RESUMEN
BACKGROUND: Giant Prostate (more than 100 g) is rare worldwide but Common in Africa. However Giant Median Lobe Enlargement is rare even in Africa. This Uncommon entity may pose a diagnostic puzzle especially when associated with haematuria, necroturia and suprapubic mass with background history of childhood haematuria. OBJECTIVE: To present a rare case of a giant benign median lobe enlargement of the prostate. METHODS: A 75 year old retired police officer presenting with 18 months history of intermittent total Painless hematuria, necroturia, increased frequency and feeling of incomplete bladder emptying. There was hesitancy and difficulty in passing Urine improved by manual pressure on the lower abdomen by the patient. Patient was evaluated clinically, radiologically, and also had Urine Cytology suggestive of malignancy. Cystoscopy and Biopsy revealed Inflammation. Patient sought medical Treatment in several hospitals and finally referred to our hospital. RESULTS: He was found to be clinically preserved, not pale, with a mobile suprapubic mass of about 12 cm above pubic symphysis,. Digital Rectal Examination revealed prostate not enlarged. Abdomino-Pelvic ultrasound scan, Intravenous Urography, and Urethrocystography all suggested a huge bladder Tumour at the base occupying almost half of the bladder. Patient was prepared for Cystectomy and Urinary diversion. However, intra-operative finding revealed a giant median lobe enlargement of the prostate (225 g) with normal lateral Lobes, no other bladder mass seen. Transvesical prostatectomy was carried out. Patient did well postoperatively and was discharged. CONCLUSION: Giant Median Lobe Enlargement of the Prostate is rare and may present with hematuria, necroturia and supra pubic mass with normal digital rectal examination.
Asunto(s)
Hiperplasia Prostática/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Anciano , Diagnóstico Diferencial , Humanos , Masculino , Hiperplasia Prostática/cirugíaRESUMEN
BACKGROUND: To determine the pharmacokinetics (PK) of a new i.v. formulation of paracetamol (Perfalgan) in children ≤15 yr of age. METHODS: After obtaining written informed consent, children under 16 yr of age were recruited to this study. Blood samples were obtained at 0, 15, 30 min, 1, 2, 4, 6, and 8 h after administration of a weight-dependent dose of i.v. paracetamol. Paracetamol concentration was measured using a validated high-performance liquid chromatographic assay with ultraviolet detection method, with a lower limit of quantification (LLOQ) of 900 pg on column and an intra-day coefficient of variation of 14.3% at the LLOQ. Population PK analysis was performed by non-linear mixed-effect modelling using NONMEM. RESULTS: One hundred and fifty-nine blood samples from 33 children aged 1.8-15 yr, weight 13.7-56 kg, were analysed. Data were best described by a two-compartment model. Only body weight as a covariate significantly improved the goodness of fit of the model. The final population models for paracetamol clearance (CL), V(1) (central volume of distribution), Q (inter-compartmental clearance), and V(2) (peripheral volume of distribution) were: 16.51×(WT/70)(0.75), 28.4×(WT/70), 11.32×(WT/70)(0.75), and 13.26×(WT/70), respectively (CL, Q in litres per hour, WT in kilograms, and V(1) and V(2) in litres). CONCLUSIONS: In children aged 1.8-15 yr, the PK parameters for i.v. paracetamol were not influenced directly by age but were by total body weight and, using allometric size scaling, significantly affected the clearances (CL, Q) and volumes of distribution (V(1), V(2)).
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Acetaminofén/sangre , Analgésicos no Narcóticos/sangre , Acetaminofén/administración & dosificación , Acetaminofén/uso terapéutico , Adolescente , Envejecimiento/sangre , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/uso terapéutico , Anestesia General , Recolección de Muestras de Sangre/métodos , Peso Corporal/fisiología , Niño , Preescolar , Cromatografía Líquida de Alta Presión/métodos , Esquema de Medicación , Femenino , Humanos , Lactante , Inyecciones Intravenosas , Masculino , Modelos Biológicos , Dolor Postoperatorio/prevención & controlRESUMEN
There are considerable differences in the plasma lipid profile between lean and obese individuals and between men and women. Little, however, is known regarding the effects of obesity and sex on the plasma concentration of enzymes involved in intravascular lipid remodeling. Therefore, we measured the immunoreactive protein mass of lipoprotein lipase (LPL), hepatic lipase (HL), cholesterol-ester transfer protein (CETP) and lecithin-cholesterol acyl transferase (LCAT) in fasting plasma samples from 40 lean and 40 obese non-diabetic men and premenopausal women. Women, compared with men, had approximately 5% lower plasma LCAT (p < 0.041), approximately 35% greater LPL (p = 0.001) and approximately 10% greater CETP (p = 0.085) concentrations. Obese, compared with lean individuals of both sexes, had approximately 30% greater plasma LCAT (p < 0.001), approximately 20% greater CETP (p < 0.001) and approximately 20% greater LPL (p = 0.071) concentrations. Plasma HL concentration was not different in lean men and women. Obesity was associated with increased (by approximately 50%) plasma HL concentration in men (p = 0.018) but not in women; consequently, plasma HL concentration was lower in obese women than obese men (p = 0.009). In addition, there were direct correlations between plasma lipid transfer enzyme concentrations and lipoprotein particle concentrations and sizes. There are considerable differences in basal plasma lipid transfer enzyme concentrations between lean and obese subjects and between men and women, which may be partly responsible for respective differences in the plasma lipid profile.
Asunto(s)
Enzimas/sangre , Obesidad/enzimología , Delgadez/enzimología , Proteínas de Transferencia de Ésteres de Colesterol/sangre , Femenino , Humanos , Lipasa/sangre , Metabolismo de los Lípidos , Lipoproteína Lipasa/sangre , Masculino , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Factores SexualesRESUMEN
OBJECTIVE: To determine the effect of obesity without the confounding effect of metabolic complications on the lipoprotein subclass profile in men and women. DESIGN: Cross-sectional study. SUBJECTS: A total of 40 lean (body mass index (BMI): 18.5-25 kg/m(2)) and 40 obese (BMI: 30-45 kg/m(2)) subjects, with blood pressure <140/90 mm Hg, fasting plasma glucose concentration <100 mg per 100 ml and total triglyceride concentration <150 mg per 100 ml; all obese subjects had normal oral glucose tolerance. MEASUREMENTS: Fasting concentrations of very low-, intermediate-, low- and high-density lipoproteins (VLDL, IDL, LDL, and HDL, respectively) and average VLDL, LDL and HDL particle sizes were evaluated by using proton nuclear magnetic resonance spectroscopy. RESULTS: Obese compared with lean individuals of both sexes had increased plasma concentrations of VLDL (by approximately 50%), IDL (by approximately 100%), LDL (by approximately 50%), and to some extent HDL (by approximately 10%) particles (P<0.05). The contribution of large VLDL to total VLDL concentration, small LDL to total LDL concentration, and small HDL to total HDL concentration was greater in obese than lean subjects (P<0.05), resulting in larger average VLDL size but smaller average LDL and HDL sizes (P<0.05). Women, compared with men, had reduced concentrations of total VLDL particles (by approximately 10%) due to lower concentrations of large and medium VLDL and a shift toward large at the expense of small HDL particles (P<0.05), with no difference in total HDL particle concentration. IDL and total LDL concentrations and LDL subclass distribution were not different between men and women. CONCLUSION: Obesity is associated with pro-atherogenic alterations in the lipoprotein subclass profile, which may increase cardiovascular disease risk even in the absence of classical metabolic risk factors. On the other hand, the female cardiovascular disease risk advantage is probably largely related to differences in traditional lipid risk factors (plasma triglyceride and HDL-cholesterol concentrations) because sex differences in the plasma lipoprotein subclass profile are minimal.
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Glucemia/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Lipoproteínas/sangre , Obesidad/sangre , Adolescente , Adulto , Análisis de Varianza , Índice de Masa Corporal , Enfermedad de la Arteria Coronaria/prevención & control , Estudios Transversales , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , Factores de Riesgo , Factores Sexuales , Triglicéridos/sangre , Adulto JovenRESUMEN
We examined rejection outcome and graft survival in 58 adult patients with acute cellular rejection Banff type I (ARI) or II (ARII), within 1 year after transplantation, with or without CD20-positive infiltrates. Antibody-mediated rejection was not examined. Of the 74 allograft biopsies, performed from 1999 to 2001, 40 biopsies showed ARI and 34 biopsies showed ARII; 30% of all the biopsies showed CD20-positive clusters with more than 100 cells, 9% with more than 200 cells and 5% with more than 275 cells. Patients with B cell-rich (>100 or >200/HPF CD20-positive cells) and B cell-poor biopsies (<50 CD20-positive cells/HPF) were compared. Serum creatinine and eGFR of B cell-rich (CD20 > 100/HPF) and B cell-poor were not significantly different at rejection, or at 1, 3, 6 and 12 months, and during additional 3 years follow-up after rejection, although higher creatinine at 1 year was noted in the >200/HPF group. Graft survival was also not different between B cell-rich and B cell-poor groups (p = 0.8 for >100/HPF, p = 0.9 for >200/HPF CD20-positive cells). Our data do not support association of B cell-rich infiltrates in allograft biopsies and worse outcome in acute rejection type I or II, but do not exclude the possible contribution of B cells to allograft rejection.
Asunto(s)
Antígenos CD20/inmunología , Rechazo de Injerto/patología , Supervivencia de Injerto/inmunología , Trasplante de Riñón/inmunología , Enfermedad Aguda , Adulto , Anciano , Linfocitos B/inmunología , Linfocitos B/patología , Creatinina/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/sangre , Rechazo de Injerto/inmunología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
The prevalence of Sarcocystis spp. infection was investigated in 605 sheep, 826 goats, 1080 cattle, 580 water buffaloes and 36 camels slaughtered from 1992 to 1996 in the Baghdad area (Iraq) using naked eye examination for macroscopic sarcocysts, and peptic digestion, muscle squash, squeezing methods and indirect fluorescent antibody test (IFAT) for microscopic types. The intestinal stages of the parasite were also studied in dogs experimentally fed with tissues containing microscopic cysts. The percentage prevalence of macroscopic cysts were 4.1, 33.6, 0.2, 15.6 and 0, and of the microscopic type, 97.0, 97.4, 97.8, 82.9 and 91.6 for the above-mentioned hosts, respectively. Among the different organs examined, macroscopic cysts were found to be highest in the oesophagus and the lowest in the heart. Peptic digestion method gave the highest rate (93.3%) followed by indirect fluorescent antibody test (IFAT) (88.6%), squeezing (81.3%), and muscle squash (81.2%). Each infected dog shed a total of about 150-200 million sporocysts. Histologically, developmental stages of the parasite were detected in the small intestinal mucosa of the dogs on Days 7 and 13 post-infection.
Asunto(s)
Búfalos , Camelus , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Perros/epidemiología , Enfermedades de las Cabras/epidemiología , Sarcocystis/aislamiento & purificación , Sarcocistosis/veterinaria , Enfermedades de las Ovejas/epidemiología , Animales , Bovinos , Enfermedades de los Bovinos/parasitología , Diafragma/parasitología , Enfermedades de los Perros/parasitología , Perros , Esófago/parasitología , Heces/parasitología , Técnica del Anticuerpo Fluorescente Indirecta/veterinaria , Enfermedades de las Cabras/parasitología , Cabras , Corazón/parasitología , Enfermedades Intestinales/epidemiología , Enfermedades Intestinales/veterinaria , Irak/epidemiología , Carne/parasitología , Músculo Esquelético/parasitología , Recuento de Huevos de Parásitos/veterinaria , Pepsina A/química , Prevalencia , Sarcocistosis/epidemiología , Ovinos , Enfermedades de las Ovejas/parasitologíaRESUMEN
It is now established that fatty acid 7,10,13,16-22:4 is metabolized into 4,7,10,13,16-22:5 as follows: 7,10,13,16-22:4-->9,12,15, 18-24:4-->6,9,12,15,18-24:5-->4,7,10,13,16-22:5. Neither C24 fatty acid was esterified to 1-acyl-sn-glycero-3-phosphocholine (1-acyl-GPC) by microsomes, whereas the rates of esterification of 4, 7,10,13,16-22:5, 7,10,13,16-22:4 and 5,8,11,14-20:4 were respectively 135, 18 and 160 nmol/min per mg of microsomal protein. About four times as much acid-soluble radioactivity was produced when peroxisomes were incubated with [3-14C]9,12,15,18-24:4 compared with 6,9,12,15,18-24:5. Only [1-14C]7,10,13,16-22:4 accumulated when [3-14C]9,12,15,18-24:4 was the substrate, but both 4,7,10,13,16-22:5 and 2-trans-4,7,10,13,16-22:6 were produced from [3-14C]6,9,12,15, 18-24:5. When the two C24 fatty acids were incubated with peroxisomes, microsomes and 1-acyl-GPC there was a decrease in the production of acid-soluble radioactivity from [3-14C]6,9,12,15, 18-24:5, but not from [3-14C]9,12,15,18-24:4. The preferential fate of [1-14C]4,7,10,13,16-22:5, when it was produced, was to move out of peroxisomes for esterification into the acceptor, whereas only small amounts of 7,10,13,16-22:4 were esterified. By using 2H-labelled 9,12,15,18-24:4 it was shown that, when 7,10,13,16-22:4 was produced, its primary metabolic fate was degradation to yield esterified arachidonate. Collectively, the results show that an inverse relationship exists between rates of peroxisomal beta-oxidation and of esterification into 1-acyl-GPC by microsomes. Most importantly, when a fatty acid is produced with its first double bond at position 4, it preferentially moves out of peroxisomes for esterification to 1-acyl-GPC by microsomes, rather than being degraded further via a cycle of beta-oxidation that requires NADPH-dependent 2,4-dienoyl-CoA reductase.
Asunto(s)
Ácidos Grasos Insaturados/biosíntesis , Microsomas Hepáticos/metabolismo , Acilación , Animales , Unión Competitiva , Esterificación , Ácidos Grasos/metabolismo , Ácidos Grasos Omega-3 , Ácidos Grasos Insaturados/metabolismo , Ácidos Grasos Volátiles/metabolismo , Masculino , Microcuerpos/metabolismo , Oxidación-Reducción , Fosforilcolina/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
The synthesis of 4,7,10,13,16,19-docosahexaenoic acid (22:6(n-3)) requires that when 6,9,12,15,18,21-tetracosahexaenoic acid (24:6(n-3)) is produced in the endoplasmic reticulum, it preferentially moves to peroxisomes for one cycle of beta-oxidation rather than serving as a substrate for membrane lipid synthesis. Both 24:6(n-3) and its precursor, 9,12,15,18,21-tetracosapentaenoic acid (24:5(n-3)), were poor substrates for acylation into 1-acyl-sn-glycero-3-phosphocholine (1-acyl-GPC) by rat liver microsomes. When peroxisomes were incubated with 1-14C- or 3-14C-labeled 7,10,13,16,19-docosapentaenoic acid (22:5(n-3)), [1-14C]22:6(n-3), [3-14C]24:5(n-3), or [3-14C]24:6(n-3), only small amounts of acid-soluble radioactivity were produced when double bond removal at positions 4 and 5 was required. When microsomes and 1-acyl-GPC were included in incubations, the preferred metabolic fate of acids, with their first double bond at either positions 4 or 5, was to move out of peroxisomes for esterification into the acceptor rather than serving as substrates for continued beta-oxidation. When [1-14C]22:6(n-3) or [3-14C]24:6(n-3) was incubated with peroxisomes, 2-trans-4,7,10,13,16,19-22:7 accumulated. The first cycle of 20:5(n-3) beta-oxidation proceeds through 2-trans-4,8,11,14,17-20:6 and thus requires both Delta3,5,Delta2, 4-dienoyl-CoA isomerase and 2,4-dienoyl-CoA reductase. The accumulation of the substrate for 2,4-dienoyl-CoA reductase, as generated from 22:6(n-3), but not from 20:5(n-3), suggests that this enzyme distinguishes between subtle structural differences. When 22:6(n-3) is produced from 24:6(n-3), its continued degradation is impaired because of low 2,4-dienoyl-CoA reductase activity. This slow reaction rate likely contributes to the transport of 22:6(n-3) out of peroxisomes for rapid acylation into 1-acyl-GPC by microsomes.
Asunto(s)
Clofibrato/farmacología , Ácidos Docosahexaenoicos/metabolismo , Hígado/metabolismo , Microcuerpos/metabolismo , Microsomas Hepáticos/metabolismo , Acilcoenzima A/metabolismo , Animales , Radioisótopos de Carbono , Cromatografía Líquida de Alta Presión , Dieta , Ácidos Docosahexaenoicos/aislamiento & purificación , Retículo Endoplásmico/metabolismo , Cinética , Hígado/efectos de los fármacos , Masculino , Lípidos de la Membrana/aislamiento & purificación , Lípidos de la Membrana/metabolismo , Modelos Biológicos , Oxidación-Reducción , Técnica de Dilución de Radioisótopos , Ratas , Ratas Sprague-DawleyRESUMEN
Recent studies refute the commonly accepted, but untested, hypothesis that 7,10,13,16-22:4 and 7,10,13,16,19-22:5 are desaturated at position 4 by a microsomal acyl-CoA-dependent desaturase. The synthesis of 4,7,10,13,16,19-22:6 occurs via the following reaction sequence: 7,10,13,16,19-22:5-->9,12,15,18,21-24:5-->6,9,12,15,18,21-24:6 4,7,10,13,16,19-22:6. The synthesis of 4,7,10,13,16-22:5 from 7,10,13,16-22:4 takes place via an analogous pathway. According to these pathways the 24-carbon acids that are made in the endoplasmic reticulum move to a site for partial beta-oxidation, which is most likely peroxisomes. The products of partial beta-oxidation, 4,7,10,13,16-22:5 and 4,7,10,13,16,19-22:6, then move back to the endoplasmic reticulum where they are used as substrates for membrane lipid biosynthesis. The ability of a fatty acid to serve as a substrate for continued peroxisomal beta-oxidation, versus its transfer out of peroxisomes for subsequent endoplasmic reticulum-associated esterification reactions, may be an important control for regulating membrane lipid fatty acid composition. Indeed, the revised pathways of polyunsaturated fatty acid biosynthesis imply that there is considerable intracellular movement and recycling of fatty acids between peroxisomes and the endoplasmic reticulum. In addition, these revised pathways require that two 18-carbon and two 24-carbon acids are substrates for desaturation at position 6. Also, as linoleate and linolenate are metabolized, respectively, to 6,9,12,15,18-24:5 and 6,9,12,15,18,21-24:6, three n-6 acids and three n-3 acids are substrates for malonyl-CoA dependent chain elongation. It remains to be determined how many microsomal enzymes are required to carry out these reactions and whether other ancillary enzymes are expressed in tissues whose membrane lipids accumulate very long-chain polyunsaturated acids with up to 36 carbon atoms.
Asunto(s)
Ácidos Grasos Insaturados/biosíntesis , Acil-CoA Deshidrogenasa de Cadena Larga/metabolismo , Animales , Humanos , Microcuerpos/metabolismo , Oxidación-ReducciónAsunto(s)
Ácidos Grasos Insaturados/biosíntesis , Animales , Ácido Araquidónico/biosíntesis , Grasas de la Dieta/metabolismo , Ácido Eicosapentaenoico/biosíntesis , Retículo Endoplásmico/enzimología , Grasas Insaturadas/metabolismo , Masculino , Lípidos de la Membrana/biosíntesis , Modelos Biológicos , Ratas , Ratas Sprague-DawleyRESUMEN
When rat liver microsomes were incubated with [1-14C]22:4(n-6) under standard conditions for measuring acyl-CoA desaturases, it was not possible to detect the synthesis of any 22:5(n-6). When malonyl-CoA and NADPH were included in the incubation, 22:4(n-6) was chain elongated to 24:4(n-6), which was then desaturated to 24:5(n-6). Rat hepatocytes metabolized [1-14C]22:4(n-6), [3-14C]24:4(n-6), and [3-14C]24:5(n-6) to yield esterified radioactive 22:5(n-6). The results show that 22:4(n-6) is the precursor of 22:5(n-6) but the pathway is independent of an acyl-CoA-dependent 4-desaturase and probably requires intracellular communication between the endoplasmic reticulum and a site for beta-oxidation. Microsomal reaction rates for (n-6) versus (n-3) polyunsaturated fatty acid biosynthesis cannot per se be used to explain why in vivo most membrane lipids preferentially accumulate 22:6(n-3) rather than 22:5(n-6). Rates of desaturation of 24:4(n-6) and 24:5(n-3) at position 6 were similar (M. Geiger et al., Biochim. Biophys. Acta 1170, 137-142, 1993). We now show that 20:4(n-6) and 20:5(n-3) are chain elongated at the same rate as are 22:4(n-6) and 22:5(n-3). At present, no single reaction can be defined as being substrate specific or rate limiting to explain why there is an apparent selective synthesis and acylation of 22:6(n-3) rather than 22:5(n-6) into membrane lipids.
Asunto(s)
Ácidos Erucicos/metabolismo , Ácidos Grasos Insaturados/metabolismo , Microsomas Hepáticos/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Masculino , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Especificidad por SustratoRESUMEN
According to the revised pathway for 22:6(n - 3) biosynthesis in liver (Voss et al. (1991) J. Biol. Chem. 266, 19995-20000) both 18:3(n - 3) and 24:5(n - 3) serve as substrates for desaturation at position-6. The present study was undertaken to determine whether microsomes contain chain-length-specific 6-desaturases. Addition of [1-14C]20:3(n - 6), a substrate for desaturation at position-5, did not depress desaturation of either [1-14C]18:3(n - 3) or [3-14C]24:5(n - 3). An unexplained observation was that both 18:3(n - 3) and 24:5(n - 3) inhibited the metabolism of 20:3(n - 6) to 20:4(n - 6). When an enzyme-saturating level of [3-14C]24:5(n - 3) was now incubated alone and with 40, 80 and 120 nmol of [1-14C]18:3(n - 3), the production of 24:6(n - 3) was inhibited by 43, 67 and 81%. Conversely, when [1-14C]18:3(n - 3) was incubated with 40, 80 or 120 nmol of [3-14C]24:5(n - 3), the synthesis of 18:4(n - 3) was inhibited by only 15, 20 and 27%. These and other competitive studies showed that there was always preferential desaturation of 18:3(n - 3) rather than 24:5(n - 3). In addition, competitive studies between 18:2(n - 6) and 18:3(n - 3), as well as with 24:4(n - 6) and 24:5(n - 3) showed that there was always preferential desaturation of the (n - 3) acid. Although our results are consistent with a single 6-desaturase, further studies, including the isolation of the 6-desaturases(s), is obviously required to determine whether multiple forms of the 6-desaturase exist.
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Ácido Graso Desaturasas/análisis , Ácidos Grasos Insaturados/biosíntesis , Microsomas Hepáticos/enzimología , Animales , Radioisótopos de Carbono , Grasas de la Dieta/administración & dosificación , Masculino , Lípidos de la Membrana/biosíntesis , Ratas , Ratas Sprague-Dawley , Especificidad por SustratoRESUMEN
When rats were fed 5% corn oil, the heart phospholipids contained large amounts of 22-carbon (n-6) acids. When half of the corn oil was replaced with fish oil, the reduced level of arachidonate and 22-carbon (n-6) acids in phospholipids was accompanied by increases in the levels of 22-carbon (n-3) acids while only small amounts of 20:5(n-3) were acylated. Heart myocytes readily took up and acylated [1-14C]-labeled 20:4(n-6), 20:5(n-3) and 22:6(n-3) into phospholipids. The uptake and acylation of 20:4(n-6) was greater than for 20:5(n-3) but the intracellular labeling profiles were similar. Uptake and acylation of 22:6(n-3) was somewhat lower. In addition the intracellular labeling profile differed in that more 22:6(n-3) was incorporated into the ethanolamine-containing phospholipids than when 20:4(n-6) or 20:5(n-3) were the substrates. Neither 20:4(n-6) nor 20:5(n-3) was chain elongated. When [3-14C]-labeled 22:4(n-6) and 22:5(n-3) were the substrates, it was not possible to detect radioactive 22:5(n-6) or 22:6(n-3). Both [3-14]-labeled substrates were acylated into phospholipids and retroconverted with the subsequent esterification of radioactive 20:4(n-6) and 20:5(n-3) into triglycerides and phospholipids. These studies show that cardiomyocytes lack the ability to make 22-carbon acids from 20-carbon precursors but they retroconvert 22-carbon acids to 20-carbon acids. The high levels of 22-carbon polyunsaturated acids in total heart lipids thus cannot be attributed to the synthetic capacities of cardiomyocytes.
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Ácidos Grasos Insaturados/metabolismo , Aceites de Pescado/administración & dosificación , Músculos/metabolismo , Miocardio/metabolismo , Animales , Ácido Araquidónico , Ácidos Araquidónicos/metabolismo , Peces , Técnicas In Vitro , Masculino , Músculos/citología , Miocardio/citología , Fosfolípidos/metabolismo , Ratas , Ratas Endogámicas , Triglicéridos/metabolismoRESUMEN
Several inherited disorders of fatty acid beta-oxidation have been described that relate mainly to saturated precursors. This study is the first report of an enzyme defect related only to unsaturated fatty acid oxidation and provides the first in vivo evidence that fat oxidation in humans proceeds by the reductase-dependent pathway. The patient was a black female, presenting in the neonatal period with persistent hypotonia. Biochemical studies revealed hyperlysinemia, hypocarnitinemia, normal organic acid profile, and an unusual acylcarnitine species in both urine and blood. The new metabolite was positively identified by mass spectrometry as 2-trans,4-cis-decadienoylcarnitine, derived from incomplete oxidation of linoleic acid. In spite of dietary therapy, the patient died of respiratory acidosis at four months of age. Samples of liver and muscle from the autopsy were assayed for 2,4-dienoyl-coenzyme A reductase activity. Using the substrate 2-trans,4-cis-decadienoylcoenzyme A, the reductase activity was 40% of the control value in liver and only 17% of that found in normal muscle. It is suggested that unsaturated substrates should be used for in vitro testing to cover the full range of potential beta-oxidation defects and that acylcarnitine species identification be used for in vivo detection of this disorder.
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Ácido Graso Desaturasas/deficiencia , Ácidos Grasos no Esterificados/sangre , Errores Innatos del Metabolismo Lipídico/enzimología , Hígado/enzimología , Músculos/enzimología , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Ácido Graso Desaturasas/metabolismo , Ácidos Grasos no Esterificados/orina , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Ácido Linoleico , Ácidos Linoleicos/metabolismo , Valores de ReferenciaRESUMEN
Salicylates are metabolized in vivo to hydroxylated compounds, including 2,3-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid (gentisic acid). The present study hypothesized that activated neutrophils represent one pathway for salicylate hydroxylation. Human neutrophils were incubated in medium containing 10 mM salicylate and stimulated with phorbol myristate acetate (PMA) for 1 hr. The cell-free supernatant fractions were analyzed by HPLC. Neutrophils (1 x 10(6) cells) produced 55 +/- 11 ng of gentisic acid. Neutrophils also produced smaller quantities of 2,3-dihydroxybenzoic acid. Antioxidant inhibitor experiments indicated that superoxide dismutase (SOD), heme protein inhibitors, and glutathione blocked gentisic acid formation, whereas catalase, mannitol, and deferoxamine failed to inhibit. Experiments with the reagent hypochlorous acid (HOCl) and the model myeloperoxidase (MPO) enzyme system did not support a role for the MPO pathway in gentisic acid formation. These findings demonstrate that activated neutrophils can hydroxylate salicylate by an unknown pathway. This pathway may contribute to the increased recovery of hydroxylated salicylates in patients with inflammatory disorders.
Asunto(s)
Gentisatos , Neutrófilos/metabolismo , Salicilatos/sangre , Amitrol (Herbicida)/farmacología , Azidas/farmacología , Cromatografía Líquida de Alta Presión , Cianuros/farmacología , Glutatión/farmacología , Humanos , Hidroxibenzoatos/sangre , Hidroxilación , Neutrófilos/efectos de los fármacos , Peroxidasa/sangre , Ácido Salicílico , Superóxido Dismutasa/farmacología , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
Eosinophils exhibit different levels of oxidative metabolism depending on their site of origin and various host factors that may influence metabolism. The present study examined the time course of eosinophil oxidative metabolism in animals undergoing chronic peritoneal stimulation. Eosinophils were purified from the peritoneal exudates of guinea pigs stimulated with weekly polymyxin B and saline peritoneal lavage. 14C-1- and 14C-6-glucose oxidation and H2O2 production were measured at week 0 and at various time points throughout 43 weeks of stimulation. Baseline oxidative metabolism of eosinophils was relatively high throughout the time course, but then declined sharply after 32 weeks. These "deactivated" cells that were recovered after 32 weeks also failed to respond to phorbol myristate acetate (PMA) or opsonized zymosan. Electron microscopy did not reveal significant differences between deactivated eosinophils and cells from earlier time points. These findings document the time course of eosinophil activation and deactivation in this model and suggest that metabolic heterogeneity of eosinophils can occur over time in response to a chronic stimulus.
Asunto(s)
Eosinófilos/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Polimixina B/administración & dosificación , Polimixinas/administración & dosificación , Animales , Esquema de Medicación , Eosinófilos/metabolismo , Eosinófilos/ultraestructura , Femenino , Cobayas , Recuento de Leucocitos/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Cavidad Peritoneal , Acetato de TetradecanoilforbolRESUMEN
The neutrophil myeloperoxidase-H2O2-halide enzyme system produces hypochlorous acid and chlorinated amine compounds capable of killing a variety of target cells. In the present study we hypothesized that the myeloperoxidase enzyme system is one mechanism for airway epithelial damage in patients with cystic fibrosis (CF). Enzyme linked immunosorbent assay detected high antigenic levels of myeloperoxidase in sputum samples of seven patients with CF. Myeloperoxidase was purified to homogeneity from CF sputum and from blood neutrophils by a three-step technique involving dialysis, gel filtration, and ion-exchange chromatography. CF sputum myeloperoxidase and neutrophil myeloperoxidase appeared identical by acid gel electrophoresis and Ouchterlony experiments. CF sputum myeloperoxidase also contained approximately the same enzymatic activity as neutrophil myeloperoxidase. The myeloperoxidase enzyme system was tested for its cytotoxic potential in a tracheal ring culture system. Myeloperoxidase-induced cytotoxicity for airway epithelium was confirmed by light microscopy and radiolabelling experiments. These findings suggest a possible role for neutrophil myeloperoxidase in CF lung disease.