ABSTRACT
Empyema is typically treated using pleural space drainage and systemic treatment with antimicrobials, and specific antimicrobial agents in the case of methicillin-resistant Staphylococcus aureus (MRSA) infections. A 57-year-old man underwent segmental resection of the left lung owing to multiple lung metastases and developed MRSA-related empyema postoperatively. Although the patient received chest drainage and linezolid, the inflammation caused by the infection persisted. Consequently, linezolid was replaced by daptomycin, and his empyema was accordingly resolved. Our findings indicate that daptomycin could be an effective treatment for postoperative MRSA-related empyema.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Daptomycin/therapeutic use , Empyema/drug therapy , Methicillin-Resistant Staphylococcus aureus , Postoperative Complications/drug therapy , Staphylococcal Infections/drug therapy , Humans , Lung Neoplasms/secondary , Lung Neoplasms/surgery , Male , Middle AgedABSTRACT
Background Chemotherapy-induced febrile neutropenia is a common and potentially lethal side effect; therefore, predicting febrile neutropenia development is important. Objective This study examined the risk factors for febrile neutropenia development according to breast cancer subtype among Japanese patients receiving chemotherapy. Methods This single-center retrospective study evaluated 60 outpatients who received chemotherapy for breast cancer (epirubicin plus cyclophosphamide or docetaxel plus cyclophosphamide). Their characteristics were evaluated to identify factors associated with febrile neutropenia development. Results Thirty-three patients developed febrile neutropenia and 27 patients did not. The risk of developing febrile neutropenia was significantly associated with estrogen receptor negativity (p < 0.05). Logistic regression analysis further confirmed that estrogen receptor negativity was an independent risk factor for febrile neutropenia development (odds ratio: 4.35, 95% confidence interval: 1.05-18.0). Moreover, the highest rate of febrile neutropenia was observed in patients with hormone receptor (estrogen and/or progesterone receptor)-negative/human epidermal growth factor receptor 2-positive breast cancer. Conclusion In addition to the known risk factors for febrile neutropenia, our findings revealed that the risk of developing chemotherapy-induced febrile neutropenia is associated with the hormone receptor-negative/human epidermal growth factor receptor 2-positive subtype in Japanese patients with breast cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/drug therapy , Breast Neoplasms/epidemiology , Chemotherapy-Induced Febrile Neutropenia/epidemiology , Adult , Breast Neoplasms/classification , Chemotherapy-Induced Febrile Neutropenia/diagnosis , Female , Humans , Japan/epidemiology , Middle AgedABSTRACT
Regenerative medicine using umbilical cord blood (UCB) cells shows promise for the treatment of cerebral palsy. Although the efficacy of this therapy has been seen in the clinic, the mechanisms by which UCB cells interact and aid in the improvement of symptoms are not clear. We explored the chemokine expression profile in damaged brain tissue in the neonatal mouse ischemia-reperfusion (IR) brain injury model that was infused with human UCB (hUCB) cells. IR brain injury was induced in 9-day-old NOD/SCID mice. hUCB cells were administered 3 weeks post brain injury. Chemokine expression profiles in the brain extract were determined at various time points. Inflammatory chemokines such as CCL1, CCL17, and CXCL12 were transiently upregulated by 24 hours post brain injury. Upregulation of other chemokines, including CCL5, CCL9, and CXCL1 were prolonged up to 3 weeks post brain injury, but most chemokines dissipated over time. There were marked increases in levels of CCL2, CCL12, CCL20, and CX3CL1 in response to hUCB cell treatment, which might be related to the new recruitment and differentiation of neural stem cells, leading to the induction of tissue regeneration. We propose that the chemokine expression profile in the brain shifted from responding to tissue damage to inducing tissue regeneration. hUCB cell administration further enhanced the production of chemokines, and chemokine networks may play an active role in tissue regeneration in neonatal hypoxic-ischemic brain injury.
Subject(s)
Brain Injuries/etiology , Brain Injuries/pathology , Chemokines/genetics , Cord Blood Stem Cell Transplantation , Fetal Blood/cytology , Reperfusion Injury/etiology , Reperfusion Injury/pathology , Animals , Biomarkers , Brain Injuries/therapy , Chemokines/metabolism , Cord Blood Stem Cell Transplantation/methods , Cytokines/metabolism , Disease Models, Animal , Humans , Mice , Mice, Inbred NOD , Mice, SCID , Reperfusion Injury/therapyABSTRACT
In diabetic patients, skeletal muscle atrophy occurs due to increased oxidative stress and inflammation. Skeletal muscle atrophy reduces the QOL of patients and worsens life prognosis. Therefore, development of preventive therapy for muscle atrophy in hyperglycemic state is eagerly awaited. Juzentaihoto is a medicinal herb that has a function to supplement physical strength, and it is expected to prevent muscle atrophy. To determine the preventive effect of juzentaihoto on muscle atrophy in hyperglycemic state, streptozotocin (STZ) was administered to induce diabetes in mice and the preventive effect of juzentaihoto was evaluated. Mice that received juzentaihoto extract (JTT) showed that the decrease in muscle fiber cross-sectional area in the gastrocnemius muscle was reversed. Additionally, the expression level of tumor necrosis factor α (TNF-α), an inflammatory cytokine, in serum decreased, and that of ubiquitin ligase (atrogin-1, muscle RING-finger protein-1) mRNA in skeletal muscle decreased. An anti-inflammatory cytokine interleukin-10 showed increased levels in the serum and increased levels in spleen cell culture supernatant collected from mice that received JTT. JTT had no effect on the blood glucose level. These results suggest that prophylactic administration of JTT to STZ-induced diabetic mice affects immune cells such as in spleen, causing an anti-inflammatory effect and inhibiting excessive activation of the ubiquitin-proteasome system, to reverse muscle atrophy.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Drugs, Chinese Herbal/therapeutic use , Muscular Atrophy/drug therapy , Animals , Anti-Inflammatory Agents/pharmacology , Blood Glucose/analysis , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/pathology , Drugs, Chinese Herbal/pharmacology , Interleukin-10/blood , Male , Mice, Inbred ICR , Muscle Fibers, Skeletal/drug effects , Muscle Fibers, Skeletal/pathology , Muscle Proteins/genetics , Muscular Atrophy/blood , Muscular Atrophy/genetics , Muscular Atrophy/pathology , SKP Cullin F-Box Protein Ligases/genetics , Tripartite Motif Proteins/genetics , Tumor Necrosis Factor-alpha/blood , Ubiquitin-Protein Ligases/geneticsABSTRACT
A decrease in skeletal muscle mass and motor function occurs in diabetic patients. In type 1 diabetic patients, in particular, fast-type fiber-dominated muscle atrophy occurs due to increased oxidative stress and inflammation. Juzentaihoto is a herbal medicine that has been found to be effective in reducing oxidative stress. In this study, juzentaihoto hot water extract (JTT) was administered prophylactically to mice with diabetic oxidative stress, which was induced by an injection of streptozotocin, and the effects on skeletal muscle mass, motor function, and antioxidant activity were evaluated. In mice that were administered JTT, skeletal muscle atrophy and loss of motor function were suppressed. Additionally, the administration of JTT increased the mRNA expression level of Sirt1 and the activity of superoxide dismutase in the gastrocnemius. In addition to skeletal muscle atrophy, atrophy of the liver, spleen and thymus gland, and kidney hypertrophy were also suppressed. Furthermore, in order to evaluate the antioxidant activity of 10 constituent crude drugs that comprise juzentaihoto, Sirt1 transcriptional activity in C2C12 cells was evaluated. The Sirt1 transcriptional activity was increased by Cinnamomi Cortex, Astragali Radix, and Glycyrrhizae Radix extracts. These three constituent crude drugs play an important function in the antioxidant action of juzentaihoto, suggesting that juzentaihoto can prevent muscle atrophy by decreasing oxidative stress.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Drugs, Chinese Herbal/therapeutic use , Muscular Atrophy/drug therapy , Oxidative Stress/drug effects , Phytotherapy/methods , Plant Extracts/therapeutic use , Streptozocin/adverse effects , Water/chemistry , Animals , Diabetes Mellitus, Experimental/chemically induced , Drugs, Chinese Herbal/pharmacology , Hot Temperature , Male , Mice , Plant Extracts/pharmacologyABSTRACT
Dyslipidaemia is a risk factor for arteriosclerosis. Recent studies have shown that dyslipidaemia is effectively prevented by various polyphenols. In this clinical study (UMIN trial: 000024028), we evaluated the beneficial effects of polyphenols contained in Goishi tea on blood lipid profiles. Seventy-seven subjects with LDL cholesterol (CHO) â§120 mg/mL were randomly divided into two groups for 12 weeks of polyphenol intake as follows: the Goishi tea group for daily consumption of Goishi tea containing 122 mg of polyphenols and the placebo group for the corresponding consumption of a placebo drink containing 12.2 mg of polyphenols. Intake of Goishi tea polyphenols tended to increase HDL CHO and suppress the elevation of triglycerides. These effects were particularly notable among the subjects with a body mass index <25 kg/m2. These findings suggest that Goishi tea polyphenols may suppress arteriosclerosis and reduce cardiovascular event risk by improving blood lipid profiles and thereby preventing dyslipidaemia.
Subject(s)
Cholesterol, HDL/blood , Cholesterol, LDL/blood , Hyperlipidemias/drug therapy , Polyphenols/pharmacology , Tea/chemistry , Triglycerides/blood , Adult , Blood Pressure , Double-Blind Method , Female , Humans , Male , Middle Aged , Polyphenols/chemistry , Young AdultABSTRACT
Minerals are essential for life, as they are a vital part of protein constituents, enzyme cofactors, and other components in living organisms. Deep sea water is characterized by its cleanliness and stable low temperature, and its possible health- and medical benefits are being studied. However, no study has yet evaluated the physical properties of the numerous commercially available deep sea water products, which have varying water sources and production methods. We analyzed these products' mineral content and investigated their effect on living organism, focusing on immune functions, and investigated the relation between physiological immunoactivities and mineral intake. We qualitatively analyzed the mineral compositions of the deep sea water drinks and evaluated the drinks' physical properties using principal component analysis, a type of multivariate analysis, of their mineral content. We create an iron and copper-deficient rat model and administered deep sea water drinks for 8 weeks. We then measured their fecal immunoglobulin A (IgA) to evaluate immune function. Principal component analysis suggested that physical properties of deep sea water drinks could be determined by their sources. Administration of deep sea water drinks increased fecal IgA, thus tending to stimulate immune function, but the extent of this effect varied by drink. Of the minerals contained in deep sea water, iron showed positive correlations with the fecal IgA. The principal component analysis used in this study is suitable for evaluating deep sea water containing many minerals, and our results form a useful basis for comparative evaluations of deep sea water's bioactivity.
Subject(s)
Beverages , Immunoglobulin A/immunology , Intestines/immunology , Minerals/pharmacology , Seawater , Animals , Beverages/analysis , Copper , Diet , Feces/chemistry , Iron , Male , Minerals/analysis , Rats, Wistar , Seawater/analysisABSTRACT
We previously prepared and pharmaceutically evaluated ginger orally disintegrating (OD) tablets, optimized the base formulation, and carried out a clinical trial in healthy adults in their 20 s and 50s to measure their effect on salivary substance P (SP) level and improved swallowing function. In this study, we conducted clinical trials using the ginger OD tablets in older people to clinically evaluate the improvements in swallowing function resulting from the functional components of the tablet. The ginger OD tablets were prepared by mixing the excipients with the same amount of mannitol and sucrose to a concentration of 1% ginger. Eighteen healthy older adult volunteers aged 63 to 90 were included in the swallowing function test. Saliva was collected before and 15 min after administration of the placebo and ginger OD tablets. Swallowing endoscopy was performed by an otolaryngologist before administration and 15 min after administration of the ginger OD tablets. A scoring method was used to evaluate the endoscopic swallowing. Fifteen minutes after taking the ginger OD tablets, the salivary SP amount was significantly higher than prior to ingestion or after taking the placebo (p<0.05). Among 10 subjects, one scored 1-3 using the four evaluation criteria. Overall, no aspiration occurred and a significant improvement in the swallowing function score was observed (p<0.05) after taking the ginger OD tablets. Our findings showed that the ginger OD tablets increased the salivary SP amount and improved swallowing function in older people with appreciably reduced swallowing function.
Subject(s)
Deglutition/drug effects , Plant Preparations/administration & dosage , Zingiber officinale , Administration, Oral , Aged , Aged, 80 and over , Catechols/administration & dosage , Catechols/analysis , Catechols/pharmacology , Excipients/chemistry , Fatty Alcohols/administration & dosage , Fatty Alcohols/analysis , Fatty Alcohols/pharmacology , Female , Humans , Male , Mannitol/chemistry , Middle Aged , Plant Preparations/chemistry , Plant Preparations/pharmacology , Powders , Saliva/metabolism , Solubility , Substance P/metabolism , Sucrose/chemistry , TRPV Cation Channels/agonists , TabletsABSTRACT
The introduction of generic drugs is promoted from the perspective of medical economics. In this context, we need to understand not only the bioequivalence of generic drugs specified in "the Guidelines for Bioequivalence Studies of Generic Products", but also formulation properties to consider their effect on pharmacological therapy. We evaluated the pharmaceutical characteristics of rebamipide formulations, a brand-name drug and two generic drugs, and their clinical functionality by using rat models of gastric mucosal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs). Pharmaceutical evaluation showed significant differences in hardness. The inter-lot variation was small in all rebamipide formulations. In the clinical functionality study, biochemistry test values 7 d after the administration of rebamipide showed no differences among formulations. Higher levels of mucosal fluid secretion and antioxidative enzymes were observed in the groups administered rebamipide than in the control group. The levels of lipid peroxide were lower in the groups administered rebamipide than the control group. Multivariate analysis showed slight divergence between the brand-name and generic drugs. In future, it will be necessary to select generic drugs after careful consideration of bioequivalence, clinical functionality, and therapeutic equivalence by reviewing scientific evidence such as indication and formulation design, not to mention stable provision.
Subject(s)
Alanine/analogs & derivatives , Anti-Ulcer Agents/pharmacokinetics , Anti-Ulcer Agents/therapeutic use , Drugs, Generic/pharmacology , Drugs, Generic/therapeutic use , Quinolones/pharmacokinetics , Quinolones/therapeutic use , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Alanine/pharmacokinetics , Alanine/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Disease Models, Animal , Drug Compounding , Drugs, Generic/pharmacokinetics , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Indomethacin/adverse effects , Lipid Peroxides/metabolism , Male , Rats, Wistar , Stomach Ulcer/metabolism , Therapeutic EquivalencyABSTRACT
Bangle (Zingiber purpureum) is a tropical ginger that is used as a spice in Southeast Asia. Phenylbutenoid dimers isolated from Bangle have exhibited neurotrophic effects in primary cultured rat cortical neurons and PC12 cells. Furthermore, chronic treatment with phenylbutenoid dimers enhances hippocampal neurogenesis in olfactory bulbectomized mice. In this study, we investigated the effects of Bangle extract on behavior and hippocampal neurogenesis in vivo. SAMP8 mice, which are an established model for accelerated aging, with age-related learning and memory impairments, were given a Bangle-containing diet for 1 month, and subsequent behavioral tests and immunohistochemistry for Ki67, a proliferating cell marker, were performed. We found that the Bangle-containing diet improved spatial learning and memory deficits in the Morris water maze and significantly increased the numbers of Ki67-positive cells in the dentate gyrus of the SAMP8 mice. In addition, the Bangle extract exhibited a neurotrophin-like activity as indicated by the induction of neurite sprouting in PC12 cells. Our results suggest that Bangle is beneficial for the prevention of age-related progression of cognitive impairment.
Subject(s)
Aging/drug effects , Memory Disorders/drug therapy , Neurogenesis/drug effects , Neurons/drug effects , Spatial Learning/drug effects , Zingiberaceae/chemistry , Aging/psychology , Animals , Dentate Gyrus/drug effects , Dentate Gyrus/physiopathology , Disease Models, Animal , Humans , Male , Memory/drug effects , Memory Disorders/physiopathology , Memory Disorders/psychology , Mice , Mice, Transgenic , Neurons/cytology , PC12 Cells , RatsABSTRACT
Disrupted-in-schizophrenia 1 (DISC1) is a susceptibility gene for major psychiatric disorders, including schizophrenia. DISC1 has been implicated in neurodevelopment in relation to scaffolding signal complexes. Here we used proteomic analysis to screen for DISC1 interactors and identified several RNA-binding proteins, such as hematopoietic zinc finger (HZF), that act as components of RNA-transporting granules. HZF participates in the mRNA localization of inositol-1,4,5-trisphosphate receptor type 1 (ITPR1), which plays a key role in synaptic plasticity. DISC1 colocalizes with HZF and ITPR1 mRNA in hippocampal dendrites and directly associates with neuronal mRNAs, including ITPR1 mRNA. The binding potential of DISC1 for ITPR1 mRNA is facilitated by HZF. Studies of Disc1-knockout mice have revealed that DISC1 regulates the dendritic transport of Itpr1 mRNA by directly interacting with its mRNA. The DISC1-mediated mRNA regulation is involved in synaptic plasticity. We show that DISC1 binds ITPR1 mRNA with HZF, thereby regulating its dendritic transport for synaptic plasticity.
Subject(s)
Hippocampus/metabolism , Inositol 1,4,5-Trisphosphate Receptors/genetics , Nerve Tissue Proteins/physiology , Neuronal Plasticity/physiology , Proteins/physiology , RNA, Messenger/metabolism , RNA-Binding Proteins/physiology , 3' Untranslated Regions/genetics , Animals , Biological Transport , Cytoplasmic Granules/metabolism , Dendrites/metabolism , Dendrites/ultrastructure , Hippocampus/cytology , Humans , Mice , Mice, Inbred C57BL , Nerve Tissue Proteins/deficiency , Nerve Tissue Proteins/genetics , Neuronal Plasticity/genetics , Protein Binding , Protein Interaction Mapping , RNA Interference , RNA-Binding Proteins/genetics , Recombinant Fusion Proteins/metabolismABSTRACT
The small GTP-binding protein Rho plays a crucial role in a wide variety of cellular functions through various effector proteins. Rho-kinase is a key effector protein of Rho, which is composed of two isoforms, ROCK1 and ROCK2. To clarify the site of action of ROCK1 and ROCK2, we performed immunofluorescence and immunoelectron microscopic analyses using isoform-specific antibodies in mouse tissues. In the large and small intestines, ROCK1 immunoreactivity was predominantly identified in epithelial cells, and ROCK2 immunoreactivity was negligible. In these epithelial cells, ROCK1 immunoreactivity was distributed on plasma membranes, while ROCK1 immunogold signals were localized at cell-cell contacts and cell adhesion sites, especially at the adherens junctions at the ultrastructural level. In the bladder epithelium, however, ROCK1 and ROCK2 signals were identified at intermediate filaments, and ROCK2 signals were also observed in nuclei. In the three types of muscular cells-smooth, cardiac, and skeletal muscle cells-ROCK1 and ROCK2 also showed differential distribution. ROCK1 signals were localized at actin filaments, plasma membranes, and vesicles near plasma membranes in smooth muscle cells; at the lysosomes in skeletal muscle cells; and were undetectable in cardiac muscle cells. ROCK2 signals were localized at actin filaments and centrosomes in smooth muscle cells, at intercalated discs in cardiac muscle cells, and at Z-discs and sarcoplasmic reticulum in skeletal muscle cells. In the brain, ROCK1 immunoreactivity was distributed in glia, whereas ROCK2 immunoreactivity was observed in neurons. These results indicate that the two isoforms of Rho-kinase distribute differentially to accomplish their specific functions.
Subject(s)
Brain/enzymology , Epithelium/enzymology , Muscles/enzymology , rho-Associated Kinases/metabolism , Animals , Brain/cytology , HeLa Cells , Humans , Intracellular Space/enzymology , Mice , Mice, Inbred C57BL , Muscles/cytology , Organ Specificity , Protein TransportABSTRACT
Disrupted-In-Schizophrenia 1 (DISC1) is a promising candidate gene for susceptibility to psychiatric disorders, including schizophrenia. DISC1 appears to be involved in neurogenesis, neuronal migration, axon/dendrite formation and synapse formation; during these processes, DISC1 acts as a scaffold protein by interacting with various partners. However, the lack of Disc1 knockout mice and a well-characterized antibody to DISC1 has made it difficult to determine the exact role of DISC1 in vivo. In this study, we generated mice lacking exons 2 and 3 of the Disc1 gene and prepared specific antibodies to the N- and C-termini of DISC1. The Disc1 mutant mice are viable and fertile, and no gross phenotypes, such as disorganization of the brain's cytoarchitecture, were observed. Western blot analysis revealed that the DISC1-specific antibodies recognize a protein with an apparent molecular mass of ~100 kDa in brain extracts from wild-type mice but not in brain extracts from DISC1 mutant mice. Immunochemical studies demonstrated that DISC1 is mainly localized to the vicinity of the Golgi apparatus in hippocampal neurons and astrocytes. A deficiency of full-length Disc1 induced a threshold shift in the induction of long-term potentiation in the dentate gyrus. The Disc1 mutant mice displayed abnormal emotional behavior as assessed by the elevated plus-maze and cliff-avoidance tests, thereby suggesting that a deficiency of full-length DISC1 may result in lower anxiety and/or higher impulsivity. Based on these results, we suggest that full-length Disc1-deficient mice and DISC1-specific antibodies are powerful tools for dissecting the pathophysiological functions of DISC1.