Association between habitual hot spring bathing and depression in Japanese older adults: A retrospective study in Beppu.

OBJECTIVES: Thermal therapy is used to manage various psychological diseases, such as depression. We investigated the relationship between hot spring bathing and depression in older adults using questionnaire responses. DESIGN AND SETTING: We comprehensively evaluated the preventive effects of long-term hot spring bathing in 10429 adults aged ≥ 65 years in Beppu, Japan, by conducting a questionnaire study on the prevalence of depression (n = 219). MAIN OUTCOME MEASURES: Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a multivariable logistic regression model for history of depression. RESULTS: A separate multivariable logistic regression model for inference showed that female sex (OR, 1.56; 95 % CI, 1.17-2.08; p = 0.002), arrhythmia (OR, 1.73; 95 % CI, 1.18-2.52; p = 0.004), hyperlipidemia (OR, 1.63; 95 % CI, 1.14-2.32; p = 0.006), renal disease (OR, 2.26; 95 % CI, 1.36-3.75; p = 0.001), collagen disease (OR, 2.72; 95 % CI, 1.48-5.02; p = 0.001), allergy (OR, 1.97; 95 % CI, 1.27-3.04; p = 0.002), and habitual daily hot spring bathing (OR, 0.63; 95 % CI, 0.41-0.94; p = 0.027) were independently significantly associated with a history of depression. CONCLUSIONS: We found an inverse relationship between habitual daily hot spring bathing and history of depression. Prospective randomized controlled trials on habitual daily hot spring bathing as a treatment for depression are warranted to investigate whether the use of hot springs can provide relief to those with psychiatric and mental health disorders.

Effects of orthotic therapeutic electrical stimulation in the treatment of patients with paresis associated with acute cervical spinal cord injury: a randomized control trial.

STUDY DESIGN: A randomized controlled trial. OBJECTIVES: To determine the effects of orthotic therapeutic electrical stimulation (TES) on the hand in patients with paresis associated with acute cervical spinal cord injury. SETTING: Spinal Injuries Center, Fukuoka, Japan. METHODS: The study included patients treated for spinal cord injuries (Frankel classification, grades B and C) at our institution within 1 week post injury between May 2011 and December 2014. The patients were allocated randomly to TES and control groups at the time of admission and underwent TES+conventional training or conventional training alone, respectively. Both hands of each patient were treated in the same way. The primary outcome was total passive motion (TPM) of the fingers (degrees). The secondary outcomes were edema (cm) and the upper-extremity motor scores of the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI). After randomization, outcomes were assessed at 1 week, 1 month and 3 months post injury in both groups. RESULTS: Twenty-nine individuals were assessed at 3 months (15, TES; 14, control). There were no significant between-group differences for TPM of the fingers, edema and upper-extremity motor scores at 1 week, 1 month and 3 months after injury, although TPM of the fingers tended to be lower in the control group. CONCLUSIONS: It is unclear from the results of this study whether TES has a therapeutic effect on TPM, edema or the upper-extremity motor score of the ISNCSCI. The results of this study provide useful data for future meta-analyses.

Perforated appendicitis causing thigh emphysema: a case report.

We report a case of thigh emphysema resulting from perforated appendicitis. The patient was an 83-year-old man who had no apparent abdominal signs and was initially misdiagnosed as having psoas abscess. Magnetic resonance imaging of the pelvis revealed appendicitis, and a barium enema showed a leakage of enhanced contrast material from the appendix region down into the thigh. A retroperitoneal perforation of the retrocaecal appendix without peritonitis was diagnosed. The patient underwent an appendectomy and curettage of the retroperitoneal and psoas muscle spaces, as well as the thigh. He recovered gradually, though the abscess had extended into the hip joint and resulted in osteomyelitis, requiring an additional procedure of resection arthroplasty. The patient fully recovered with no signs of infection one year postoperatively.

Effects of biotin supplementation on serum biotin levels and physical properties of samples of solar horn of Holstein cows.

Effects of dietary biotin supplementation on serum biotin levels and physical properties of sole horn of 40 Holstein cows were evaluated. The mean serum biotin level in biotin-supplemented cows after 10 mo of biotin supplementation (1163.2 +/- 76.2 pg/mL) was significantly higher (P = 0.007) than that in control cows (382.0 +/- 76.2 pg/mL). The sole horn of biotin-supplemented cows was significantly harder (P = 0.026) and had a significantly lower moisture content (P = 0.021) than that of control cows. No morphologic differences in horn tubules or intertubular horn were found between the biotin-supplemented and control cows. The total lipid content of sole horn was significantly higher (P = 0.030) in the biotin-supplemented cows than in the control cows. These results suggest that dietary biotin supplementation causes increases in serum biotin levels and changes in physical properties and fat content of sole horn.

Retinal dysfunction in cancer-associated retinopathy is improved by Ca(2+) antagonist administration and dark adaptation.

PURPOSE: It was recently found that recoverin acts as an autoantigen recognized by sera of patients with cancer-associated retinopathy (CAR), and that CAR-like retinal dysfunction is produced by intravitreous administration of anti-recoverin antibody in Lewis rat eyes. To examine the pathologic molecular mechanism of CAR, and to elucidate an effective therapy for CAR, the function and morphology of CAR were compared with those of phototoxic retinal damage, another form of photoreceptor dysfunction, and the effect of nilvadipine, a Ca(2+) antagonist, on the retinal degenerations was studied, using these models. METHODS: Under different illumination conditions and/or medication with nilvadipine, the functional and morphologic properties of the retinas were evaluated after intravitreous injection of anti-recoverin antibody into Lewis rat eyes (six rats, 12 eyes in each experimental condition), using electroretinogram (ERG), rhodopsin phosphorylation, and light microscopy. RESULTS: Anti-recoverin antibody administered into the vitreous of Lewis rat eyes induced a significant decrease and increase of ERG responses and rhodopsin phosphorylation levels, respectively, under cyclic or continuous light. Similar changes were observed in eyes of rats bred under continuous illumination that did not receive anti-recoverin antibodies. However, anti-recoverin antibody-induced retinal dysfunctions were not observed in rat eyes under dark conditions. Administration of nilvadipine, a Ca(2+) antagonist, to the anti-recoverin antibody-treated rats and rats with phototoxic retinal dysfunction caused significant improvement of the deterioration of ERG and normalization of rhodopsin phosphorylation. CONCLUSIONS: The present data indicate that anti-recoverin antibody-induced retinal dysfunction was functionally similar to phototoxic retinal dysfunction and was markedly suppressed under dark conditions or by systemic administration of a Ca(2+) antagonist.

Development of a real-time hand dose monitor for personnel in interventional radiology.

Medical procedures denoted as interventional radiology require operation near an X ray beam, which brings high dose exposures to the operators' hands. For the effectual control of their extremity doses, a prototype of a real-time wrist dosemeter has been developed, hand dose monitor (HDM), based on a single silicon detector. Experiments were performed to test its response to diagnostic X rays. The HDM was highly sensitive and showed a linear response down to doses of a few tens of microsieverts. Though dose rate, energy and angular dependence of the response were observed in some extreme conditions, the HDM was proved to be of practical use if it was appropriately calibrated. Since an HDM enables personnel to check their hand doses on a real-time basis, it would enable medical staff to control the exposure themselves.

Role of interaction between two silkworm RecA homologs in homologous DNA pairing.

Recombinant BmRad51 and BmDmc1, silkworm homologs of the Escherichia coli RecA proteins catalyzing the homologous DNA pairing, were purified from E. coli cells carrying expression vectors. These possessed different enzymatic properties in the joint molecule formation between single-stranded circular DNA and homologous linear double-stranded DNA. The requirement of single-stranded circular DNA for the efficient reaction was twofold higher in BmRad51 than in BmDmc1. Although able to mediate the joint molecule formation independently, a complex of the two enzymes formed prior to single-stranded DNA binding was found to have augmented efficiency of the pairing reaction.

Aluminum-induced 1-->3-beta-D-glucan inhibits cell-to-cell trafficking of molecules through plasmodesmata. A new mechanism of aluminum toxicity in plants.

Symplastic intercellular transport in plants is achieved by plasmodesmata (PD). These cytoplasmic channels are well known to interconnect plant cells to facilitate intercellular movement of water, nutrients, and signaling molecules including hormones. However, it is not known whether Al may affect this cell-to-cell transport process, which is a critical feature for roots as organs of nutrient/water uptake. We have microinjected the dye lucifer yellow carbohydrazide into peripheral root cells of an Al-sensitive wheat (Triticum aestivum cv Scout 66) either before or after Al treatment and followed the cell-to-cell dye-coupling through PD. Here we show that the Al-induced root growth inhibition is closely associated with the Al-induced blockage of cell-to-cell dye coupling. Immunofluorescence combined with immuno-electron microscopic techniques using monoclonal antibodies against 1-->3-beta-D-glucan (callose) revealed circumstantial evidence that Al-induced callose deposition at PD may responsible for this blockage of symplastic transport. Use of 2-deoxy-D-glucose, a callose synthesis inhibitor, allowed us to demonstrate that a reduction in callose particles correlated well with the improved dye-coupling and reduced root growth inhibition. While assessing the tissue specificity of this Al effect, comparable responses were obtained from the dye-coupling pattern in tobacco (Nicotiana tabacum) mesophyll cells. Analyses of the Al-induced expression of PD-associated proteins, such as calreticulin and unconventional myosin VIII, showed enhanced fluorescence and co-localizations with callose deposits. These results suggest that Al-signal mediated localized alterations to calcium homeostasis may drive callose formation and PD closure. Our data demonstrate that extracellular Al-induced callose deposition at PD could effectively block symplastic transport and communication in higher plants.

Molecular cloning and immunohistochemical localization of rat dipeptidyl peptidase III.

Dipeptidyl peptidase III (DPP III) was purified to homogeneity from rat liver cytosol. The calculated molecular weight of the purified enzyme was 82845.6 according to TOF-MS, and 82000 on non-denatured PAGE and 82000 on SDS-PAGE in the absence or presence of beta-ME. These findings suggest that the enzyme assumes a monomeric form in rat liver cytosol. The enzyme rapidly hydrolyzed the substrate Arg-Arg-MCA and moderately hydrolyzed Ala-Arg-MCA in a pH range of 7. 5 to 9.5. The K(in), K(cat) and K(cat)/K(m) values of DPP III at optimal pH (pH 8.5) were 290 microM, 18.0 s(-1) and 6.21x10(4) s(-1)M(-1) for Arg-Arg-MCA and 125 microM, 4.53 s(-1) and 3.62x10(4) s(-1)M(-1) for Ala-Arg-MCA, respectively. DPP III was potently inhibited by EDTA, 1,10-phenanthroline, DFP, PCMBS, NEM, beta-ME and iodoacetamide. Furthermore, we screened a rat liver cDNA library using affinity-purified anti-rat DPP III rabbit IgG, and we determined the cDNA structure and deduced the amino acid sequence. The cDNA designated as lambdaRDIII-11 is composed of 2640 bp of nucleotides in length and encodes 738 amino acids in the coding region. Although the enzyme has a novel zinc-binding motif, HEXXXH in structure, DPP III is thought to belong to family 1 in clan MA in the metalloprotease kingdom. These findings suggest that DPP III is a metalloprotease that is probably regulated by SH modification. The DPP III antigen was extensively detected in the cytosol of various rat tissues by the immunohistochemical examination of the protein.

Regulation of vitamin D-1alpha-hydroxylase and -24-hydroxylase expression by dexamethasone in mouse kidney.

We investigated the effects of dexamethasone on vitamin D-1alpha-hydroxylase and -24-hydroxylase expression and on vitamin D receptor (VDR) content in the kidneys of mice fed either a normal (NCD) diet or a calcium- and vitamin D-deficient (LCD) diet for 2 weeks. For the last 5 days mice received either vehicle or dexamethasone (2 mg/kg per day s.c.). Dexamethasone significantly increased plasma calcium concentrations without changing plasma concentrations of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) in both NCD and LCD groups. Northern blot and enzyme activity analyses in NCD mice revealed that dexamethasone increased renal VDR mRNA expression modestly and greatly increased 24-hydroxylase mRNA abundance and enzyme activity, but did not affect 1alpha-hydroxylase mRNA abundance and enzyme activity. In mice fed an LCD diet, dexamethasone increased renal VDR mRNA expression 1.5-fold, decreased 1alpha-hydroxylase mRNA abundance (52%) and activity (34%), and markedly increased 24-hydroxylase mRNA abundance (16-fold) and enzyme activity (9-fold). Dexamethasone treatment did not alter functional VDR number (B(max) 125-141 fmol/mg protein) or ligand affinity (K(d) 0.13-0.10 nM) in LCD mice. Subcutaneous injections of 1,25(OH)(2)D(3) (0.24 nmol/kg per day for 5 days) into NCD mice strongly increased renal 24-hydroxylase mRNA abundance and enzyme activity, while there was no effect of dexamethasone on renal 24-hydroxylase expression in these mice. This may be due to overwhelming induction of 24-hydroxylase by 1,25(OH)(2)D(3). These findings suggest that glucocorticoid-induced osteoporosis is caused by direct action of the steroids on bone, and the regulatory effect of glucocorticoids on renal 25-hydroxyvitamin D(3) metabolism may be less implicated in the initiation and progression of the disease.

Effects of light on the tritrophic interaction between kidney bean plants, two-spotted spider mites and predatory mites, Amblyseius womersleyi (Acari: Phytoseiidae).

By analyzing the volatiles from Tetranychus urticae-infested kidney bean plants (Phaseolus vulgaris) at different times for two days, we found that they were mainly produced in the light. Tetranychus urticae showed a higher oviposition rate and spent more time feeding during the day (in the light) than at night (in the dark). Infested leaves placed in the light attracted the predatory mite Amblyseius womersleyi, whereas those that were placed in the dark for at least 2 h in daytime did not. This indicates that presence or absence of light affects the production of herbivore-induced plant volatiles. Amblyseius womersleyi dispersed more frequently and consumed more T. urticae eggs during the day (in the light) than at night (in the dark), whereas their oviposition rate did not differ between day and night. Presence or absence of herbivore-induced plant volatiles in the surroundings did not affect dispersal, predation or oviposition rates of A. womersleyi. These results show that A. womersleyi's behavior coincides with the production pattern of herbivore-induced plant volatiles.

Involvement of growth-related protein in lipopolysaccharide-induced rabbit arthritis: cooperation between growth-related protein and IL-8, and interrelated regulation among TNFalpha, IL-1, IL-1 receptor antagonist, IL-8, and growth-related protein.

We investigated the functional role of a CXC chemokine, growth-related protein (GRO), in the recruitment of neutrophils in lipopolysaccharide (LPS)-induced rabbit arthritis. The amounts of GRO in the synovial fluids (SF) reached the first peak (major) at 2 hours and the second peak (minor) at 9 hours after injection of LPS into the knee joints. Administration of anti-GRO mouse monoclonal antibody inhibited 54% of the peak leukocyte accumulation at 9 hours (neutrophils greater than 95%), which was similar to the inhibition by anti-IL-8 IgG (48%). Co-administration of these inhibitors increased the inhibition up to 70% at 9 hours and also inhibited 65% of the initial phase of leukocyte infiltration at 2 hours (neutrophils greater than 99%), which was not affected by a single administration of each inhibitor. The amounts of GRO in SF at 2 hours were not altered by either anti-TNFalpha mAb or anti-IL-8 IgG, but reduced by rabbit recombinant IL-1 receptor antagonist (rrlL-1Ra) by 39%. The inhibition by rrlL-1 Ra was augmented further to 59% with coadministered anti-TNFalpha mAb. In contrast, the amounts of GRO at 9 hours were reduced by rrlL-1Ra by 67%. There was no additional reduction in the amounts of GRO at 9 hours by either combination of rrlL-1Ra with anti-TNFalpha mAb or anti-IL-8 IgG. Administration of anti-GRO mAb did not alter TNFalpha or IL-8 contents in SF at their peak (2 hours), but reduced the amounts of IL-1beta at 6 hours and IL-1Ra at 9 hours by 42% and 49%, respectively. These results provide evidence for the following: (a) GRO as well as IL-8 are important mediators involved in the recruitment of neutrophils both in the early and the late phase of LPS-induced arthritis, (b) IL-1 produced in the early phase stimulates GRO production, (c) GRO plays a role in the later induction of IL-1beta and IL-1Ra, and (d) induction of GRO is not regulated by IL-8.

Intraoperative enzyme-amperometric monitoring of extracellular glutamate concentration with a dialysis electrode in ischemic human brain.

Changes in the extracellular concentration of glutamate in the brain ([Glu]e) were monitored continuously by an enzyme-amperometric technique employing a dialysis electrode during ischemia caused by isolation of the brain tissue in rats and human patients. In the rat (n = 10), the dialysis electrode was placed in the frontal cortex and the frontal lobe was transected. A transient sharp increase in [Glu]e was frequently observed during the transection. A biphasic elevation (a rapid increase followed by a slowly continuing increase) subsequently occurred with a latent period of 1-3 min after the transection of the rat frontal lobe. In patients (n = 7), the dialysis electrode was placed in tumor-free cortical areas which were planned to be resected together with gliomas. Progressive increases in [Glu]e were observed in all of the patients as the isolation of the brain tissue progressed. A biphasic increase, similar to that seen in the rat, was identified in 2 patients in whom the cortical area surrounding the dialysis electrode was rapidly isolated. The present enzyme-amperometric technique employing a dialysis electrode appears to be useful for detecting the occurrence of potentially harmful ischemia and for securing minimal metabolic stress caused during various surgical manipulations.

Dipeptidyl peptidase III from rat liver cytosol: purification, molecular cloning and immunohistochemical localization.

Dipeptidyl peptidase III (DPP III) was purified to homogeneity from rat liver cytosol. The calculated molecular weight of the purified enzyme was 82845.6 according to TOF-MS and 82000 on non-denaturing PAGE, and 82000 on SDS-PAGE in the absence or presence of beta-mercaptoethanol. These findings suggest that the enzyme exists in a monomeric form in rat liver cytosol. The enzyme rapidly hydrolyzed the substrate Arg-Arg-MCA and moderately hydrolyzed Gly-Arg-MCA in the pH range of 7.5 to 9.5. The Km, k(cat) and k(cat)/Km values of DPP III at optimal pH (pH 8.5) were 290 microM, 18.0 s(-1) and 62.1 s(-1) x nM(-1) for Arg-Arg-MCA and 125 microM, 4.53 s(-1) and 36.2 s(-1) x nM(-1) for Ala-Arg-MCA, respectively. DPP III was potently inhibited by EDTA, 1,10-phenanthroline, DFP, PCMBS and NEM. These findings suggest that DPP III is an exo-type peptidase with characteristics of a metallo- and serine peptidase. For further information on the molecular structure, we screened a rat liver cDNA library using affinity-purified anti-rat DPP III rabbit IgG antibodies, determined the cDNA structure and deduced the amino acid sequence. The cDNA, designated as lambdaRDIII-11, is composed of 2640 bp and encodes 738 amino acids in the coding region. Although the enzyme has a novel zinc-binding motif, HEXXXH, DPP III is thought to belong to family 1 in clan MA in the metalloprotease kingdom. The DPP III antigen was detected in significant amounts in the cytosol of various rat tissues by immunohistochemical examination.

Alcohol consumption enhances liver metastasis in colorectal carcinoma patients.

BACKGROUND: It is important to identify risk factors for liver metastasis in patients with colorectal carcinoma because the liver is the most common site of recurrence. Alcohol consumption reportedly is associated with hematogenous metastasis in certain animal models. Furthermore, some studies have shown that carmofur, a derivative of 5-fluorouracil, is particularly effective as adjuvant chemotherapy for colorectal carcinoma, and may even suppress liver metastasis, although the mechanism by which this occurs remains unknown. In addition, carmofur is known to inhibit alcohol metabolism. To the authors' knowledge, the relation between liver metastasis in colorectal carcinoma and alcohol consumption has not been examined previously. Therefore, the authors studied the relations between liver metastasis in colorectal carcinoma and various clinicopathologic factors including alcohol consumption status. METHODS: This study was comprised of 133 colorectal carcinoma patients with invasion beyond the submucosal layer who had undergone surgical resection. The subjects were examined and divided into two groups according to the occurrence or absence of liver metastasis. The relations between liver metastasis and other clinicopathologic factors were analyzed by univariate and multivariate statistical methods. RESULTS: Univariate analysis showed alcohol consumption (P=0.0021) and blood vessel invasion (P=0.0045) were correlated with liver metastasis. Multivariate analysis showed both to be independent risk factors for liver metastasis. CONCLUSIONS: Alcohol consumption is an independent risk factor for liver metastasis in colorectal carcinoma patients. Therefore, patients with colorectal carcinoma who drink alcohol require intensive examination and follow-up with respect to liver metastasis. Further study is necessary to confirm the effect of adjuvant chemotherapy using carmofur in colorectal carcinoma patients.

Production and regulation of monocyte chemoattractant protein-1 in lipopolysaccharide- or monosodium urate crystal-induced arthritis in rabbits: roles of tumor necrosis factor alpha, interleukin-1, and interleukin-8.

The production of monocyte chemoattractant protein-1 (MCP-1) and its regulation by TNFalpha, IL-1, and IL-8 were investigated in two rabbit models of arthritis induced by intra-articular injection of lipopolysaccharide (LPS) or monosodium urate (MSU) crystals. We first prepared recombinant rabbit MCP-1 and antibodies and then developed an immunoassay. The immunoassay detected 3 pg/ml rabbit MCP-1 and did not cross-react with other rabbit chemokines such as IL-8 or GRO. MCP-1 was first detected in synovial fluid (SF) at 1 hour, and peaked at 4 or 2 hours after the injection of LPS or MSU crystals, respectively. Immunohistochemically, MCP-1 was detected in synovial lining cells and infiltrating neutrophils. The amounts of MCP-1 detected in SF from neutrophil-depleted rabbits were similar to those in normal rabbits, suggesting that synovial lining cells were the main source of MCP-1 detected in SF. The peak level of MCP-1 in SF after LPS-injection was inhibited by 57% with anti-TNFalpha mAb and by 41% with IL-1 receptor antagonist (IL-1Ra). Coadministration of anti-TNFalpha mAb and IL-1Ra inhibited 90% of MCP-1 production. In contrast, the peak level of MCP-1 in SF after MSU crystal-injection was not affected by any cytokine inhibitor, but was reduced by 52% with coadministration of anti-TNFalpha mAb and IL-1Ra. Anti-IL-8 IgG had no effect on the production of MCP-1 in either model. Thus, the production of MCP-1 in LPS-induced arthritis was mostly regulated by TNFalpha and IL-1, whereas half the extent of MCP-1 production in MSU crystal-induced arthritis was independent of TNFalpha or IL-1. IL-8 does not seem to regulate the production of MCP-1 in SF either directly or indirectly. Finally, administration of neutralizing anti-MCP-1 antibody inhibited LPS- and MSU crystal-induced monocyte infiltration by 58.4% and 44.9%, respectively, suggesting that synovial production of MCP-1 plays an important role in the recruitment of monocytes in these arthritis models.

Analysis of the cytokine network among tumor necrosis factor alpha, interleukin-1beta, interleukin-8, and interleukin-1 receptor antagonist in monosodium urate crystal-induced rabbit arthritis.

In the present study, we analyzed the cytokine network among TNFalpha, IL-1beta, IL-8, and IL-1 receptor antagonist (IL-1Ra) in a rabbit experimental model of acute gout. The production of TNFalpha in synovial fluids reached the peak at 2 hours after the intra-articular injection of monosodium urate (MSU) crystals. The production of IL-1beta and IL-8 reached the first peak at 2 hours and the second peak at 9 and 12 hours, respectively. The production of endogenous IL-1Ra reached the peak at 9 hours. The source of TNFalpha and the first phase of IL-8 was synovial cells, whereas infiltrating leukocytes were the source of the second phase of IL-8 and also of IL-1beta and IL-1Ra. The production of TNFalpha was not altered by either anti-lL-8 IgG or IL-1Ra. The first IL-1beta peak was reduced only with a combination of anti-TNFalpha mAb and anti-lL-8 IgG, whereas the second peak was significantly reduced by either inhibitor. The first IL-8 peak was not altered with anti-TNFalpha mAb or IL-1 Ra, whereas the second IL-8 peak was reduced with IL-1Ra. Anti-TNFalpha mAb or anti-lL-8 IgG significantly reduced the peak level of endogenous IL-1Ra. These cytokine inhibitors also attenuated the maximal leukocyte accumulation at 9 hours, but not the initial phase, which occurred within 2 hours. These results provide evidence that IL-8 and TNFalpha were responsible for the production of IL-1beta and IL-1Ra, and that IL-1beta was responsible for the second phase of IL-1beta and IL-8 production. Our data also suggest that the initial and the maximal phases of leukocyte influx are differently regulated. Finally, the intravenous injection of colchicine inhibited neutrophil infiltration without affecting the production of TNFalpha or the first peak of IL-8, suggesting that colchicine inhibits MSU crystal-induced arthritis by directly inhibiting the migration of neutrophils.

Blockade of ATP-sensitive K+ channels attenuates preconditioning effect on myocardial metabolism in swine: myocardial metabolism and ATP-sensitive K+ channels.

OBJECTIVE: We investigated if blockade of ATP-sensitive K+ channels (KATP) abolishes the protective effect of ischemic preconditioning (IP) on myocardial metabolism and ischemia-induced reactive hyperemia (RH) in pigs. METHODS: IP was elicited by a single cycle of 5 min occlusion and 5 min reperfusion of coronary artery, followed by 15 min of test ischemia and 120 min of reperfusion. Vehicle or the ATP-sensitive K+ channels (KATP) blocker, glibenclamide (3 or 6 mg/kg; G3 or G6) was administered before IP (groups; IP, G3+IP, G6+IP). As respective controls, the same treatment was performed in groups without IP (groups; C, G3, G6). Tissue levels of ATP, creatine phosphate (CP) and intracellular pH (pHi) in the area at risk were measured by 31P-nuclear magnetic resonance spectroscopy. RH after 5 min of preconditioning ischemia was assessed by regional myocardial blood flow. RESULTS: ATP and pHi were preserved after 15 min of ischemia in the IP group [C/IP; ATP=57+/-4/76+/-10% of baseline, pHi=6.18+/-0.08/6.66+/-0.03, P<0.05, C vs. IP]. Both doses of glibenclamide completely abolished the ATP sparing effect of IP. The high dose completely abolished pHi preservation (G6+IP=6.33+/-0.06), while the low dose showed only a partial effect (G3+IP=6.48+/-0.03). Glibenclamide did not adversely affect myocardial metabolism in groups without IP. Glibenclamide attenuated RH after 5 min of ischemia by 30% in both subendocardium and subepicardium. CONCLUSIONS: Blockade of KATP abolished the preconditioning effect on myocardial metabolism, and partially attenuated post-ischemic reactive hyperemia in pigs. These results indicate that KATP activation might be involved in the mechanisms of these phenomena, reactive hyperemia is not sufficient to induce IP protection.

A case of acquired zinc deficiency in a mature breast-fed infant.

We describe a 5-month-old Japanese infant with zinc deficiency, who was exclusively breast-fed and showed improvement after zinc supplement was administered. His serum zinc level and the zinc content of breast milk from his mother were extremely low, although the mother's serum zinc level was within normal limits. Zinc deficiency would not be latently uncommon in a mature breast-fed infant.