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1.
Surg Case Rep ; 7(1): 102, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33891220

RESUMO

BACKGROUND: True primary enterolithiasis is an uncommon condition, and nontraumatic perforation of the small intestine (NTPSI) is also an unusual entity. Therefore, NTPSI due to true primary enteroliths is an exceptionally rare complication. Moreover, enterolithiasis and radiation enteritis are also unique combinations. Herein, we present an exceedingly rare case of NTPSI induced by multiple true primary enteroliths associated with radiation enteritis. CASE PRESENTATION: A 92-year-old woman with acute abdominal pain was transferred to our hospital because a computed tomography (CT) scan performed by her family doctor revealed free air and fluid collection within her abdomen. Our initial diagnosis was upper gastrointestinal perforation, and we selected nonoperative management (NOM) with adnominal drainage. Although her general condition was stable, jejunal juice was drained continuously. Given that the CT performed 10 days after onset demonstrated perforation of the small intestine and adjacent concretion, we performed an emergency partial resection of the small intestine and jejunostomy. The resected bowel was 1 m in length and had many strictures that contained multiple enteroliths in their proximal lumens. The patient's postoperative course was uneventful. The enteroliths were composed of deoxycholic acid (DCA). She was diagnosed with peritonitis due to NTPSI derived from multiple true primary enteroliths associated with radiation enteritis, as she had previously undergone hysterectomy and subsequent internal radiation therapy. CONCLUSIONS: Clinicians should consider the rare entity of true primary enteroliths associated with radiation enteritis in NTPSI cases with unknown etiologies.

2.
J Biol Chem ; 295(21): 7274-7288, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32284328

RESUMO

Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that critically supports the physicochemical and mechanical properties of the skin. Here, we demonstrate that mycosporine-like amino acids (MAAs), which typically function as UV-absorbing compounds, can stimulate HA secretion from normal human fibroblasts. MAA-stimulated HA secretion was associated with significantly increased and decreased levels of mRNAs encoding HA synthase 2 (HAS2) and the HA-binding protein involved in HA depolymerization (designated HYBID), respectively. Using immunoblotting, we found that MAAs at 10 and at 25 µg/ml stimulate the phosphorylation of the mitogen-activated protein kinase (MAPK) p38, extracellular signal-regulated kinase (ERK)/c-Jun, and mitogen- and stress-activated protein kinase 1 (MSK1) (at Thr-581, Ser-360, and Ser-376, respectively) and activation of cAMP-responsive element-binding protein (CREB) and activating transcription factor 2 (ATF2), but not phosphorylation of JUN N-terminal kinase (JNK) or NF-κB (at Ser-276 or Ser-536, respectively), and increased c-Fos protein levels. Moreover, a p38-specific inhibitor, but not inhibitors of MAPK/ERK kinase (MEK), JNK, or NF-κB, significantly abrogated the increased expression of HAS2 mRNA, accompanied by significantly decreased MAA-stimulated HA secretion. These results suggested that the p38-MSK1-CREB-c-Fos-transcription factor AP-1 (AP-1) or the p38-ATF2 signaling cascade is responsible for the MAA-induced stimulation of HAS2 gene expression. Of note, siRNA-mediated ATF2 silencing failed to abrogate MAA-stimulated HAS2 expression, and c-Fos silencing abolished the increased expression of HAS2 mRNA. Our findings suggest that MAAs stimulate HA secretion by up-regulating HAS2 mRNA levels through activation of an intracellular signaling cascade consisting of p38, MSK1, CREB, c-Fos, and AP-1.


Assuntos
Aminoácidos/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hialuronan Sintases/biossíntese , Ácido Hialurônico/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Células Cultivadas , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Humanos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Fator de Transcrição AP-1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
3.
J Comput Chem ; 39(27): 2333-2344, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30238477

RESUMO

The Relativistic And Quantum Electronic Theory (RAQET) program is a new software package, which is designed for large-scale two-component relativistic quantum chemical (QC) calculations. The package includes several efficient schemes and algorithms for calculations involving large molecules which contain heavy elements in accurate relativistic formalisms. These calculations can be carried out in terms of the two-component relativistic Hamiltonian, wavefunction theory, density functional theory, core potential scheme, and evaluation of electron repulsion integrals. Furthermore, several techniques, which have frequently been used in non-relativistic QC calculations, have been customized for relativistic calculations. This article introduces the brief theories and capabilities of RAQET with several calculation examples. © 2018 Wiley Periodicals, Inc.

4.
J Comput Chem ; 38(29): 2520-2527, 2017 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-28795766

RESUMO

We have implemented a linear-scaling divide-and-conquer (DC)-based higher-order coupled-cluster (CC) and Møller-Plesset perturbation theories (MPPT) as well as their combinations automatically by means of the tensor contraction engine, which is a computerized symbolic algebra system. The DC-based energy expressions of the standard CC and MPPT methods and the CC methods augmented with a perturbation correction were proposed for up to high excitation orders [e.g., CCSDTQ, MP4, and CCSD(2)TQ ]. The numerical assessment for hydrogen halide chains, polyene chains, and first coordination sphere (C1) model of photoactive yellow protein has revealed that the DC-based correlation methods provide reliable correlation energies with significantly less computational cost than that of the conventional implementations. © 2017 Wiley Periodicals, Inc.

5.
J Cell Sci ; 130(15): 2631-2643, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28676501

RESUMO

Reactive oxygen species (ROS), originally characterized based on their harmful effects on cells or organisms, are now recognized as important signal molecules regulating various biological processes. In particular, low levels of ROS released from mitochondria extend lifespan. Here, we identified a novel mechanism of generating appropriate levels of ROS at the plasma membrane through a peroxidase and dual oxidase (DUOX) system, which could extend lifespan in Caenorhabditis elegans A redox co-factor, pyrroloquinoline quinone (PQQ), activates the C. elegans DUOX protein BLI-3 to produce the ROS H2O2 at the plasma membrane, which is subsequently degraded by peroxidase (MLT-7), eventually ensuring adequate levels of ROS. These ROS signals are transduced mainly by the oxidative stress transcriptional factors SKN-1 (Nrf2 or NFE2L2 in mammals) and JUN-1, and partially by DAF-16 (a FOXO protein homolog). Cell biology experiments demonstrated a similarity between the mechanisms of PQQ-induced activation of human DUOX1 and DUOX2 and that of C. elegans BLI-3, suggesting that DUOXs are potential targets of intervention for lifespan extension. We propose that low levels of ROS, fine-tuned by the peroxidase and dual oxidase system at the plasma membrane, act as second messengers to extend lifespan by the effect of hormesis.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Oxidases Duais/metabolismo , Longevidade/fisiologia , Oxirredutases/metabolismo , Cofator PQQ/metabolismo , Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Oxidases Duais/genética , Oxirredutases/genética , Cofator PQQ/genética , Peroxidase/genética
6.
Adv Exp Med Biol ; 923: 215-222, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27526146

RESUMO

Pyrroloquinoline quinone (PQQ) is a quinone compound originally identified in methanol-utilizing bacteria and is a cofactor for redox enzymes. At the Meeting of the International Society on Oxygen Transport to Tissue (ISOTT) 2014, we reported that PQQ disodium salt (BioPQQ™) improved cognitive function in humans, as assessed by the Stroop test. However, the physiological mechanism of PQQ remains unclear. In the present study, we measured regional cerebral blood flow (rCBF) and oxygen metabolism in prefrontal cortex (PFC), before and after administration of PQQ, using time-resolved near-infrared spectroscopy (tNIRS). A total of 20 healthy subjects between 50 and 70 years of age were administered BioPQQ™ (20 mg) or placebo orally once daily for 12 weeks. Hemoglobin (Hb) concentration and absolute tissue oxygen saturation (SO2) in the bilateral PFC were evaluated under resting conditions using tNIRS. We found that baseline concentrations of hemoglobin and total hemoglobin in the right PFC significantly increased after administration of PQQ (p < 0.05). In addition, decreases in SO2 level in the PFC were more pronounced in the PQQ group than in the placebo group (p < 0.05). These results suggest that PQQ causes increased activity in the right PFC associated with increases in rCBF and oxygen metabolism, resulting in enhanced cognitive function.


Assuntos
Antioxidantes/administração & dosagem , Circulação Cerebrovascular/efeitos dos fármacos , Suplementos Nutricionais , Consumo de Oxigênio/efeitos dos fármacos , Oxigênio/sangue , Cofator PQQ/administração & dosagem , Córtex Pré-Frontal/irrigação sanguínea , Córtex Pré-Frontal/efeitos dos fármacos , Administração Oral , Idoso , Biomarcadores/sangue , Velocidade do Fluxo Sanguíneo , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Oximetria/métodos , Oxiemoglobinas/metabolismo , Córtex Pré-Frontal/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho , Tóquio
7.
Adv Exp Med Biol ; 876: 319-325, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26782228

RESUMO

Pyrroloquinoline quinone (PQQ) is a quinone compound first identified in 1979. It has been reported that rats fed a PQQ-supplemented diet showed better learning ability than controls, suggesting that PQQ may be useful for improving memory in humans. In the present study, a randomized, placebo-controlled, double-blinded study to examine the effect of PQQ disodium salt (BioPQQ™) on cognitive functions was conducted with 41 elderly healthy subjects. Subjects were orally given 20 mg of BioPQQ™ per day or placebo, for 12 weeks. For cognitive functions, selective attention by the Stroop and reverse Stroop test, and visual-spatial cognitive function by the laptop tablet Touch M, were evaluated. In the Stroop test, the change of Stroop interference ratios (SIs) for the PQQ group was significantly smaller than for the placebo group. In the Touch M test, the stratification analyses dividing each group into two groups showed that only in the lower group of the PQQ group (initial score<70), did the score significantly increase. Measurements of physiological parameters indicated no abnormal blood or urinary adverse events, nor adverse internal or physical examination findings at any point in the study. The preliminary experiment using near-infrared spectrometry (NIRS) suggests that cerebral blood flow in the prefrontal cortex was increased by the administration of PQQ. The results suggest that PQQ can prevent reduction of brain function in aged persons, especially in attention and working memory.


Assuntos
Antioxidantes/farmacologia , Cognição/efeitos dos fármacos , Cofator PQQ/farmacologia , Idoso , Circulação Cerebrovascular/efeitos dos fármacos , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espectroscopia de Luz Próxima ao Infravermelho
8.
Biosci Biotechnol Biochem ; 80(1): 13-22, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26168402

RESUMO

Pyrroloquinoline quinone (PQQ), an aromatic tricyclic o-quinone, was identified initially as a redox cofactor for bacterial dehydrogenases. Although PQQ is not biosynthesized in mammals, trace amounts of PQQ have been found in human and rat tissues because of its wide distribution in dietary sources. Importantly, nutritional studies in rodents have revealed that PQQ deficiency exhibits diverse systemic responses, including growth impairment, immune dysfunction, and abnormal reproductive performance. Although PQQ is not currently classified as a vitamin, PQQ has been implicated as an important nutrient in mammals. In recent years, PQQ has been receiving much attention owing to its physiological importance and pharmacological effects. In this article, we review the potential health benefits of PQQ with a focus on its growth-promoting activity, anti-diabetic effect, anti-oxidative action, and neuroprotective function. Additionally, we provide an update of its basic pharmacokinetics and safety information in oral ingestion.


Assuntos
Antioxidantes/farmacologia , Suplementos Nutricionais , Hipoglicemiantes/farmacologia , Memória/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Cofator PQQ/farmacologia , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacocinética , Regulação da Expressão Gênica , Glucose/metabolismo , Humanos , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacocinética , Insulina/genética , Insulina/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/fisiologia , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacocinética , Oxirredução , Cofator PQQ/metabolismo , Cofator PQQ/farmacocinética , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Ratos , Receptor de Insulina/genética , Receptor de Insulina/metabolismo
9.
Biosci Biotechnol Biochem ; 80(1): 178-87, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26264520

RESUMO

Measurements of the reaction of sodium salt of pyrroloquinoline quinone (PQQNa2) with vitamin C (Vit C) were performed in phosphate-buffered solution (pH 7.4) at 25 °C under nitrogen atmosphere, using UV-vis spectrophotometry. The absorption spectrum of PQQNa2 decreased in intensity due to the reaction with Vit C and was changed to that of pyrroloquinoline quinol (PQQH2, a reduced form of PQQ). One molecule of PQQ was reduced by two molecules of Vit C producing a molecule of PQQH2 in the buffer solution. PQQH2, thus produced, was recycled to PQQ due to air oxidation. PQQ and Vit C coexist in many biological systems, such as vegetables, fruits, as well as in human tissues. The results obtained suggest that PQQ is reduced by Vit C and functions as an antioxidant in biological systems, because it has been reported that PQQH2 shows very high free-radical scavenging and singlet-oxygen quenching activities in buffer solutions.


Assuntos
Antioxidantes/química , Ácido Ascórbico/química , Hidroquinonas/química , Cofator PQQ/química , Ar , Soluções Tampão , Concentração de Íons de Hidrogênio , Oxirredução , Sais , Soluções , Espectrofotometria
10.
J Nutr Sci Vitaminol (Tokyo) ; 61(3): 233-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26226960

RESUMO

Pyrroloquinoline quinone (PQQ) is a water-soluble quinone compound that has a strong anti-oxidant capacity. A previous study in rats fed a PQQ-depleted diet showed that elevated levels of serum triglyceride (TG) decreased after PQQ supplementation. However, there is only one study reporting the effects of PQQ on serum lipid levels, such as those of TG and cholesterol, in humans. In this study, the effects of PQQ disodium salt (BioPQQ™) on serum TG and cholesterol levels in humans after 6 and 12 wk of treatment at an oral dosage of 20 mg/d were examined. This trial was conducted according to a randomized, placebo-controlled, double-blinded protocol. A total of 29 healthy Japanese adults, ranging from 40 to 57 y old, with normal to moderately high TG levels (110-300 mg/dL) as measured by a recent blood examination, were included in this study. In eleven volunteers out of 29, serum low-density lipoprotein cholesterol (LDL-chol) levels at baseline were high (≥140 mg/dL). After 12 wk, the mean serum TG levels had not changed; however, a marginally significant decrease in the mean LDL-chol (from 136.1 to 127.0 mg/dL) was observed in the PQQ group. In the stratification analysis of the high LDL-chol subgroup (baseline LDL-chol level ≥140 mg/dL), the mean LDL-chol levels decreased significantly from the baseline values in the PQQ group compared to the placebo group. Our study findings suggest that PQQ suppressed the LDL-chol level, which is an important finding, because a high level of this lipid is a risk factor for various lifestyle-related diseases.


Assuntos
LDL-Colesterol/efeitos dos fármacos , Cofator PQQ/farmacologia , Adulto , Povo Asiático , LDL-Colesterol/sangue , Dieta , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue
11.
J Nutr Sci Vitaminol (Tokyo) ; 61(3): 241-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26226961

RESUMO

Pyrroloquinoline quinone (PQQ) is a coenzyme involved in the redox-cycling system. The supplemental use of PQQ has been examined based on its properties as an antioxidant and redox modulator. Although an animal study on deficiency of PQQ suggested that PQQ contributes to skin conditions, its efficacy in humans has not been reported. The present study aimed to investigate the effects of orally administered PQQ on skin moisture, viscoelasticity, and transepidermal water loss (TEWL) both in dry skin mouse models and in healthy female subjects with a subjective symptom of dry skin. In our dry skin mouse model study, oral intake of PQQ (0.0089%, w/w, in the diet for 6 wk) significantly decreased the number of mast cells in the dermis and the number of CD3⁺ T-cells in the epidermis. In our human study, oral intake of PQQ (20 mg/d for 8 wk) significantly inhibited the increase in TEWL on the forearm. Finally, subject questionnaires showed positive impressions for the improvement of skin conditions. These results suggest that oral intake of PQQ improves skin conditions both in female subjects with dry skin and in mice with a compromised skin barrier function.


Assuntos
Cofator PQQ/farmacologia , Dermatopatias/tratamento farmacológico , Pele/efeitos dos fármacos , Perda Insensível de Água/efeitos dos fármacos , Administração Oral , Animais , Complexo CD3/metabolismo , Elasticidade/efeitos dos fármacos , Feminino , Voluntários Saudáveis , Humanos , Mastócitos/metabolismo , Camundongos , Camundongos Pelados , Oxirredução/efeitos dos fármacos , Cofator PQQ/administração & dosagem , Pele/fisiopatologia , Viscosidade/efeitos dos fármacos
12.
Regul Toxicol Pharmacol ; 70(1): 107-21, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24995591

RESUMO

The potential use of pyrroloquinoline quinone disodium salt (BioPQQ™), as a supplemental food ingredient, was evaluated in a range of oral toxicity studies in rats including an acute study, a 14-day preliminary and a 28-day repeated-dose study, and a 13-week subchronic study. The median lethal dose of BioPQQ™ was shown to be 1000-2000mg/kg body weight (bw) in male and 500-1000mg/kgbw in female rats. In the 14-day study, high doses of BioPQQ™ resulted in increases in relative kidney weights with associated histopathology in female rats only, while a follow-up 28-day study in female animals resulted in increases in urinary protein and crystals. These findings were reversible, and resolved during the recovery period. In the 13-week study, a number of clinical chemistry findings and histopathological changes were noted, which were deemed to be of no toxicological significance, as the levels were within the historical control range, were not dose-dependent, occurred at a similar frequency in control groups, or only occurred in the control group. Based on these findings, a no-observed-adverse-effect level of 100mg/kgbw/day was determined for BioPQQ™ in rats, the highest dose tested in the 13-week study.


Assuntos
Rim/efeitos dos fármacos , Cofator PQQ/toxicidade , Testes de Toxicidade Aguda/métodos , Testes de Toxicidade Subcrônica/métodos , Animais , Relação Dose-Resposta a Droga , Feminino , Rim/metabolismo , Dose Letal Mediana , Masculino , Nível de Efeito Adverso não Observado , Tamanho do Órgão/efeitos dos fármacos , Cofator PQQ/administração & dosagem , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
13.
J Agric Food Chem ; 61(46): 11048-60, 2013 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-24175624

RESUMO

Measurements of aroxyl radical (ArO•)-scavenging rate constants (ks AOH) of antioxidants (AOHs: pyrroloquinolinequinol (PQQH2), α-tocopherol (α-TocH), ubiquinol-10 (UQ10H2), epicatechin, epigallocatechin, epigallocatechin gallate, and caffeic acid) were performed in dimethyl sulfoxide (DMSO) solution, using stopped-flow spectrophotometry. The ks AOH values were measured not only for each AOH but also for the mixtures of two AOHs ((i) α-TocH and PQQH2 and (ii) α-TocH and UQ10H2). A notable synergistic effect that the ks AOH values increase 1.72, 2.42, and 2.50 times for α-TocH, PQQH2, and UQ10H2, respectively, was observed for the solutions including two kinds of AOHs. Measurements of the regeneration rates of α-tocopheroxyl radical (α-Toc•) to α-TocH by PQQH2 and UQ10H2 were performed in DMSO, using double-mixing stopped-flow spectrophotometry. Second-order rate constants (kr) obtained for PQQH2 and UQ10H2 were 1.08 × 105 and 3.57 × 104 M−1 s−1, respectively, indicating that the kr value of PQQH2 is 3.0 times larger than that of UQ10H2. It has been clarified that PQQH2 and UQ10H2 having two HO groups within a molecule may rapidly regenerate two molecules of α-Toc• to α-TocH. The result indicates that the prooxidant effect of α-Toc• is suppressed by the coexistence of PQQH2 or UQ10H2.


Assuntos
Dimetil Sulfóxido/química , Sequestradores de Radicais Livres/química , Cofator PQQ/química , alfa-Tocoferol/química , Cinética , Estrutura Molecular , Oxirredução
14.
Regul Toxicol Pharmacol ; 67(2): 189-97, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23891671

RESUMO

The genotoxic potential of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) was evaluated in a battery of genotoxicity tests. The results of the bacterial mutation assay (Ames test) were negative. Weak positive results were obtained in 2 separate in vitro chromosomal aberration test in Chinese hamster lung (CHL) fibroblasts. Upon testing in an in vitro chromosomal aberration test in human peripheral blood lymphocytes, no genotoxic activity of PQQ was noted. In the in vivo micronucleus assay in mice, PQQ at doses up to 2,000 mg/kg body weight demonstrated that no genotoxic effects are expressed in vivo in bone marrow erythrocytes. The weak responses in the in vitro test CHL cells were considered of little relevance under conditions of likely human exposure. PQQ disodium was concluded to have no genotoxic activity in vivo.


Assuntos
Cofator PQQ/toxicidade , Animais , Linhagem Celular , Células Cultivadas , Cricetulus , Feminino , Humanos , Pulmão/citologia , Linfócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Testes de Mutagenicidade , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/genética
15.
Biochem Biophys Res Commun ; 428(2): 315-20, 2012 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-23085227

RESUMO

Insulin resistance is a pathological hallmark of type 2 diabetes mellitus and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling by tyrosine dephosphorylation of insulin receptor, and increased activity and expression of PTP1B is implicated in the pathogenesis of insulin resistance. Therefore, inhibition of PTP1B is anticipated to improve insulin resistance in type 2 diabetic subjects. Pyrroloquinoline quinone (PQQ), a redox cofactor for bacterial dehydrogenases, inhibits PTP1B to oxidatively modify the catalytic cysteine through its redox cycling activity. Here, we report that PQQ induces the ligand-independent activation of insulin signaling by inhibiting cellular PTP1B and enhances glucose uptake through the translocation of glucose transporter 4 in mouse C2C12 myotubes. Furthermore, we demonstrated that oral administration of PQQ improved impaired glucose tolerance in type 2 diabetic KK-A(y) mice. Our results strongly suggest that PQQ can be useful in anti-diabetic treatment for type 2 diabetic subjects.


Assuntos
Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Tipo 2/enzimologia , Inibidores Enzimáticos/farmacologia , Intolerância à Glucose/enzimologia , Insulina/metabolismo , Cofator PQQ/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Camundongos , Camundongos Endogâmicos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/enzimologia , Fibras Musculares Esqueléticas/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Eur J Pharmacol ; 697(1-3): 53-8, 2012 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-23063836

RESUMO

Pyrroloquinoline quinone PQQ is a naturally occurring redox cofactor that acts as an essential nutrient, antioxidant, and redox modulator. PQQ has been demonstrated to oxidize the redox modulatory site of N-methyl-d-aspartic acid (NMDA) receptors. Such agents are known to be neuroprotective in experimental stroke models. However, there is not report about the therapeutic effect of PQQ on neuropathic pain. We tested the effects of oral administration of PQQ on neuropathic pain of rats with chronic constriction injury (CCI) of the sciatic nerve. The repeated oral administration of PQQ (20 and 40mg/kg, once a day for 4 weeks, from day 1 after the injury) attenuated both thermal and mechanical hyperalgesia, and also attenuated the muscle atrophy. The anti-hyperalgesic activity of PQQ was associated with a significant reduction of pro-inflammatory mediators such as tumor necrosis factor alpha (TNF-α) and lipid peroxide malondialdehyde (MDA) levels. In the present investigation, PQQ is shown to have analgesic effect which was found in the first time, probably through reducing the release of pro-inflammatory mediator and inhibiting oxidative stress.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Hiperalgesia/prevenção & controle , Cofator PQQ/farmacologia , Limiar da Dor/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Ciática/prevenção & controle , Administração Oral , Analgésicos/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Biomarcadores/metabolismo , Constrição , Modelos Animais de Doenças , Hiperalgesia/diagnóstico , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Mediadores da Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Atrofia Muscular/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Cofator PQQ/administração & dosagem , Medição da Dor , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Nervo Isquiático/metabolismo , Nervo Isquiático/fisiopatologia , Nervo Isquiático/cirurgia , Ciática/diagnóstico , Ciática/etiologia , Ciática/metabolismo , Ciática/fisiopatologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo
17.
Surg Endosc ; 26(10): 2981-7, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22955895

RESUMO

BACKGROUND: The number of cases of laparoscopic surgery has been increasing. Lymph node dissection has been standardized, and the enlarged view provided by laparoscopes allows for the procedure to be performed successfully entirely within the abdominal cavity, but many cases of reconstruction using the Billroth-I method are performed under direct vision through a small incision. In this study, by placing an anchor thread on a suture line on the lesser curvature of the stomach, we simplified the procedure for handsewn anastomosis and safely performed gastroduodenal anastomosis at low cost to obtain good results. METHODS: From January 2009 to December 2010, we performed handsewn gastroduodenal anastomosis in 18 cases. After performing lymph node dissection, the duodenum and the stomach were separated using an automatic stapling device. Anchor sutures were placed on the suture line of the lesser curvature of the stomach. First, the seromuscular layer of the stomach and the seromuscular layer of the duodenum were sutured by performing interrupted suturing using an extracorporeal knot-tying method. With the stomach and the duodenum in a fixed state, the anastomosis area was opened. The thread of the anchor suture was pulled toward the abdominal wall, and then all layers of the stomach and the duodenum at the posterior wall were continuously sutured. Similarly, for the anterior wall, all layers were continuously sutured from the lesser curvature toward the greater curvature. RESULTS: We performed this anastomotic procedure in 18 patients with early gastric carcinoma. The mean time required for the anastomosis was 64.6 ± 17.1 min, and the estimated blood loss was 53.1 ± 91 g. All operations were curative, and the mean number of retrieved lymph node was 27.1 ± 10.8. A nasogastric tube was removed on the first or second day. An upper gastrointestinal series performed on postoperative days 5-6 showed no anastomotic leakage and normal transit. Oral intake was started on days 6-7. Postoperative complications included one case of a ruptured suture, but this was resolved through a conservative approach. There was no mortality. Postoperative endoscopy revealed that the anastomosis area was extremely soft, and no abnormalities were observed. Moreover, the only costs related to the anastomosis were for the thread and needles, and although more time was required compared with mechanical anastomosis, the cost was extremely low. CONCLUSIONS: We performed gastroduodenal anastomosis under a total laparoscopic approach by handsewn. This method is economical, because it does not require the use of machinery for anastomosis, and the duodenal stump is short. We believe that this method, which can be performed in a similar manner even for obese patients, can be used as a standard method of anastomosis.


Assuntos
Gastrectomia/métodos , Laparoscopia/métodos , Neoplasias Gástricas/cirurgia , Técnicas de Sutura , Anastomose Cirúrgica/métodos , Duodeno/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Masculino , Suturas
18.
Chem Cent J ; 6(1): 57, 2012 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-22713213

RESUMO

BACKGROUND: Pyrroloquinoline quinone (PQQ), a tricarboxylic acid, has attracted attention as a growth factor, and its application to supplements and cosmetics is underway. The product used for these purposes is a water-soluble salt of PQQ disodium. Although in the past, PQQ disodiumpentahydrates with a high water concentration were used, currently, low hydration crystals of PQQ disodiumpentahydrates are preferred. RESULTS: We prepared a crystal of PQQ disodium trihydrate in a solution of ethanol and water, studied its structure, and analyzed its properties. In the prepared crystal, the sodium atom interacted with the oxygen atom of two carboxylic acids as well as two quinones of the PQQ disodium trihydrate. In addition, the hydration water of the prepared crystal was less than that of the conventional PQQ disodium crystal. From the results of this study, it was found that the color and the near-infrared (NIR) spectrum of the prepared crystal changed depending on the water content in the dried samples. CONCLUSIONS: The water content in the dried samples was restored to that in the trihydrate crystal by placing the samples in a humid environment. In addition, the results of X-ray diffraction (XRD) and X-ray diffraction-differential calorimetry (XRD-DSC) analyses show that the phase of the trihydrate crystal changed when the crystallization water was eliminated. The dried crystal has two crystalline forms that are restored to the original trihydrate crystals in 20% relative humidity (RH). This crystalline (PQQ disodium trihydrate) is stable under normal environment.

19.
Hepatogastroenterology ; 58(105): 257-62, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21510325

RESUMO

BACKGROUND/AIMS: The aim of this study was to evaluate the clinical advantages of Roux-en-Y (R-Y) and Billroth-I (B-I) reconstruction after distal gastrectomy for gastric cancer by examining the postoperative symptoms based on a patient questionnaire and patient nutrition. In addition, this study determined which of the R-Y or B-I procedures is preferable following distal gastrectomy. METHODOLOGY: Fifty-one patients who had undergone R-Y reconstruction and 50 patients who had undergone B-I reconstruction were retrospectively enrolled in this study. The operative and postoperative findings such as operating time, blood loss, complications, and postoperative hospital stay were evaluated as short-term clinical outcomes. Postoperative serum nutrition parameters, transition of body weight, incidence of residual gastritis, and clinical symptoms were evaluated as mid-term clinical outcomes. An assessment of symptoms was based on a questionnaire concerning dumping symptoms, reflux symptoms, food intake, and satisfaction with the operation. RESULTS: No significant differences were observed in the operative and postoperative clinical parameters without stage grouping. The transition of serum nutrition parameters revealed no significant differences between the two groups for the preoperative and postoperative states. Dumping symptoms, reflux symptoms, and abdominal symptoms were less frequent in R-Y patients, but there were no significant differences between the two groups. Moreover, the differences in body weight recovery rates were not found to be statistically significant between two groups. However, the incidence of residual gastritis was significantly less in R-Y patients (21.2%) than in B-I patients (68.8%) (p < 0.05). The questionnaire results regarding food intake and surgery satisfaction were not significantly different between the two groups. CONCLUSIONS: Definite clinical advantages were not recognized in patients with R-Y reconstruction. B-I and R-Y reconstructive procedures should be selected according to the condition of each patient. However, the advantages of these reconstruction procedures following distal gastrectomy would only be revealed in large randomized controlled trials.


Assuntos
Anastomose em-Y de Roux , Gastrectomia/métodos , Gastroenterostomia , Neoplasias Gástricas/cirurgia , Biomarcadores Tumorais/análise , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Feminino , Gastrite/epidemiologia , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Seleção de Pacientes , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Estatísticas não Paramétricas , Inquéritos e Questionários , Fatores de Tempo
20.
J Agric Food Chem ; 59(5): 1705-12, 2011 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-21309575

RESUMO

A kinetic study of the quenching reaction of singlet oxygen ((1)O(2)) with pyrroloquinolinequinol (PQQH(2), a reduced form of pyrroloquinolinequinone (PQQ)), PQQNa(2) (disodium salt of PQQ), and seven kinds of natural antioxidants (vitamin C (Vit C), uric acid (UA), epicatechin (EC), epigallocatechin (EGC), α-tocopherol (α-Toc), ubiquinol-10 (UQ(10)H(2)), and ß-carotene (ß-Car)) has been performed. The second-order rate constants k(Q) (k(Q) = k(q) + k(r), physical quenching and chemical reaction) for the reaction of (1)O(2) with PQQH(2), PQQNa(2), and seven kinds of antioxidants were measured in 5.0 wt % Triton X-100 micellar solution (pH 7.4), using UV-visible spectrophotometry. The k(Q) values decreased in the order of ß-Car > PQQH(2) > α-Toc > UA > UQ(10)H(2) > Vit C ∼ EGC > EC ≫ PQQNa(2). PQQH(2) is a water-soluble antioxidant. The singlet oxygen-quenching activity of PQQH(2) was found to be 6.3, 2.2, 6.1, and 22 times as large as the corresponding those of water-soluble antioxidants (Vit C, UA, EGC, and EC). Further, the activity of PQQH(2) was found to be 2.2 and 3.1 times as large as the corresponding activity of lipid-soluble antioxidants (α-Toc and UQ(10)H(2)). On the other hand, the activity of PQQH(2) is 6.4 times as small as that of ß-Car. It was observed that the chemical reaction (k(r)) is almost negligible in the quenching reaction of (1)O(2) by PQQH(2). The result suggests that PQQH(2) may contribute to the protection of oxidative damage in biological systems, by quenching (1)O(2).


Assuntos
Micelas , Cofator PQQ/química , Oxigênio Singlete/química , Antioxidantes/química , Cinética , Oxirredução , Soluções , Espectrofotometria Ultravioleta
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