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1.
Health Secur ; 21(3): 165-175, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37093031

RESUMO

A COVID-19 patient surge in Japan from July to September 2021 caused a mismatch between patient severity and bed types because hospital beds were fully occupied and patient referrals between hospitals stagnated. Japan's predominantly private healthcare system lacks effective mechanisms to coordinate healthcare providers to address the mismatch. To address the surge, in August 2021, Tokyo Saiseikai Central Hospital started a scheme to exchange patients with other hospitals to mitigate the mismatch. In this article, we outline a retrospective observational study using medical records from a tertiary care medical center that treated severe COVID-19 cases. We describe daily patient admissions to our hospital's COVID-19 beds from July to September 2021, and compared the moving average of daily admissions before and after the exchange scheme was introduced. Bed occupancy reached nearly 100% in late July when the patient surge began and continued to exceed 100% in August when the surge peaked. However, the average daily admission did not decrease in August compared with July: the median daily admission (25th to 75th percentile) during each period was 2 (1 to 2.5) in late July and 3 (2 to 4) in August. The number of patients referred in from secondary care hospitals and the number of patients referred out was balanced in August. During the patient surge, the exchange scheme enabled the hospital to maintain and even increase the number of new admissions despite the bed shortage. Coordinating patient referrals in both directions simultaneously, rather than the usual 1-way transfer, can mitigate such mismatches.


Assuntos
COVID-19 , Humanos , Japão , Ocupação de Leitos , Encaminhamento e Consulta , Centros de Atenção Terciária , Capacidade de Resposta ante Emergências
2.
Acute Med Surg ; 7(1): e614, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33335739

RESUMO

AIM: To clarify how the medical institutions overcame the first wave of coronavirus disease 2019 (COVID-19) in Japan and to discuss its impact on the medical labor force. METHODS: We analyzed questionnaire data from the end of May 2020 from 180 hospitals (102,578 beds) certified by the Japanese Association for Acute Medicine. RESULTS: Acute (emergency) medicine physicians treated severe COVID-19 patients in more than half of hospitals. Emergency medical teams consisted of acute medicine physicians and other specialists. Frontline acute care physicians were concerned about their risk of infection in 80% of hospitals, and experienced stress due to a lack of personal protective equipment. Twenty-six of the 143 hospitals that had a mental health check/consultation system in place indicated that there was a doctor who experienced mental health problems. Of the 37 hospitals without a system, only one hospital was aware of the presence of a doctor complaining of mental health problems. CONCLUSION: Acute care physicians and physicians in other departments experienced high levels of stress as they fought to arrange COVID-19 treatment teams and inpatient COVID-19 wards for infected patients. Medical materials and equipment may be sufficient for a second or third wave; however, active support is needed for the physical and mental care of medical staff. Mental health problems may be missed in facilities without mental check and consultation system.

3.
Acute Med Surg ; 7(1): e592, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33230419

RESUMO

Aim: To investigate and clarify the surge capacity of staff/equipment/space, and patient outcome in the first wave of coronavirus disease (COVID-19) in Japan. Methods: We analyzed questionnaire data from the end of May 2020 from 180 hospitals (total of 102,578 beds) with acute medical centers. Results: A total of 4,938 hospitalized patients with COVID-19 were confirmed. Of 1,100 severe COVID-19 inpatients, 112 remained hospitalized and 138 died. There were 4,852 patients presumed to be severe COVID-19 patients who were confirmed later to be not infected. Twenty-seven hospitals (15% of 180 hospitals) converted their intensive care unit (ICU) to a unit for COVID-19 patients only, and 107 (59%) had to manage both severe COVID-19 patients and others in the same ICU. Restriction of ICU admission occurred in one of the former 27 hospitals and 21 of the latter 107 hospitals. Shortage of N95 masks was the most serious concern regarding personal protective equipment. As for issues that raised ICU bed occupancy, difficulty undertaking or progressing rehabilitation for severe patients (42%), and the improved patients (28%), long-lasting severely ill patients (36%), and unclear isolation criteria (34%) were mentioned. Many acute medicine physicians assisted regional governmental agencies, functioning as advisors and volunteer coordinators. Conclusion: The mortality rate of COVID-19 in this study was 4.1% of all hospitalized patients and 12.5% (one in eight) severe patients. The hospitals with dedicated COVID-19 ICUs accepted more patients with severe COVID-19 and had lower ICU admission restrictions, which could be helpful as a strategy in the next pandemic.

4.
PLoS One ; 15(3): e0228224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32191709

RESUMO

We aimed to determine the characteristics of quantitative pupillary response parameters other than amplitude of pupillary light reflex (PLR) early after return of spontaneous circulation (ROSC) and their implications for predicting neurological outcomes early after cardiac arrest (CA). Fifty adults resuscitated after non-traumatic out-of-hospital CA from four emergency hospitals were enrolled. Pupil diameters, PLR, constriction velocity (CV), maximum CV (MCV), dilation velocity (DV), latency of constriction, and Neurological Pupil index (NPi) were quantitatively measured at 0, 6, 12, 24, 48, and 72 h post-ROSC using an automated pupillometer. Change over time of each parameter was compared between favorable (Cerebral Performance Category [CPC] 1 or 2) and unfavorable neurological outcome (CPC 3-5) groups. Prognostic values of 90-day favorable outcome by these parameters and when combined with clinical predictors (witness status, bystander cardiopulmonary resuscitation, initial shockable rhythm, implementation of target temperature management) were tested. Thirteen patients achieved favorable outcome. CV, MCV, DV (P < 0.001), and NPi (P = 0.005) were consistently greater in the favorable group than in the unfavorable outcome group. Change over time was not statistically different between the groups in all parameters. CV, MCV, DV (ρ = 0.96 to 0.97, P < 0.001, respectively), and NPi (ρ = 0.65, P < 0.001) positively correlated with PLR. The prognostic value of 0-hour CV (area under the curve, AUC [95% confidence interval]: 0.92 [0.80-1.00]), DV (0.84 [0.68-0.99]), and NPi (0.88 [0.74-1.00]) was equivalent to that of PLR (0.84 [0.69-0.98]). Prognostic values improved to AUC of 0.95-0.96 when 0-hour PLR, CV, DV, or NPi was combined with clinical predictors. The 0-hour CV, MCV, and NPi showed equivalent prognostic values to PLR alone/in combination with clinical predictors. Using PLR among several quantitative pupillary response parameters for early neurological prognostication of post-CA patients is a simple and effective strategy.


Assuntos
Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Pupila/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurologia , Prognóstico , Estudos Prospectivos
5.
Acta Crystallogr C Struct Chem ; 74(Pt 10): 1153-1159, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30284982

RESUMO

Disodium guanosine 5'-monophosphate was reported previously to crystallize as both the tetrahydrate and the heptahydrate. We herein report a determination of the molecular and crystal structures of the title tetrahydrated salt, 2Na+·C10H12N5O8P2-·4H2O. It was found that the structure differs markedly from that of the heptahydrate, but greatly resembles that of disodium deoxyguanosine 5'-monophosphate tetrahydrate. The C2'-O2'H moiety of ribose is surrounded by hydrophilic moieties and is disordered over two sites. The sugar puckering mode is O4'-endo-C1'-exo at both sites and the conformation around the C4'-C5' bond is gauche-trans. Powder X-ray diffraction and thermal analyses revealed that the temperature-controlled transition from the tetrahydrate to the anhydride proceeded through three intermediate phases between 40 and 60 °C at 0% relative humidity. Large induction periods were observed.

6.
Resuscitation ; 131: 108-113, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29958957

RESUMO

AIM: To clarify whether quantitative assessment of pupillary light reflexes (PLR) can predict the outcome of post-cardiac arrest (CA) patients during the first 72 h after the return of spontaneous circulation (ROSC). METHODS: Fifty adults resuscitated after non-traumatic out-of-hospital CA (OHCA) (mean age 64.1 years old, 36 males) were enrolled in four emergency hospitals. PLR was sequentially measured at 0, 6, 12, 24, 48, and 72 h after ROSC by an automated portable infrared pupillometry. PLR values for each time point were compared between both survivors and non-survivors, and patients with either favourable (Cerebral Performance Category (CPC) 1 or 2) or unfavourable neurological outcomes. RESULTS: Twenty-three patients survived for 90 days after CA, and 13 patients achieved favourable neurological outcomes. The PLR values of the survivors and patients with favourable neurological outcomes were consistently greater than those of non-survivors (P < 0.001) and those with unfavourable neurological outcomes (P < 0.001), respectively. The change in PLR over time was not statistically different between the outcome groups. The 0-hour PLR best predicted both 90-day survival (AUC = 0.82, cutoff 3%, sensitivity 0.87, specificity 0.80) and favourable neurological outcomes (AUC = 0.84, cutoff 6%, sensitivity 0.92, specificity 0.74). No patient with a 6-hour PLR less than 3% survived for 90 days after CA. CONCLUSIONS: Quantitatively measured PLR was consistently greater in survivors and patients with favourable neurological outcomes during the 72 h after ROSC. Quantitative assessment of PLR at as early as 0 h has a potential role for prognostication in post-CA patients.


Assuntos
Parada Cardíaca Extra-Hospitalar/mortalidade , Reflexo Pupilar/fisiologia , Adulto , Idoso , Reanimação Cardiopulmonar/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Recuperação de Função Fisiológica , Fatores de Tempo
7.
Nanomaterials (Basel) ; 7(8)2017 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-28825641

RESUMO

The inhibitory effect of gallium (Ga) ions on bone resorption and their superior microbial activity are attractive and sought-after features for the vast majority of implantable devices, in particular for implants used for hard tissue. In our work, for the first time, Ga ions were successfully incorporated into the surface of titanium metal (Ti) by simple and cost-effective chemical and heat treatments. Ti samples were initially treated in NaOH solution to produce a nanostructured sodium hydrogen titanate layer approximately 1 µm thick. When the metal was subsequently soaked in a mixed solution of CaCl2 and GaCl3, its Na ions were replaced with Ca and Ga ions in a Ga/Ca ratio range of 0.09 to 2.33. 8.0% of the Ga ions were incorporated into the metal surface when the metal was soaked in a single solution of GaCl3 after the NaOH treatment. The metal was then heat-treated at 600 °C to form Ga-containing calcium titanate (Ga-CT) or gallium titanate (GT), anatase and rutile on its surface. The metal with Ga-CT formed bone-like apatite in a simulated body fluid (SBF) within 3 days, but released only 0.23 ppm of the Ga ions in a phosphate-buffered saline (PBS) over a period of 14 days. In contrast, Ti with GT did not form apatite in SBF, but released 2.96 ppm of Ga ions in PBS. Subsequent soaking in hot water at 80 °C dramatically enhanced apatite formation of the metal by increasing the release of Ga ions up to 3.75 ppm. The treated metal exhibited very high antibacterial activity against multidrug resistant Acinetobacter baumannii (MRAB12). Unlike other antimicrobial coating on titanium implants, Ga-CT and GT interfaces were shown to have a unique combination of antimicrobial and bioactive properties. Such dual activity is essential for the next generation of orthopaedic and dental implants. The goal of combining both functions without inducing cytotoxicity is a major advance and has far reaching translational perspectives. This unique dual-function biointerfaces will inhibit bone resorption and show antimicrobial activity through the release of Ga ions, while tight bonding to the bone will be achieved through the apatite formed on the surface.

8.
Anim Sci J ; 88(7): 1027-1033, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27878891

RESUMO

Streptococcus bovis, an etiologic agent of rumen acidosis in cattle, is a rumen bacterium that can grow in a chemically defined medium containing ammonia as a sole source of nitrogen. To understand its ability to assimilate inorganic ammonia, we focused on the function of glutamate dehydrogenase. In order to identify the gene encoding this enzyme, we first amplified an internal region of the gene by using degenerate primers corresponding to hexameric family I and NAD(P)+ binding motifs. Subsequently, inverse PCR was used to identify the whole gene, comprising an open reading frame of 1350 bp that encodes 449 amino acid residues that appear to have the substrate binding site of glutamate dehydrogenase observed in other organisms. Upon introduction of a recombinant plasmid harboring the gene into an Escherichia coli glutamate auxotroph lacking glutamate dehydrogenase and glutamate synthase, the transformants gained the ability to grow on minimal medium without glutamate supplementation. When cell extracts of the transformant were resolved by blue native polyacrylamide gel electrophoresis followed by activity staining, a single protein band appeared that corresponded to the size of S. bovis glutamate dehydrogenase. Based on these results, we concluded that the gene obtained encodes glutamate dehydrogenase in S. bovis.


Assuntos
Clonagem Molecular , Glutamato Desidrogenase/genética , Rúmen/microbiologia , Streptococcus bovis/enzimologia , Streptococcus bovis/genética , Acidose/microbiologia , Acidose/veterinária , Amônia/metabolismo , Animais , Sequência de Bases , Bovinos , Doenças dos Bovinos/microbiologia , Glutamato Desidrogenase/metabolismo , Reação em Cadeia da Polimerase , Análise de Sequência/métodos , Gastropatias/microbiologia , Gastropatias/veterinária , Streptococcus bovis/metabolismo , Streptococcus bovis/patogenicidade
9.
Acta Crystallogr Sect E Struct Rep Online ; 69(Pt 5): o660, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23723822

RESUMO

In the title compound, C10H19N3O4, the N- and C-termini are protonated and ionized, respectively, and the mol-ecule forms a zwitterion. The main chain is in a folded form. In the crystal, the N-terminal -NH3 (+) group hydrogen bonds to three C-terminal -COO groups and one carbonyl O atom, forming a three-dimensional network. In addition, an N-H⋯O hydrogen bond between the amide groups of the middle glycine residue and a C-H⋯O inter-action continue along the a-axis direction. The side chains of the leucyl residues form a hydro-phobic region along the a axis.

10.
Acta Crystallogr C ; 68(Pt 12): o498-501, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23221255

RESUMO

Crystals of L-leucylglycine (L-Leu-Gly) 0.67-hydrate, C(8)H(16)N(2)O(3)·0.67H(2)O, (I), were obtained from an aqueous solution. There are three symmetrically independent dipeptide zwitterionic molecules in (I) and they are parallel to one another. The hydrogen-bond network composed of carboxylate and amino groups and water molecules extends parallel to the ab plane. Hydrophilic regions composed of main chains and hydrophobic regions composed of the isobutyl groups of the leucyl residues are aligned alternately along the c axis. An imidazolidinone derivative was obtained from L-Leu-Gly and acetone, viz. [(4S)-2,2-dimethyl-4-(2-methylpropyl)-5-oxoimidazolidin-3-ium-1-yl]acetate, C(11)H(20)N(2)O(3), (II), and was crystallized from a methanol-acetone solution of L-Leu-Gly. The unit-cell parameters coincide with those reported previously for L-Leu-Gly dihydrate revealing that the previously reported values should be assigned to the structure of (II). One of the imidazolidine N atoms is protonated and the ring is nearly planar, except for the protonated N atom. Protonated N atoms and deprotonated carboxy groups of neighbouring molecules form hydrogen-bonded chains. The ring carbonyl group is not involved in hydrogen bonding.


Assuntos
Acetatos/química , Dipeptídeos/química , Imidazolidinas/química , Cristalografia por Raios X , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular
11.
J Am Chem Soc ; 132(13): 4528-9, 2010 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-20222711

RESUMO

A spin-polarized donor, BTBN, which is a dibromotetrathiafulvalene derivative containing a nitronyl nitroxide group in a cross-conjugated manner, was prepared. Upon hole injection from an electrode, the neutral microcrystals of BTBN exhibited nonlinear I-V characteristics that were interpreted in terms of the space-charge-limited conduction (SCLC) mechanism. Moreover, the resistance of BTBN decreased upon application of a magnetic field below 30 K and exhibited a giant negative magnetoresistance of (R(H) - R(0))/R(0) = -76% at 2 K under 5 T. These results show that the transport of carriers in the neutral unicomponent radical crystal can be controlled by the external magnetic field. These findings are important as a basis for developing molecule-based spin electronic devices.


Assuntos
Compostos Heterocíclicos/química , Magnetismo , Óxidos de Nitrogênio/química , Cristalização , Condutividade Elétrica , Modelos Moleculares , Estrutura Molecular , Temperatura
12.
J Phys Chem A ; 112(30): 7055-63, 2008 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-18610952

RESUMO

Fourier analysis, using the atomic trajectory calculated by molecular dynamics simulation at 300 K, is applied to the study of low-frequency phonons of guanine dihydrate. The vibrational modes of guanine bases are analyzed, and the optically active modes associated with the guanine moieties are extracted. There are a few significant peaks in the low-frequency region. A possible assignment of the Raman active mode near 27 cm(-1), whose origin would be common to the S-mode of DNA double helices, is discussed.

13.
Nihon Rinsho ; 66(2): 355-9, 2008 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-18265459

RESUMO

Patients with coronary artery aneurysms caused by Kawasaki disease are at increased risk of coronary thrombosis and ischemia. To prevent coronary thrombosis, long-term anti-thrombosis using anti-platelet drugs, such as aspirin, dipyridamole, ticlopidine, clopidogrel, and abciximab, with or without warfarin is recommended by official guidelines. In fact, aspirin or aspirin with warfarin are the most frequently administered regimen in these patients with coronary aneurysms. However, there has been paucity of data and no randomized controlled study to determine the efficacy of these drugs. This short article attempts to summarize the efficacy and safety of these drugs based on currently available literatures and our multi-institutional experience.


Assuntos
Aneurisma Coronário/tratamento farmacológico , Trombose Coronária/prevenção & controle , Síndrome de Linfonodos Mucocutâneos/complicações , Inibidores da Agregação Plaquetária/uso terapêutico , Aspirina/uso terapêutico , Pré-Escolar , Humanos , Lactente , Varfarina/uso terapêutico
14.
Biosci Biotechnol Biochem ; 69(2): 357-63, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15725662

RESUMO

A new ergothioneine derivative named beta-hydroxyergothioneine was isolated from the mushroom Lyophyllum connatum. Ergothioneine,N-hydroxy-N',N'-dimethylurea, and connatin (N-hydroxy-N',N'-dimethylcitrulline) were also isolated. All the compounds displayed the ability to scavenge free radicals, based on a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. Structural determination, including the absolute stereochemistry of beta-hydroxyergothioneine, was achieved by spectroscopic analysis and X-ray crystallography. The radical scavenging activity of beta-hydroxyergothioneine was almost the same as that of ergothioneine. beta-Hydroxyergothioneine showed the greatest protective activity against carbon tetrachloride-induced injury in primary culture hepatocytes.


Assuntos
Agaricales/química , Ergotioneína/análogos & derivados , Ergotioneína/isolamento & purificação , Sequestradores de Radicais Livres/isolamento & purificação , Hepatócitos/efeitos dos fármacos , Animais , Compostos de Bifenilo , Tetracloreto de Carbono/antagonistas & inibidores , Células Cultivadas , Ergotioneína/farmacologia , Sequestradores de Radicais Livres/farmacologia , Hidrazinas , Estrutura Molecular , Picratos , Ratos , Ratos Wistar
15.
J Phys Chem B ; 109(3): 1304-12, 2005 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-16851095

RESUMO

The dynamics of crystal water molecules of guanosine dihydrate are investigated in detail by molecular dynamics (MD) simulation. A 2 ns simulation is performed using a periodic boundary box composed of 4 x 5 x 8 crystallographic unit cells and using the particle-mesh Ewald method for calculation of electrostatic energy. The simulated average atomic positions and atomic displacement parameters are remarkably coincident with the experimental values determined by X-ray analysis, confirming the high accuracy of this simulation. The dynamics of crystal water are analyzed in terms of atomic displacement parameters, orientation vectors, order parameters, self-correlation functions of the orientation vectors, time profiles of hydrogen-bonding probability, and translocations. The simulation clarifies that the average structure is composed of various stable and transient structures of the molecules. The simulated guanosine crystal forms a layered structure, with four water sites per asymmetric unit, classified as either interlayer water or intralayer water. From a detailed analysis of the translocations of water molecules in the simulation, columns of intralayer water molecules along the c axis appear to represent a pathway for hydration and dehydration by a kind of molecular valve mechanism.


Assuntos
Simulação por Computador , Guanosina/química , Cristalização , Cristalografia por Raios X , Ligação de Hidrogênio , Cinética , Modelos Químicos , Modelos Moleculares , Fatores de Tempo , Água/química
16.
Pediatr Allergy Immunol ; 15(5): 459-68, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15482523

RESUMO

Interleukin (IL)-10 is a cytokine that regulates inflammatory responses. We studied the role of IL-10 in the development of tolerance to Dermatophagoides farinae in asthma patients in remission, since asthma improves in most children during adolescence. The spontaneous production of IL-10 by cultured peripheral blood mononuclear cells (PBMC) was higher in patients with active asthma than in normal subjects. IL-10 production decreased when 1 microg/ml D. farinae was added to cultures, but increased again in a dose-dependent manner when higher concentrations of D. farinae were added. In patients with remission of asthma, IL-10 production was lower than in patients with active asthma. However, production of IL-10 showed a reciprocal increase in the presence of 1 microg/ml D. farinae, and decreased again at 10 and 50 microg/ml D. farinae. Such alterations were not observed in normal subjects. Cell lines established from patients asthma in remission showed higher IL-10 production when compared with that by cell lines from normal subjects or patients with active asthma when the cells were stimulated by D. farinae at 1 or 10 microg/ml. Neutralization of IL-10 led to revival of the D. farinae-specific proliferative response of PBMC from patients in remission, which was otherwise decreased. The increase of IL-10 production stimulated by D. farinae was inhibited by addition of an anti-IL-10 antibody. In contrast, antigen-induced interferon (IFN)-gamma production, which was increased by D. farinae stimulation when patients were in remission, did not increase after treatment with anti-IL-10, although spontaneous IFN-gamma production increased to the level seen after D. farinae stimulation. The reduced IL-4 production by cells from patients in remission after stimulation with D. farinae antigen, which was significantly higher in active patients, was not reversed by neutralization of IL-10. The D. farinae-induced IL-10/IL-4 production ratio, but not the IL-10/IL-5 production ratio, may be a significant indicator for evaluation of whether a patient has been in remission. In conclusion, D. farinae-specific anergy of T cells is likely to be induced by increased levels of IL-10 and IFN-gamma that are initially produced by specific T cells after exposure to relevant mite allergen in patients in remission.


Assuntos
Antígenos de Dermatophagoides/farmacologia , Asma/imunologia , Interleucina-10/biossíntese , Linfócitos/imunologia , Pyroglyphidae/imunologia , Adolescente , Adulto , Antígenos de Dermatophagoides/imunologia , Células Cultivadas , Criança , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Técnicas In Vitro , Interferon gama/biossíntese , Interleucina-4/biossíntese , Interleucina-5/biossíntese , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Remissão Espontânea
17.
Eur J Pharmacol ; 474(2-3): 273-81, 2003 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-12921874

RESUMO

A new macrolide, roxithromycin, may be an effective treatment for asthma. Lymphocyte apoptosis is impaired in patients with asthma, while spontaneous apoptosis increases during remission, and such changes may be involved in the onset and remission of mite-sensitive asthma. Lymphocyte apoptosis was evaluated by incubating cells from patients with asthma in the presence of roxithromycin. Low concentrations of roxithromycin (1-500 ng/ml) augmented the early, but not late, phase of apoptosis in Dermatophagoides farinae-stimulated peripheral blood mononuclear (PBM) cells, while high concentrations of roxithromycin (1 microg/ml; 6 microg/ml is the maximum serum level) augmented both the early and late phases of apoptosis. In both unstimulated and phytohemagglutinin-stimulated cells, roxithromycin did not significantly affect the induction of apoptosis. In cells from normal subjects, roxithromycin did not affect the induction of apoptosis. Other antibiotics, including cefazolin and ampicillin, did not cause significant induction of apoptosis. Fas ligand, but not Fas receptor, expression on D. farinae-stimulated cells was up-regulated after stimulation with 1 microg/ml roxithromycin, while Bcl-2 expression on both unstimulated and D. farinae-stimulated cells showed a decrease after the same treatment. Roxithromycin can induce apoptosis of D. farinae-activated lymphocytes in patients with D. farinae-sensitive asthma. Induction of the Fas/Fas ligand system and reduced Bcl-2 expression were involved in the promotion of apoptosis by roxithromycin treatment.


Assuntos
Apoptose/efeitos dos fármacos , Asma/tratamento farmacológico , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Pyroglyphidae/efeitos dos fármacos , Pyroglyphidae/imunologia , Roxitromicina/farmacologia , Adolescente , Apoptose/imunologia , Asma/patologia , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Roxitromicina/química , Roxitromicina/uso terapêutico
18.
J Comput Chem ; 24(7): 826-41, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12692792

RESUMO

A technique for performing normal vibrational analysis for biological macromolecules using general internal coordinates is proposed. The technique is based on the conventional algorithm for calculating the second derivatives of potential and kinetic energies using intramolecular dihedral angles, intermolecular translation, and rotation as variables [Braun, W. et al., J Phys Soc Jpn 1984, 53, 3269]. We extend the algorithm to include more general internal coordinates, bond stretching, angle bending, and so forth, without assuming two-body interactions. The essential point is the separation of the variables for potential functions and vibrational analysis. With our technique, we can arbitrarily choose any combination of internal coordinates as variables, free from the functional form of potential energy. We can analyze complex systems such as a multiple molecular system including solvents or a transition state of chemical reactions. In addition, mixed use of the potentials of molecular mechanics and quantum chemistry is possible.

19.
Acta Crystallogr D Biol Crystallogr ; 59(Pt 2): 378-80, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12554959

RESUMO

A fucose-specific lectin from Aleuria aurantia was crystallized in its native form and was also cocrystallized with HgCl(2). Crystallization was performed using the sitting-drop vapour-diffusion method with ammonium sulfate as a precipitant. Both the Hg-free native crystals and the Hg cocrystals belong to the hexagonal space group P6(5)22. The unit-cell parameters for the Hg-free form are a = 84.0, c = 250.1 A and for the Hg cocrystals are a = 83.9, c = 254.3 A. Both forms of the crystals diffract X-rays to 2.3 A resolution and are suitable for high-resolution crystal structure determination. Initial phasing was successfully performed by the MAD method using the Hg cocrystals and the electron density obtained was good enough for model building.


Assuntos
Lectinas/química , Ascomicetos/química , Cristalização/métodos , Cristalografia por Raios X/métodos , Proteínas Fúngicas/química , Cloreto de Mercúrio/química , Eletricidade Estática
20.
J Asthma ; 39(7): 591-601, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12442948

RESUMO

Apoptosis regulates inflammatory cell survival in allergic inflammation, and decreased apoptosis contributes to the chronicity of inflammation. To investigate the mechanisms of onset and remission of mite-sensitive childhood asthma, we evaluated peripheral blood mononuclear cell apoptosis in patients with asthma and in remission. There was a similar percentage of hypodiploid cells in unstimulated mononuclear cell cultures from patients with active asthma (29.5+/-5.0%) and normal individuals (25.9+/-4.9%). In contrast, the percentage increased in patients in remission (44.5+/-3.2%). In Dermatophagoides farinae (Df) antigen-stimulated mononuclear cell, the stimulation index was lower in patients with active asthma (0.95+/-0.06%) than in normal individuals (1.31+/-0.16%). In contrast to active patients, the proportion of hypodiploid cells stimulated with Df in patients with remission was equivalent to that of normal controls. After phytohemaglutinin (PHA) stimulation, the percentage of hypodiploid cells in patients with active asthma (35.1+/-3.2%) was also lower than in normal individuals (48.5+/-4.3%) or patients in remission (49.5+/-5.7%). Apoptosis occurred predominantly in CD8+, but not CD4+, cells in patients in remission. Interleukin IL-2 inhibited apoptosis in Df-activated cells in normal individuals, whereas IL-2 did not inhibit apoptosis in cells from patients in remission as well as with active asthma. The expression of Fas receptors on resting mononuclear cells was similar in the three groups. However, Fas receptor expression in Df-stimulated mononuclear cells was greater in patients with active asthma than in healthy individuals. In patients with remission that was equivalent to healthy controls. The PHA increased Fas expression to a similar degree in the three groups. With regard to Fas ligand, the expression was lower in unstimulated cultured mononuclear cells from patients than in normal individuals. In patients in remission that was comparable to normal individuals. The Df stimulation upregulated the Fas ligand in patients with active asthma, and downregulated it in patients in remission. In conclusion, apoptosis in Df-stimulated mononuclear cells is impaired in patients with active asthma, while spontaneous apoptosis of CD8+ cells in vivo is augmented in patients in remission, and may be involved in the onset and remission of mite-sensitive asthma.


Assuntos
Apoptose , Asma/imunologia , Leucócitos Mononucleares/imunologia , Adolescente , Animais , Criança , Dermatophagoides farinae/imunologia , Feminino , Humanos , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptor fas/metabolismo
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