly lower than in the control rats (5.4 +/- 0.6%) at 9 h after intravenous injection of 59Fe chondroitin ferrous sulfate, there was no difference between the amount of 59Fe released from the mononuclear phagocyte system over the first 9 h in interleukin-1 and control rats. These data appear to imply that iron release is unimpaired but that, for some reason, there is an enhanced rate of clearance of the 59Fe once it has been released from the mononuclear phagocyte system into the plasma.     

Epithelium-dependent and -independent inhibitory effects of sivelestat, a neutrophil elastase inhibitor, on substance P-induced contraction of airway smooth muscle in lipopolysaccharide-treated guinea-pigs.

The underlying mechanism involved in the interaction between neutrophil elastase inhibitors and tachykinins has not been elucidated. In this study we have examined the effects of sivelestat, a neutrophil elastase inhibitor, on the in vitro responses of airways from lipopolysaccharide (LPS)-untreated or -treated guinea-pigs to substance P. Substance P (0.01-30 micromol/l) produced concentration-dependent contractions of both tracheal and bronchial ring preparations of LPS-untreated or -treated guinea-pigs. Responsiveness to substance P in these isolated airway preparations was augmented by either epithelium removal or LPS treatment. In epithelium-intact tracheal ring preparations isolated from LPS-untreated guinea-pigs, sivelestat (100 micromol/l) significantly inhibited substance P-induced contractions. The inhibitory action was markedly attenuated by pretreatment with L-NAME (100 micromol/l) or indomethacin (2 micromol/l), and was almost undetected following removal of the epithelium. On the other hand, in bronchial ring preparations isolated from LPS-untreated guinea-pigs, sivelestat had only a very slight effect on substance P-induced contraction of the epithelium-intact preparation, whereas sivelestat greatly inhibited contraction in epithelium-removed bronchial ring preparations. In LPS-treated guinea-pigs, whether the epithelium was intact or not, sivelestat significantly inhibited the substance P-induced contraction of bronchial ring preparations. Pretreatment with L-NAME (100 micromol/l) or indomethacin (2 micromol/l) did not affect the inhibitory effect of sivelestat in bronchial ring preparations. In conclusion, epithelium removal or LPS treatment induced hyperreactivity to substance P in the guinea-pig airway. Sivelestat caused epithelium-, nitric oxide- and prostaglandin-dependent inhibition of the substance P-induced contraction of isolated guinea-pig tracheal ring preparations. In contrast, the inhibitory effect of sivelestat on substance P-induced contraction of guinea-pig bronchial ring preparations is mediated by epithelium-, nitric oxide- and prostaglandin-independent mechanisms. Sivelestat may be effective in reducing the airway hyperresponsiveness to tachykinins induced by epithelial injury as occurs in LPS-mediated inflammatory lung diseases.     

Multiple sclerosis with higher cerebral dysfunction: a case report

Higher cerebral dysfunctions such as aphasia, apraxia and agnosia have seldom been reported in multiple sclerosis (MS). 12 year-old right-handed boy felt unsteadiness of the body and headache for several days. Two months later, he had the same episode and complained of visual disturbance, and weakness and sensory disturbance on the face and the extremities. Additionally, he showed amnestic aphasia, acalculia, ideomotor apraxia, finger agnosia and right-left disorientation. Cerebrospinal fluid examinations revealed increases IgG, myelin basic protein and neuron specific enolase (11%, 25 ng/ml and 28.8 ng/ml, respectively). X-ray CT scan and MRI-CT examinations revealed sclerotic lesions on the left parietal white matter and the right mid-brain. The diagnosis was made as MS. He was treated with m-PSL (methyl-prednisolone) pulse therapy for three weeks and consecutively treated with PSL for four weeks. He recovered gradually, but visual disturbance and facial palsy remained. After seven months MRI-CT showed a high signal intensity on the left parietal white matter in spite of the disappearance of the lesion on X-ray CT scan. We suggest that these higher cerebral dysfunctions may result from the lesion of the left parietal white matter which produces a disconnection between each cortical area.     

Iron deficiency down-regulates the Akt/TSC1-TSC2/mammalian Target of Rapamycin signaling pathway in rats and in COS-1 cells

Iron deficiency (ID) is one of the most commonly known forms of nutritional deficiencies. Low body iron is thought to induce neurologic defects but may also play a protective role against cancer development by cell growth arrest. Thus, ID may affect cellular pathways controlling cell growth and proliferation, the mechanism of which is still not fully understood. The serine/threonine protein kinase Akt and its downstream target, the mammalian Target of Rapamycin (mTOR), is known to play a crucial role in the regulation of cell growth and survival. Therefore, we hypothesized that Akt/mTOR pathway could be influenced by ID. Three-week-old male Wistar-strain rats were divided into 3 groups and the 2 groups had free access to a control diet (C group) or an iron-deficient diet (D group). The third group (PF group) were pair-fed the control diet to the mean intake of the D group. After 4 weeks, rats were killed and their brains were sampled. In separate experiments, COS-1 cells were cultured with or without the iron chelator deferoxamine. Western blots of brain samples and COS-1 lysates were used to analyze the expression and phosphorylation state of Akt, TSC2, mTOR, and S6 kinase proteins implicated in the Akt/mTOR pathway. Using 2 different ID models, we show for the first time that iron deficiency depresses Akt activity in rats and in COS-1 cells, leading to a decrease in mTOR activity.     

Fluctuating PEEP (F–PEEP) versus conventional PEEP in dogs with asymmetrical lung injury

Fluctuating PEEP (F-PEEP) is a newly developed PEEP in which end-expiratory pressure (EEP) is periodically changed within a certain range. In a dog model with unilateral lung injury induced by the introduction of hydrochloric acid, F-PEEP in which the EEP was periodically changed from 0.5 to 1.5 kPa at periods of 6 min, and conventional PEEP (C-PEEP) with an optimized EEP of 1.0 kPa, were each applied for 30 min. F-PEEP produced a significantly greater improvement of PaO2 and intrapulmonary shunt (QS/QT) than C-PEEP, and at the low EEP phase, the greatest improvement accompanied by an increased dynamic compliance and a large cardiac output was obtained. These results suggest that F-PEEP provides a useful mode of artificial ventilation for the treatment of unilateral lung injury.     

Effect of ceruletide on microvibration in schizophrenics

Ceruletide, a potent analogue of cholecystokinin, was administered by injection to eight schizophrenics treated with neuroleptics. We examined the dose–response effect on microvibration (MV) recorded from the chin of these patients. After 15 min of bed rest, MV was recorded for 5 min as a control recording. Subsequently, saline or ceruletide, at a dose of either 0.4 m?g/kg or at 0.8 m?g/kg, was injected according to a Latin square design with an interval of 4 weeks for washing out the drug effect and MV was recorded for 30 min. MV data obtained were subjected to the fast Fourier transform and an average power spectrum was computed. A three-way analysis of variance for these data was performed upon dose-effect, time-effect after treatment, and band-effect of the average power spectrum. The present results were similar to previous findings which had revealed effects of ceruletide on tardive dyskinesia symptoms, namely, the effects of ceruletide on MV were different according to the subjects (three cases: facilitation followed by inhibition, three cases: inhibition, two cases: no effects). The dose-response curve of ceruletide appears to be linear in some cases and an inverted U-shape in other cases. Present findings showed small doses of systemically administered ceruletide would modify muscle tonus of schizophrenics under chronic treatment of neuroleptics, and provided further reason for the therapeutic drug of tardive dyskinesia.     

Hypoosmotic swelling test of sperm

For the diagnosis and evaluation of the therapy for male infertility and for predicting the outcome of AIH and IVF-ET, technically simple, replicable tests that can be performed virtually anywhere and that have definite reliability are required. The results of the HOS test correlate well with the functions of the sperm cell membrane, indicating such aspects as motility, and it is thought to be a particularly effective test of human sperm fertility. Because the HOS test reflects the functions and integrity of the sperm cell membrane, it should be possible to use it to predict the potential for fertilization of frozen sperm.     

Availability of 4'galactosyllactose (O-beta-D-galactopyranosyl-(1----4)-O-beta-D-galactopyranosyl-(1----4)- D-glucopyranose) in rat

O-beta-D-Galactopyranosyl-(1----4)-O-beta-D-galactopyranosyl-(1----4)-D- glucopyranose (designated as 4'GL) is produced from lactose by Cryptococcus laurentii. The influence of chronic ingestion of 4'GL on body weight gain, organ weight, serum lipids, and liver lipids was investigated in rats. The body weight gains of the 5% and 10% 4'GL-diet groups were higher than that of the control group. Food intake and fecal dry weight were significantly increased (p less than 0.05) by 4'GL feeding. The 4'GL diet produced a significant increase (p less than 0.01) in the wet weight and contents of both the cecum and the colon. However, no significant increase was observed in the weight of the stomach, small intestine, liver, or other organs. The effects of 4'GL on serum and liver lipid levels were not observed in this experiment. The digestion of 4'GL was measured in vitro using the artificial gastric juice, alpha-amylase of human saliva, alpha-amylase of hog pancreas, and mucosa of rat intestine. 4'GL was not hydrolyzed by these enzymes. Long-term ingestion of 4'GL did not cause any induction of 4'GL hydrolyzing enzyme activity in the rat small intestine.     

Ruptured congenital aneurysm of the sinus of valsalva in the aged

Ruptured aneurysm of the sinus of Valsalva is a rare cardiac lesion. A ruptured aneurysm of the sinus of Valsalva in the right ventricle of a 64-year-old man was successfully repaired. The patient was admitted to the hospital with high fever and chest oppression. Diagnosis was made by two dimensional echocardiography, cardiac catheterization, and cardiac angiography. An aortotomy, main pulmonary arteriotomy, and right ventriculotomy were performed. There was no VSD, and the aneurysm originated from the right coronary sinus, rupturing into the right ventricle inlet portion. The ruptured aneurysm of the sinus of Valsalva was closed with a Dacron patch from inside the aorta. He is doing well after surgery. There was no heart murmur. CTR decreased and pulmonary blood flow fell to a normal value. As far as we know, this patient is the second oldest patient in Japan with surgical repair.     

A novel method to estimate the contribution of the vapor activity of essential oils in agar diffusion assay.

By the combined use of agar diffusion, agar vapor and agar vapor-inhibitory assays, contribution of the vapor activity of essential oils was quantitatively estimated. The test organisms were Trichophyton mentagrophytes and Aspergillus fumigatus. Agar vapor assay was used to confirm the vapor activity of the oils. The parameter delta defined as a contribution index of the vapor activity was calculated by (1 - b-c/a-c) x 100, where a is inhibitory diameter in the diffusion assay, b is inhibitory diameter in the vapor-inhibitory assay and c is diameter of the sealed ring in the vapor-inhibitory assay (21 mm). Many of the essential oils examined showed a delta value near 100, thus providing the major contribution of the vapor activity to the inhibitory diameter. Essential oils containing aldehyde as major constituent showed low delta value, indicating the major inhibition was due to agar diffusion. Major essential oil components behaved similarly; the delta value was increased in the following order: aldehyde < phenol < alcohol < ester, oxide, hydrocarbon, indicating the enhanced contribution of the vapor activity in that order.