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A 69-year-old man with diabetes mellitus was diagnosed with a prostate abscess. Although the pathogen was fluoroquinolone-resistant Escherichia coli and the oral administration of trimethoprim-sulfamethoxazole was initiated, the infection recurred after three months. The antibiotic therapy was subsequently changed to intravenous fosfomycin, and the patient's condition promptly improved. Four weeks of fosfomycin therapy was successfully continued without any adverse events. In the era of antibiotic resistance, revival of forgotten drugs is an important issue for clinicians. Fosfomycin can be applied as an alternative option for prostate infections, considering the remaining susceptibility of multidrug-resistant pathogens to fosfomycin and the good pharmacokinetics of this drug in prostatic tissue.

We describe a rare case of recurrent Stenotrophomonas maltophilia bacteremia in a previously healthy 45-year-old man. The infection was caused by osteomyelitis at the site of an iliac crest bone graft harvest. A genetic analysis using enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) revealed that the blood isolates and pathogens obtained from the surgical wound were identical. Initial treatment with levofloxacin and cefozopran was ineffective, but the patient's infection was successfully treated by long-term administration of latamoxef and trimethoprim-sulfamethoxazole. The present case suggests that attention should be given to the possibility of S. maltophilia infection in any situations.

Acute generalized exanthematous pustulosis (AGEP) is a self-limiting type of drug eruption that frequently occurs as a reaction to antibiotics, particularly penicillins or macrolides. Daptomycin (DAP) is a newly developed antibiotic that specifically targets methicillin-resistant Staphylococcus aureus infection. We herein present the case of a 77-year-old severe burn victim who was diagnosed with DAP-induced AGEP while receiving treatment in an intensive care unit. Although rare, physicians should be aware that the administration of DAP can cause AGEP, which may complicate the clinical course of patients with a high fever and inflammation.

Methicillin-resistant Staphylococcus aureus is still a great concern, and recognition of the carrier is essential for appropriate infection control in intensive care units. The utility of wet swab compared to dry swab as an intranasal screening test has not been well assessed yet. A comparative study of the wet and dry swab in its ability to detect the organism was performed against critically ill patients, and it was found that there were no statistically significant differences between the two different methods. The wet swab did not show increased sensitivity compared to dry one.

A 38-year-old woman was admitted to our hospital because she experienced cardiopulmonary arrest at her wedding;her cardiac beats were resumed 20 min after cardiopulmonary resuscitation performed by her relatives and hotel staffs. Enhanced computed tomography revealed acute aortic redissection in chronic dissecting aneurysm in the right sinus of Valsalva, which was believed to have occurred in the 4th month of pregnancy 2 years before. Echocardiography showed moderate aortic regurgitation. We performed aortic valve-sparing operation and ascending aortic replacement with partial remodeling of the right sinus of Valsalva. She returned to work 2 months later without high-order dysfunction.

Varicella-zoster virus (VZV) usually causes localized zoster in adults. However, in immunocompromised patients, it can cause systemic infection accompanied by complications such as pneumonia, encephalitis, and hepatitis. Although most of critically ill patients in intensive care unit (ICU) are immunologically compromised, they are usually not considered to be at risk for systemic VZV infection.We report two cases of systemic VZV infection occurring in critically ill patients in an ICU. One patient was a 69-year-old man with Streptococcus pneumoniae-induced purpurafulminans, and the other was a 75-year-old woman with severe acute pancreatitis. During the clinical course in the ICU, characteristic vesicles with umbilical fossa appeared diffusely and bilaterally on their face, trunk, and extremities. VZV-specific IgG levels were confirmed to be elevated compared to that of the pre-onset, and a diagnosis of recurrent VZV infection was made in both patients. The patients were treated at the same ICU but did not coincide with each other; therefore a cross-infection was unlikely. They were treated with intravenous acyclovir, but the latter patient eventually died of respiratory failure.VZV infection can cause a number of serious complications, and can lead to death in some patients. Early detection and proper treatment are needed to prevent the infection from spreading out and save the patients. It might be necessary to consider antiviral prophylaxis against VZV infection for a part of critically ill patients in ICU, although the effectiveness of this approach is yet to be established.

This report focuses on 3 cases of traumatic aortic dissection or rupture at the isthmus. We selected 3 different methods of treatment. In the 1st case, we performed an emergency operation with graft replacement of the proximal descending aorta. In the 2nd case, we performed elective graft replacement 5 months after the rupture under careful blood pressure control. Thirdly, we performed emergency stent grafting at the isthmus, the rupture site. All cases were successfully treated, but it remains difficult to select the method of treatment for multisystem disorder. Our current strategy for traumatic rupture at the isthmus is immediate stent grafting. It will also be a very useful procedure for multisystem trauma.

The clinical picture of Ochrobactrum anthropi infection is not well described because the infection is rare in humans and identification of the pathogen is difficult. We present a case of O. anthropi bacteremia that was initially misidentified as Ralstonia paucula and later identified by 16S rRNA sequencing and recA analysis.

A 46-year-old woman was transferred to our emergency unit because of impaired consciousness and respiratory failure with the history of excessive pesticide intake. The patient was hypersalivative and had bilateral pupillary miosis. Laboratory results showed markedly decreased cholinesterase. She was intubated and treated in the intensive care unit with the diagnosis of organophosphorus poisoning. The patient had persisted diarrhea, with a high fever and stomach tenderness on day 10. Whole-body contrast enhanced computed tomography revealed a swollen, enhanced small intestinal wall, and blood culture identified Delftia acidovorans. She was diagnosed as D. acidovorans bacteremia, probably caused by bacterial translocation based on the clinical presentation and the exclusion of other sources, and treated well with a total of 8 days of antibiotic therapy. So far as we know, this is the first case of D. acidovorans bacteremia that was presumably caused by bacterial translocation after organophosphorus poisoning in an immunocompetent adult patient.

A 95-year-old man with chronic obstructive pulmonary disease and chronic hepatitis C virus infection was treated for acute lung injury caused by Chlamydophila pneumoniae with antibiotics and high-dose corticosteroids. In total, 7,500 mg methylprednisolone and 680 mg prednisolone were administered over 21 days. However, respiratory failure progressed, and chest computed tomography (CT) scan showed bilateral ground-glass opacity and cavity-forming consolidation in the right upper lobe. Despite intensive therapy, the patient died of multiple organ failure on day 7. CT-guided necropsy was performed, and pathological examination revealed invasive pulmonary aspergillosis and Pneumocystis jirovecii pneumonia. Invasive pulmonary aspergillosis and P. jirovecii pneumonia are both life-threatening opportunistic fungal infections. Co-infection of these organisms is rare but possible if the patient is in an extremely immunocompromised state. Short-term but high-dose systemic corticosteroid therapy was considered to be the risk factor in this case. We should pay more attention to immunocompromised hosts who might be suffering from co-infection of opportunistic infections. Moreover, we need to consider preventive measures in such high-risk cases.

An 88-year-old man died of streptococcal toxic shock syndrome due to a group G streptococcus infection that was possibly caused by an intramuscular injection given 30 hours earlier in his right deltoid muscle. The causative pathogen was later identified to be Streptococcus dysgalactiae subsp. equisimilis (stG485). Although providing intramuscular injections is an essential skill of health care workers that is performed daily worldwide, it may constitute a port of entry for pathogens via skin breaches that can cause life-threatening infections. All invasive procedures should be carefully performed, especially when immunologically compromised patients are involved.

An emphysematous liver abscess is a fatal condition that often occurs in patients with uncontrolled diabetes mellitus. I herein describe two cases of Klebsiella pneumoniae-induced emphysematous liver abscesses complicated by septic pulmonary emboli in patients with poorly controlled diabetes mellitus. Both patients showed hemoglobin A1c levels of more than 10% and did not present with any abdominal symptoms on admission. However, they were diagnosed and successfully treated with percutaneous transhepatic abscess drainage and antibiotics. This fatal disease should be taken into consideration in patients with uncontrolled diabetes mellitus who suffer from prolonged fevers and uncharacteristic general malaise.

We herein report the case of an 85-year-old woman presenting with right internal jugular vein candidal thrombophlebitis associated with central venous catheters (CTCVC). The infecting agent was Candida albicans, which caused recurrent candidemia five times in total. Micafungin (MCFG) alone was ineffective; however, the combination of MCFG with fosfluconazole (F-FLCZ) successfully treated the patient without a need for any anticoagulant or surgical therapies. To the extent of our knowledge, this is the first report of CTCVC being successfully treated with a combination of F-FLCZ and MCFG. These new antifungal agents have better efficacy, tolerability and bioavailability; therefore, they can be useful alternatives to classical combination therapies such as amphotericin-B and 5-fluorocytosine.

A 73-year-old man with long-term food deprivation and total parenteral nutrition was diagnosed with septic pulmonary emboli (SPE) and a persistent bacteremia caused by central line-associated blood stream methicillin-resistant Staphylococcus aureus (MRSA) infection. Although daptomycin (DAP) failed to treat the persistent bacteremia, linezolid successfully controlled it. DAP is inactivated by lung surfactant, and therefore, it should not be administered for lower respiratory infections. However, SPE caused by MRSA has been reported to be treatable with DAP since it is an infection of the lung parenchyma. We herein report the lack of effect of daptomycin in SPE treatment.

ONO-4641 is a next-generation sphingosine 1-phosphate (S1P) receptor agonist selective for S1P receptors 1 and 5. The objective of the study was to characterize the immunomodulatory effects of ONO-4641 using preclinical data. ONO-4641 was tested in both in-vitro pharmacological studies as well as in-vivo models of transient or relapsing-remitting experimental autoimmune encephalomyelitis (EAE). In vitro, ONO-4641 showed highly potent agonistic activities versus S1P receptors 1 and 5 [half maximal effective concentration (EC(50) ) values of 0·0273 and 0·334 nM, respectively], and had profound S1P receptor 1 down-regulating effects on the cell membrane. ONO-4641 decreased peripheral blood lymphocyte counts in rats by inhibiting lymphocyte egress from secondary lymphoid tissues. In a rat experimental autoimmune encephalomyelitis (EAE) model, ONO-4641 suppressed the onset of disease and inhibited lymphocyte infiltration into the spinal cord in a dose-dependent manner at doses of 0·03 and 0·1 mg/kg. Furthermore, ONO-4641 prevented relapse of disease in a non-obese diabetic mouse model of relapsing-remitting EAE. These observations suggest that ONO-4641 may provide therapeutic benefits in the treatment of multiple sclerosis., (© 2012 ONO Pharmaceutical Co., Ltd Clinical and Experimental Immunology © 2012 British Society for Immunology.)

An 86-year-old woman with diabetes mellitus and severe decubitus at the sacral and calcaneal regions stemming from poor daily activity was diagnosed with pyometra perforation caused by Actinomyces. No foreign materials, including an IUD, were found inside the uterus. Pyometra is usually caused by Enterobacteriaceae or anaerobes derived from the gastrointestinal tract. The virulence of Actinomyces is rather low, and, in almost all the reported cases of Actinomyces-related pyometra, an intrauterine device (IUD) was involved. Although rare, Actinomyces may be ascribed as a virulent pathogen that causes pyometra in the absence of foreign materials.

A 64-year-old man with a 10-year history of palmoplantar pustulosis, a recent history of cranial surgery and a persistent upper airway infection presented with a high fever and deep coma. The patient was diagnosed with Group A Streptococcal meningitis and promptly treated with antibiotics. Although his general condition recovered well, sensorineural hearing loss and facial palsy remained. Group A Streptococcal meningitis is a rare condition, and its typical clinical picture and epidemiological features remain poorly understood. Physicians need to be more aware of this infection, which is extremely rare but frequently causes various complications and yields a high mortality.

We herein present the case of a 69-year-old Japanese man who had unprotected sexual contact with a local commercial sex worker in an East Asian country and was diagnosed as having disseminated gonococcal infection (DGI). The organism was confirmed to be Neisseria gonorrhoeae based on 16S rRNA sequencing and positive results for the cppB gene. This case indicates that a diagnosis of DGI should also be considered in elderly individuals. DGI potentially causes many complications, and the pathogen has recently been reported to be resistant to various antibiotics. Physicians must therefore pay more attention to the possible occurrence of DGI in various clinical settings.

Many butterflies acquire nutrients from non-nectar sources such as puddles. To better understand how male Papilio butterflies identify suitable sites for puddling, we used behavioral and electrophysiological methods to examine the responses of Japanese Papilio butterflies to Na(+), K(+), Ca(2+), and Mg(2+). Based on behavioral analyses, these butterflies preferred a 10-mM Na(+) solution to K(+), Ca(2+), and Mg(2+) solutions of the same concentration and among a tested range of 1 mM to 1 M NaCl. We also measured the ion concentrations of solutions sampled from puddling sites in the field. Na(+) concentrations of the samples were up to 6 mM, slightly lower than that preferred by butterflies in the behavioral experiments. Butterflies that sipped the 10 mM Na(+) solution from the experimental trays did not continue to puddle on the ground. Additionally, butterflies puddled at sites where the concentrations of K(+), Ca(2+), and/or Mg(2+) were higher than that of Na(+). This suggests that K(+), Ca(2+), and Mg(2+) do not interfere with the detection of Na(+) by the Papilio butterfly. Using an electrophysiological method, tip recordings, receptor neurons in contact chemosensilla inside the proboscis evoked regularly firing impulses to 1, 10, and 100 mM NaCl solutions but not to CaCl(2) or MgCl(2). The dose-response patterns to the NaCl solutions were different among the neurons, which were classified into three types. These results showed that Japanese Papilio butterflies puddle using Na(+) detected by the contact chemosensilla in the proboscis, which measure its concentration.

Background: In small bowel transplantation (SBTx), inhibition of both graft-versus-host disease (GVHD) and allograft rejection is necessary., Methods: We investigated the potency of a new sphingosine-1-phosphate receptor agonist, W-061, for these two immune responses in SBTx. W-061 has a completely different molecular structure from FTY720. Heterotopic SBTx was performed from Wistar-Furth (WF) into (WF×ACI) F1 rats as a GVHD model or F1 to WF rats as a rejection model. Recipients were orally given 3 mg/kg/day W-061 for 14 days after SBTx. Recipient survival, body weight, histopathology, lymphocyte subpopulations, and the cytokine profile were evaluated., Results: W-061 treatment significantly prolonged graft survival over 100 days in four out of six recipients in the GVHD group and over 60 days in three out of six recipients in the rejection group. W-061 strongly inhibited GVHD and rejection as seen histopathologically in comparison with untreated control rats. W-061 caused a significant reduction in donor-derived T cells in target organs and infiltrating T cells in allografts by promoting these cells to home into the secondary lymphoid tissues and sequestrating those cells there. W-061 significantly decreased production of interferon-γ in target organs and allografts., Conclusion: Therefore, these data suggest that W-061 has considerable potential as a new therapeutic immunosuppressant in patients with SBTx., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)

Structure-activity relationship (SAR) of sphingosine-1-phosphate receptor agonists with a dihydronaphthalene scaffold was investigated. Compound 1 was modified to improve S1P(1) agonistic activity and in vivo peripheral lymphocyte lowering (PLL) activity without impairing selectivity over S1P(3) agonistic activity. A detailed SAR study of the terminal lipophilic part revealed that the introduction of substituents on the propylene linker and the terminal benzene ring influences in vitro and PLL activities. Compound 6n bearing a (S)-methyl group at the 2-position on the propylene linker and chlorine at the para-position on the terminal benzene ring showed potent hS1P(1) agonistic activity with excellent selectivity over hS1P(3) and in vivo PLL activity in mice., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The infection caused by non-b-type Haemophilus influenzae has been increasing in this Hib (H.influenzae serotype b) vaccination era. H.influenzae serotype f (Hif) is considered as one of those emerging pathogens. In general, H.influenzae is a common pathogen of such as pneumonia, otitis media, and meningitis, but is rare in soft tissue infection, especially at the extremity. We report a rare case of severe soft tissue infection caused by Hif which occurred at the lower extremity of immunocompetent adult patient.

A 21-year-old Japanese man with a history of marked body weight loss over a short period of time died of necrotizing duodenitis caused by Clostridium perfringens (C. perfringens) type A. C. perfringens type A is considered to usually cause self-limiting gastroenteritis. Necrotizing enteritis sometimes occurs due to C. perfringens in developing countries; however, it is primarily caused by the type C strain and its site of onset is typically the jejunum or ileum. This is a rare case of necrotizing duodenitis caused by C. perfringens type A in a Japanese young man. Physicians need to be more aware of this emerging fatal disease in developed countries.

Structure-activity relationship of sphingosine-1-phosphate receptor agonists was examined. Cinnamyl derivative 1 was modified to improve S1P(1) agonistic activity as well as selectivity over S1P(3) agonistic activity. Dihydronaphthalene derivative 10d was identified as a potent S1P(1) receptor agonist with high selectivity against S1P(3) and enhanced efficacy in lowering peripheral lymphocyte counts in mice., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Structure-activity relationship of sphingosine-1-phosphate receptor agonist was examined. In terms of reducing the flexibility of molecule, hit compound 1 was modified to improve S1P(1) agonistic activity as well as selectivity over S1P(3) agonistic activity. Novel S1P agonists with cinnamyl scaffold or 1,2,5,6-tetrahydropyridine scaffold were identified., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Although IL-17 is a pro-inflammatory cytokine reportedly involved in various autoimmune inflammatory disorders, its role remains unclear in murine models of colitis. Acute colitis was induced by 2.5% dextran sodium sulfate (DSS) treatment for 5 days. A novel sphingosine-1-phosphate receptor agonist W-061, a prototype of ONO-4641, was orally administered daily, and histopathological analysis was performed on the colon. The number of lymphocytes and their cytokine production were also evaluated in spleen, mesenteric lymph node, Peyer's patch and lamina propria of the colon. Daily administration of W-061 resulted in improvement of DSS-induced colitis, and significantly reduced the number of CD4+ T cells in the colonic lamina propria. Numbers of both Th17 and Th1 cells were reduced by W-061 treatment. W-061, however, had no influence on the number of Treg cells in lamina propria. Thus, Th17 and Th1 cells in lamina propria were thought to be the key subsets in the pathogenesis of DSS-induced colitis. In conclusion, W-061 may be a novel therapeutic strategy to ameliorate acute aggravation of inflammatory bowel diseases.

Leukotriene B(4), an arachidonate metabolite, is a potent chemoattractant of leukocytes involved in various inflammatory diseases. Two G-protein-coupled receptors for leukotriene B(4) have been cloned and characterized. BLT1 (Yokomizo, T., Izumi, T., Chang, K., Takuwa, Y., and Shimizu, T. (1997) Nature 387, 620-624) is a high affinity receptor exclusively expressed in leukocytes, and BLT2 (Yokomizo, T., Kato, K., Terawaki, K., Izumi, T., and Shimizu, T. (2000) J. Exp. Med. 192, 421-432) is a low affinity receptor expressed more ubiquitously. Here we report the binding profiles of various BLT antagonists and eicosanoids to either BLT1 or BLT2 using the membrane fractions of Chinese hamster ovary cells stably expressing the receptor. BLT antagonists are grouped into three classes: BLT1-specific U-75302, BLT2-specific LY255283, and BLT1/BLT2 dual-specific ZK 158252 and CP 195543. We also show that 12(S)-hydroxyeicosatetraenoic acid, 12(S)-hydroperxyeicosatetraenoic acid, and 15(S)-hydroxyeicosatetraenoic acid competed with [(3)H]LTB(4) binding to BLT2, but not BLT1, dose dependently. These eicosanoids also cause calcium mobilization and chemotaxis through BLT2, again in contrast to BLT1. These findings suggest that BLT2 functions as a low affinity receptor, with broader ligand specificity for various eicosanoids, and mediates distinct biological and pathophysiological roles from BLT1.

Rat pineal gland contains a 12-lipoxygenase as demonstrated by the enzyme activity, RNA blot analysis and in situ hybridization. Using rats maintained with 12-h dark and light cycles, dynamic changes of the enzyme in pineal gland were examined. When the crude extract of pineal glands was incubated with arachidonic acid and the reaction products were analyzed by reverse-phase HPLC, the glands obtained from rats in the dark showed a higher 12-lipoxygenase activity than those obtained from rats in the light. The pineal 12-lipoxygenase activity decreased after the light was on at 7 o'clock and reached the lowest level around 16 o'clock. Upon Western blot analysis the amount of 12-lipoxygenase protein in pineal glands was high in the dark and lowest around 16 o'clock. A half life of the enzyme protein was estimated to be approximately 2.8 h in organ culture of rat pineal glands. Northern blot analysis also revealed a higher 12-lipoxygenase mRNA level in pineal glands obtained in the dark than those obtained in the light. Thus, the 12-lipoxygenase of rat pineal glands shows a diurnal fluctuation that is regulated at the transcription level, and may play a certain role in the regulation of neuroendocrine processes of this gland.

When a crude extract of rat pineal glands (the 1000 x g supernatant of a homogenate) was incubated with arachidonic acid, 12-hydroxy-5,8,10,14-eicosatetraenoic acid was found as a major product. The 12-lipoxygenase of rat pineal gland also reacted with linoleic and alpha-linolenic acids at 35% and 101% the rate of arachidonate 12-oxygenation, respectively. Upon Western blot analysis using polyclonal antibody against porcine leukocyte 12-lipoxygenase, the cytosol fraction of rat pineal gland showed a positive band with a molecular weight of approx. 74 kDa. A full-length cDNA for this enzyme was cloned from a cDNA library of rat pineal gland and the identity of the 12-lipoxygenase cDNA was confirmed by its expression in E. coli. The amino acid sequence of the enzyme was deduced from the nucleotide sequence of the cDNA, encoding 663 amino acids with a calculated molecular weight of 75,305. The enzyme showed 72% identity of amino acid sequence with porcine leukocyte 12-lipoxygenase and 73% with bovine tracheal 12-lipoxygenase, but only 59% with human platelet 12-lipoxygenase. Taken together, the high reactivity with C-18 fatty acids, the immunoreactivity and the amino acid homology data indicate that the rat pineal 12-lipoxygenase is more closely related to leukocyte 12-lipoxygenase than to platelet 12-lipoxygenase. Upon RNA blot analysis, by far the highest content of 12-lipoxygenase mRNA was observed in the pineal gland and negligible amounts of mRNA were detected in other parts of the brain. The predominant presence of 12-lipoxygenase mRNA in pineal gland was confirmed by in situ hybridization of rat brain. Significant amounts of 12-lipoxygenase mRNA were also detected in rat spleen, aorta, lung and leukocytes.