RESUMO
It is commonly accepted that the presence of high amounts of maternal T cells excludes Omenn syndrome (OS) in severe combined immunodeficiency (SCID). We report a SCID patient with a novel mutation in the recombination activating gene (RAG)1 gene (4-BP DEL.1406 TTGC) who presented with immunodeficiency and OS. Several assays, including representatives of specific T cell receptors (TCR), Vß families and TCR-γ rearrangements, were performed in order to understand more clearly the nature and origin of the patient's T cells. The patient had oligoclonal T cells which, based on the patient-mother human leucocyte antigen (HLA)-B50 mismatch, were either autologous or of maternal origin. These cell populations were different in their numbers of regulatory T cells (T(reg)) and the diversity of TCR repertoires. This is the first description of the co-existence of large amounts of clonal expanded autologous and transplacental-acquired maternal T cells in RAG1-deficient SCID.
Assuntos
Evolução Clonal , Proteínas de Homeodomínio/genética , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Análise Mutacional de DNA , Humanos , Imunofenotipagem , Mutação , Fenótipo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/genética , Receptores de Antígenos de Linfócitos T gama-delta/metabolismoRESUMO
BACKGROUND: The diagnosis of extranodal natural killer (NK)/T-cell lymphoma (NK/T-cell lymphoma) is often difficult and any delay in its diagnosis leads to a worsened prognosis. We analysed the factors that make the diagnosis of this type of tumour difficult. METHODOLOGY/PRINCIPAL: We retrospectively reviewed the medical records of 20 patients with NK/T-cell lymphoma treated in our department, and assessed the clinical features and laboratory findings of the cases. Moreover, we classified factors related to delays in diagnosing NK/T cell lymphoma as follows: (1) insufficient specimen size, (2) massive necrosis, (3) large number of inflammatory cells, and (4) poor atypia. We selected cases requiring two or more biopsies for correct diagnosis and checked which factors were the main cause of misdiagnosis. RESULTS: The average period required for a correct diagnosis was 12.8 months. The most frequent factor leading to diagnostic delay was inflammatory cell infiltration. Massive necrosis and poor atypia were also important factors in diagnostic delay. CONCLUSIONS: In cases with necrotic lesions of the nose or pharynx, the possibility of NK/T cell lymphoma should be explored and samples, of as large a size as possible, should be obtained together with EBER-ISH for pathological examination. Repeat biopsies should also be performed for diagnosis.
Assuntos
Linfoma Extranodal de Células T-NK/diagnóstico , Neoplasias Otorrinolaringológicas/diagnóstico , Adulto , Idoso , Biópsia , Diagnóstico Tardio , Diagnóstico Diferencial , Endoscopia , Feminino , Humanos , Linfoma Extranodal de Células T-NK/complicações , Linfoma Extranodal de Células T-NK/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias Otorrinolaringológicas/complicações , Neoplasias Otorrinolaringológicas/terapia , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: This study aimed to predict eosinophilic chronic rhinosinusitis prognosis by investigating changes in the blood eosinophil count and other disease biomarkers after surgery. METHODS: Blood eosinophil numbers and serum interleukin-5 levels were measured in 22 eosinophilic chronic rhinosinusitis patients before and after functional endoscopic sinus surgery, and compared with equivalent measures in non-eosinophilic chronic rhinosinusitis patients and chronic rhinosinusitis without polyps patients. Differences between well-controlled eosinophilic chronic rhinosinusitis patients and those who experienced recurrence were also assessed. RESULTS: Blood eosinophil numbers and serum interleukin-5 level decreased after surgery in eosinophilic chronic rhinosinusitis patients. In this patient group, blood eosinophil counts before surgery were significantly higher in patients who experienced recurrence (825.7 ± 26.1 vs 443.9 ± 76.6 cells/µl, p < 0.05), and decreased significantly after surgery (825.7 ± 26.1 vs 76.7 ± 25.8 cells/µl, p < 0.05). CONCLUSION: Blood eosinophil numbers may reflect disease severity in eosinophilic chronic rhinosinusitis patients and their prognosis after surgery.
Assuntos
Eosinofilia/sangue , Interleucina-5/sangue , Seios Paranasais/cirurgia , Rinite/cirurgia , Sinusite/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Endoscopia , Eosinofilia/imunologia , Eosinófilos , Feminino , Humanos , Interleucina-5/imunologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Rinite/sangue , Rinite/imunologia , Sinusite/sangue , Sinusite/imunologia , Resultado do Tratamento , Adulto JovemRESUMO
The effects of hydrogen peroxide were studied on isolated rabbit mesenteric small artery; rabbit superior mesenteric artery and mouse aorta were also studied as reference tissues. For mesenteric small artery, hydrogen peroxide (1 to 100 microM) relaxed a norepinephrine-stimulated artery in a concentration-dependent manner. The relaxation was not significantly affected by removal of the endothelium and was less pronounced in arteries contracted with high-KCl solution plus norepinephrine than in those contracted with norepinephrine alone. The relaxation response to hydrogen peroxide was increased by isobutylmethylxanthine and zaprinast, inhibited by diclofenac, methylene blue and dithiothreitol and unaffected by atropine, tetraethylammonium, superoxide dismutase, deferoxamine, dimethyl sulfoxide or the Rp stereoisomer of adenosine cyclic monophosphothioate. Hydrogen peroxide shifted concentration-contractile response curves for norepinephrine to the right and downwards. Norepinephrine and caffeine elicited a transient, phasic contraction of the mesenteric small artery exposed for 0.5, 1 and 2 min to a Ca2+-free solution. Hydrogen peroxide inhibited the norepinephrine-induced contraction, and to a lesser extent the caffeine-induced contraction, and verapamil did not alter the contraction to norepinephrine. These pharmacological properties of hydrogen peroxide were similar to those of 8-bromo cGMP; 8-bromo cGMP inhibited more potently the norepinephrine-induced than the KCl-induced contraction and the contraction elicited by norepinephrine in Ca2+-free solution. The present results suggest that hydrogen peroxide induces endothelium-independent relaxation of the rabbit mesenteric small artery precontracted with norepinephrine. The effects of hydrogen peroxide may be at least in part mediated by cGMP and cyclooxygenase products in the vascular smooth muscles now used.
Assuntos
Peróxido de Hidrogênio/farmacologia , Artérias Mesentéricas/fisiologia , Músculo Liso Vascular/fisiologia , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Acetilcolina/farmacologia , Animais , Cafeína/farmacologia , Quelantes/farmacologia , Relação Dose-Resposta a Droga , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiologia , Sequestradores de Radicais Livres/farmacologia , Glucose Oxidase/metabolismo , Técnicas In Vitro , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Camundongos , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Nitroarginina/farmacologia , Norepinefrina/farmacologia , Cloreto de Potássio/farmacologia , Coelhos , Superóxido Dismutase/farmacologia , Vasoconstritores/farmacologia , Vasodilatadores/farmacologiaRESUMO
Rats having a non-necrotic damaged liver or a necrotic damaged liver produced by D-galactosamine administration were restrained in water for 0.5, 1, 2, 4, 6, 8 and 12 hours. Serial changes in intrahepatic energy metabolism were compared with those in normal liver. Energy charge, which represents the degree of equilibrium between the energy producing and consuming systems, and cyclic AMP, an intracellular messenger mediating the action of hormones, showed biphasic increases before and after 2 hr in the damaged livers. The lactate/pyruvate ratio, which reflects the cytosolic redox state, markedly increased at 0.5 hr in the damaged livers but returned to the pre-stress level after 1 hr in the non-necrotic damaged liver and after 4 hr in the necrotic damaged liver, showing a transient reduced state. The beta-hydroxybutyrate/acetoacetate ratio, which represents the mitochondrial redox state, decreased at 0.5 hr and returned to the pre-stress level at 1 hr in the non-necrotic damaged liver, exhibiting a transient oxidized state. However, in the necrotic damaged liver, the value decreased at 0.5 hr remained low thereafter, demonstrating a persistent oxidized state. These findings show that, in severely damaged liver, stress has more marked effects on hepatic energy metabolism.
Assuntos
Metabolismo Energético , Hepatopatias/metabolismo , Estresse Fisiológico/metabolismo , Acetilcoenzima A/metabolismo , Animais , Doença Hepática Induzida por Substâncias e Drogas , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Galactosamina , Corpos Cetônicos/metabolismo , Lactatos/metabolismo , Ácido Láctico , Hepatopatias/patologia , Masculino , Piruvatos/metabolismo , Ácido Pirúvico , Ratos , Ratos EndogâmicosRESUMO
Three cases of "spontaneous" pneumocephalus suspected to have resulted from aerobic bacteremia caused by Enterobacter cloacae, Escherichia coli, and Klebsiella aerogenes are reported. In two cases, the E. cloacae and K. aerogenes were isolated from the cerebrospinal fluid. These cases were characterized by a rapid accumulation of air, without niveau, in the subarachnoid space and ventricles.
Assuntos
Abscesso Encefálico/complicações , Infecções por Enterobacteriaceae , Infecções por Escherichia coli , Infecções por Klebsiella , Pneumocefalia/etiologia , Sepse/complicações , Adulto , Enterobacter , Feminino , Humanos , Klebsiella pneumoniae , Masculino , Pessoa de Meia-Idade , Pneumocefalia/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: We examined prognostic factors and outcome of the primary treatment in patients with adenoid cystic carcinoma (ACC) of the head and neck. METHODS: Twenty patients with ACC of the head and neck who had been treated in our institution from 1985 to 1998 were enrolled in this study. Disease-specific survival rate was analyzed by the Kaplan-Mejer method, and the log-rank test was applied to compare the survival rates. RESULTS: The overall 5- and 10-year survival rates determined by Kaplan-Meier analysis were 81 and 57%, respectively. Patients with major salivary gland ACC obtained the best 10-year survival rate (83%), while those with paranasal sinus ACC had the worst survival rate (33%). Predominance of the solid component on pathological examination might indicate a worse prognosis. Our study revealed that postoperative radiotherapy could yield better control of the lesion focus. Chemotherapy failed in some patients and was not dramatically effective by itself. CONCLUSIONS: The long-term prognosis of ACC was poor. Long-term follow-up is necessary for better prognosis of patients treated with radical treatment regimens.
Assuntos
Carcinoma Adenoide Cístico/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/secundário , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
We reported a case of 69-year-old female presenting with clinically typical TTP which was treated with Ticlopidine and plasma exchanges four times in total and resulted in successful improvement of her clinical state. The first chromosomal analysis of lymphocytes in the peripheral blood of the patient revealed abnormal patterns of 45, XO/46, XX/47, XXX, the second, 45, XO/46, XX/47, XXX/47.XX, + 21. Measurement of FITC-labelled fibrinogen antibody against the fibrinogen combined with platelet glycoprotein GP IIb/IIIa complex using flow cytometry showed an apparently increased positive rate 76.2% for the platelet of the patient, compared with that of 31.9% for the control. From the comparative study of the platelet agglutination of the platelet rich plasma (PRP) derived from the citrated-added complete blood taken from the patient to whom Ticlopidine was given, added with adenosine-5'-diphosphate (ADP), collagen or acetyl glyceryl ether phosphoryl choline (AGEPC) as the reagents and that of normal control, it was shown that for AGEPC increased. Thus, increased reaction specific to AGEPC in addition to activated platelet was demonstrated in the present study.
Assuntos
Aberrações Cromossômicas , Troca Plasmática , Púrpura Trombocitopênica Trombótica/genética , Idoso , Feminino , Humanos , Púrpura Trombocitopênica Trombótica/terapiaRESUMO
A clinical study of 107 patients with nasal allergies who were treated at Kushiro General Hospital between April 1998 and March 2000 was performed. Radioallergosorbent tests (RAST), X-rays, and nasal smears for the detection of eosinophilia were performed to obtain a diagnosis of nasal allergy. The patients (50 males, 57 females) ranged in age from 3 to 71 years. The RAST was positive for timothy in 22.4% of the patients, 14.0% for birch and 12.1% for mugwort. The most common pollinosis allergen in the Kushiro area was grass pollen. Other pollinosis allergens were birch pollen and mugwort pollen. We measured the daily count of dispersed birch pollen and timothy pollen in Kushiro and Sapporo. Birch pollen and timothy pollen was dispersed earlier in Kushiro than in Sapporo. Nasal allergies in the Kushiro area appear to be related to local characteristics, such as climate and geographical features.
Assuntos
Rinite Alérgica Sazonal/diagnóstico , Adolescente , Adulto , Idoso , Animais , Gatos , Criança , Pré-Escolar , Clima , Cães , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pólen/imunologia , Teste de Radioalergoadsorção , Rinite Alérgica Sazonal/epidemiologia , Rinite Alérgica Sazonal/imunologia , Estações do AnoRESUMO
Effects of urinary trypsin inhibitor (UTI) on the number, morphology and function of platelets under septic state were studied in rat models of cecal ligation and puncture (CLP). At formation of CLP, 5,000 U/kg/h of UTI was serially administered intraperitoneally and blood was sampled after 16 hours. Comparative study among sham-operation group, CLP group, and CLP + UTI group revealed: 1) inhibition of the platelets of platelet counts and appearance of large-sized, active platelets by UTI in the CLP + UTI group, 2) increase of platelet maximum aggregation rate (MAR) by ADP and increase of collagen in the CLP group, while inhibition in the CLP + UTI group and 3) by HPLC evaluation of adenine nucleotide in the platelet, increased levels of total ATP and ADP in the CLP group, particularly, increases of ATP in the metabolic pool and ADP in the granular pool. CLP + UTI group did not show these changes in the adenylate pool. UTI was thus considered to stabilize the platelet cycle in sepsis. Platelets under septic state might be hyperactive, and thrombosis is easy to occur. UTI administration might work for maintaining constancy of the platelet internal environment and improve septic state because adenine nucleotide level in the platelet did not change in the CLP + UTI group through changed in the CLP group.
Assuntos
Plaquetas/fisiologia , Sepse/sangue , Inibidores da Tripsina/urina , Nucleotídeos de Adenina/sangue , Animais , Plaquetas/análise , Plaquetas/patologia , Modelos Animais de Doenças , Masculino , Agregação Plaquetária , Contagem de Plaquetas , Ratos , Ratos Endogâmicos , Sepse/fisiopatologiaRESUMO
BACKGROUND AND PURPOSE: Corticosteroid insensitivity is a major therapeutic problem for some inflammatory diseases including chronic obstructive pulmonary disease (COPD), and it is known to be induced by reduced histone deacetylase (HDAC)-2 activities via activation of the phosphoinositide 3-kinase (PI3K) pathway. The aim of this study is to evaluate effects of a novel macrolide/fluoroketolide, solithromycin (SOL, CEM-101), on corticosteroid sensitivity induced by oxidative stress. EXPERIMENTAL APPROACH: Corticosteroid sensitivity was determined by IC50/EC50 of dexamethasone (Dex) on TNF-α-induced CXCL8 production in U937 monocytic cell line and peripheral blood mononuclear cells (PBMC) from COPD patients. Activities of HDAC and protein phosphatase 2A (PP2A) were measured by fluorescence-based assay in cells exposed to hydrogen peroxide (H2O2). We also investigated steroid insensitive airway neutrophilia in cigarette smoke exposed mice in vivo. KEY RESULTS: SOL (10 µM) restored Dex sensitivity in PBMC from COPD patients, H2O2-treated U937 cells and phorbol 12-myristate 13-acetate-differentiated U937 cells. In addition, SOL restored HDAC activity with concomitant inhibition of Akt phosphorylation as surrogate marker of PI3K activation. The inhibition of Akt phosphorylation by SOL was due to increased PP2A phosphatase activity, which was reduced in COPD and oxidative stress model. Other known macrolides, such as eryhthromycin, clarithromycin and azithromycin, were significantly less effective in these responses. In cigarette smoke-exposed mice, SOL (100 mg kg(-1), po) showed significant but weak inhibition of neutrophilia, whereas Dex (10 mg kg(-1), p.o.) showed no such effect. However, a combination of SOL and Dex inhibited neutrophilia by over 50%. CONCLUSIONS AND IMPLICATIONS: SOL has potential as novel therapy for corticosteroid-insensitive diseases such as COPD.
Assuntos
Corticosteroides/farmacologia , Antibacterianos/farmacologia , Dexametasona/farmacologia , Resistência a Medicamentos/efeitos dos fármacos , Macrolídeos/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Triazóis/farmacologia , Animais , Células Cultivadas , Histona Desacetilase 2/metabolismo , Humanos , Peróxido de Hidrogênio/farmacologia , Interleucina-8/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neutrófilos , Estresse Oxidativo/efeitos dos fármacos , Proteína Fosfatase 2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Fumaça/efeitos adversos , Nicotiana , Fator de Necrose Tumoral alfa/farmacologia , Células U937RESUMO
A new ordered fullerene phase encapsulated by large-diameter CNTs is systematically investigated by combining a growth technique by chemical vapour deposition, high-resolution transmission electron microscopy and molecular-dynamics simulations. In contrast to fullerenes in smaller (1-2 nm) diameter CNTs, where fullerenes are packed in linear or helical chains, fullerenes form a nanoscale cylinder in double-walled CNTs with diameters of â¼4 nm. The fullerenes were shown to form a nanocylinder with a side wall that resembled the (111) plane of solid C(60). This ordered phase is different from peapods or fullerene solids known so far, and a result of the interaction between the CNT wall and fullerenes. This finding will open up a new field of fullerene science.
RESUMO
A high-performance liquid chromatographic (HPLC) method for the determination of L-carnitine in clamped and frozen rat livers is described. L-carnitine + acetyl-CoA in equilibrium with acetyl-L-carnitine + CoASH Using the above enzymatic reaction, release of CoASH is stoichiometric with the L-carnitine added. The present method has made possible the determination of carnitine in liver tissues, which is difficult by the conventional enzymatic spectrophotometric method using 5,5'-dithiobis(2-nitrobenzoic acid), owing to acetyl-CoA hydrolysis during prolonged incubations at pH 7.8.
Assuntos
Carnitina/análise , Fígado/análise , Acetilcoenzima A/análise , Acil Coenzima A/análise , Animais , Carnitina O-Acetiltransferase/metabolismo , Coenzima A/análise , Concentração de Íons de Hidrogênio , Mercaptoetanol/metabolismo , RatosRESUMO
A method for the determination of carnitine palmitoyltransferase I (CPT I; EC 2.3.1.19) in isolated rat liver mitochondria by reversed-phase high-performance liquid chromatography is described. Enzyme activity is assayed by direct determination of coenzyme A (CoA) released from palmitoyl-CoA within 60 min by a linear gradient system. CPT 1 in rat liver mitochondria can be assayed from only 30 micrograms of mitochondrial protein per millilitre of assay mixture. The changes in the kinetic parameters of CPT I, including Ki for malonyl-CoA, resulting from the fasting-feeding cycle are also discussed.
Assuntos
Aciltransferases/análise , Carnitina O-Palmitoiltransferase/análise , Animais , Cromatografia Líquida de Alta Pressão , Jejum , Cinética , Masculino , Mitocôndrias Hepáticas/enzimologia , Ratos , Ratos Endogâmicos , Espectrofotometria UltravioletaRESUMO
The incidence of duodenal varices is exceedingly rare. A case of bleeding duodenal varices located in the third portion of the duodenum, secondary to idiopathic portal hypertension, which was successfully treated by surgery, is presented herein. Diagnosis was suspected at superior mesenteric angiography and was subsequently confirmed by endoscopy. A review of the literature reveals only 105 such cases in the world. While the duodenal bulb is the most common site of duodenal varices, the second portion of the duodenum appears to be the next most common site but duodenal varices in the other portions are extremely rare. From all of the possible causes of duodenal varices, liver cirrhosis remains the predominant etiological factor in 31 cases.
Assuntos
Duodeno/irrigação sanguínea , Hemorragia Gastrointestinal/etiologia , Varizes/complicações , Feminino , Humanos , Pessoa de Meia-Idade , Ruptura EspontâneaRESUMO
A case of a 73 year old man who was preoperatively diagnosed as possibly having myelolipoma is presented herein. Adrenal myelolipoma is an uncommon benign tumor of which only 74 foreign cases and 43 Japanese cases have been previously reported in the literature dealing with surgically removed myelolipomas. The most consistent complaint of the adrenal myelolipoma sufferer is abdominal pain, caused by hemorrhaging in the tumor, and many cases are associated with obesity, hypertension and/or diabetes mellitus. There is now an increasing number of such cases being diagnosed during abdominal scanning with ultrasonography or computerized tomography for unrelated problems, whereupon the myelolipoma is usually surgically resected. With the availability of modern scanning techniques and fine needle biopsy, however, it should be possible to adopt a more conservative approach to the management of asymptomatic adrenal myelolipoma. Nevertheless, symptomatic or large tumors, must be removed since there is a high risk of spontaneous hemorrhage.
Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Lipoma/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Glândulas Suprarrenais/patologia , Idoso , Humanos , Lipoma/patologia , MasculinoRESUMO
The occurrence of rhabdomyolysis and acute renal failure associated with viral infections is uncommon. We report a case of a 17-year-old female suffering from rhabdomyolysis caused by echovirus 9 in which the patient recovered after being treated for acute renal failure with hemodialysis. Among 42 cases of virus-induced rhabdomyolysis review in Japanese and English literatures, influenza virus is the most common cause of rhabdomyolysis, coxsackie virus tends to be next most common cause. Renal failure was recognized in 31 of the cases.
Assuntos
Injúria Renal Aguda/etiologia , Infecções por Echovirus/complicações , Rabdomiólise/complicações , Adolescente , Anticorpos Antivirais/análise , Echovirus 9/isolamento & purificação , Infecções por Echovirus/diagnóstico , Feminino , Humanos , Edema Pulmonar/complicaçõesRESUMO
The activities of palmitoyl-coenzyme A (CoA) synthetase, carnitine acetyltransferase (CAT), and carnitine palmitoyltransferase (CPT) and the levels of ketone bodies, reduced coenzyme A (CoASH), carnitine, and their esters, which are involved in fatty acid metabolism, in rat liver and plasma were measured after the administration of Escherichia coli lipopolysaccharide (LPS). We also studied the effect of L-carnitine treatment before LPS administration on survival and on hepatic fatty acid metabolism. The activities of CAT and CPT and the concentrations of ketone bodies, CoA, and carnitine derivatives (except for malonyl-CoA) declined in the liver after LPS administration. The activity of palmitoyl-CoA synthetase was changed little after LPS administration, and the level of hepatic malonyl-CoA increased significantly, suggesting that LPS causes activated fatty acids to undergo esterification and lipogenesis rather than oxidation. Treatment of rats with L-carnitine before LPS greatly increased the survival rate, but did not affect enzymes that metabolize fatty acids, CoA, or carnitine derivatives in the liver. Further studies are necessary to elucidate the mechanism of the effect of carnitine on post-LPS survival.
Assuntos
Carnitina/farmacologia , Ácidos Graxos/metabolismo , Fígado/metabolismo , Proteínas Repressoras , Proteínas de Saccharomyces cerevisiae , Choque Séptico/metabolismo , Animais , Carnitina/metabolismo , Carnitina O-Acetiltransferase/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Coenzima A/metabolismo , Coenzima A Ligases/metabolismo , Escherichia coli , Esterificação , Corpos Cetônicos/metabolismo , Lipopolissacarídeos , Fígado/efeitos dos fármacos , Masculino , Malonil Coenzima A/metabolismo , Oxirredução , Ratos , Ratos EndogâmicosRESUMO
Cecal ligation and puncture (CLP) were performed in rats. After 4 hr (early sepsis) and 16 hr (late sepsis), platelet morphology and function were studied. At 16 hr, platelet counts for the CLP group were significantly lower than for the sham-operated control group. Low maximum aggregation rates (MAR) and decreased platelet counts were elicited in platelet-rich plasma with 4 M ADP and 2 micrograms/ml collagen. However, with platelet counts equalized, MAR for the CLP group increased significantly, especially after 16 hr. The platelet-large cell rate and platelet distribution width decreased temporarily at 4 hr, then rose significantly at 16 hr. No significant changes were observed in the mean platelet volume after 4 hr, but there were significant increases after 16 hr. Total adenine nucleotide (TAN) levels within the platelets rose significantly in the CLP group, suggesting the appearance during the late sepsis of large, heavy platelets or adenine nucleotide-rich platelets. The platelet adenylate pool was divided into granular and cytoplasmic fractions, respectively characterized by ADP and ATP increases. However, no septicemia-related differences were noted in the degree of binding between goat antirat fibrinogen and platelet surface glycoprotein IIb/IIIa complex. Internal environment changes in the platelets indicated that during septicemia hyperfunctional or hypersensitive platelets with a latent capacity for active aggregation and release appeared in the circulation. Hypercoagulability in septicemia involves activation of coagulation factors, stimulation of the coagulation cascade, volume changes accompanying increased platelet TAN content, and changes in AN distribution in the two pools. These findings significantly increase our understanding of the transition from the prethrombotic state to thrombosis in septicemia.