Accuracy of heparin binding protein: as a new marker in prediction of acute bacterial meningitis

ABSTRACT Background: Cerebrospinal fluid bacterial culture is the gold-standard for confirmation of acute bacterial meningitis, but many cases are not culture confirmed. Antibiotics reduce the chance of a microbiological diagnosis. Objective to evaluate efficacy of Heparin-binding protein in diagnosis of bacterial meningitis. Patients: 30 patients diagnosed with acute bacterial meningitis, 30 viral meningitis, and 30 subjects with normal CSF findings. Design: Diagnosis was based on history, clinical criteria, CSF examination, latex agglutination & culture, and sensitivities and response to therapy. HBP was measured using enzyme-linked immunosorbent technique in both serum & CSF. Results: Cerebrospinal fluid HBP levels averaged 0.82 ± 0.3 ng/mL in controls, 3.3 ± 1.7 ng/mL in viral and 174.8 ± 46.7 ng/mL in bacterial meningitis. Mean serum level was 0.84 ± 0.3 ng/mL in the controls, 3.7 ± 1.9 ng/mL in viral, and 192.2 ± 56.6 ng/mL in bacterial meningitis. Both HBP levels were significantly higher in patients with bacterial meningitis. Cut-offs of 56.7 ng/ml and 45.3 ng/ml in cerebrospinal fluid & serum showed 100% overall accuracy. Even in patients who received prior antibiotics, remained elevated. Conclusion: Serum Heparin-binding protein serves as a non-invasive potential marker of acute bacterial meningitis even in partially treated cases.

Reversible flow of cholesteryl ester between high-density lipoproteins and triacylglycerol-rich particles is modulated by the fatty acid composition and concentration of triacylglycerols

We determined the influence of fasting (FAST) and feeding (FED) on cholesteryl ester (CE) flow between high-density lipoproteins (HDL) and plasma apoB-lipoprotein and triacylglycerol (TG)-rich emulsions (EM) prepared with TG-fatty acids (FAs). TG-FAs of varying chain lengths and degrees of unsaturation were tested in the presence of a plasma fraction at d > 1.21 g/mL as the source of CE transfer protein. The transfer of CE from HDL to FED was greater than to FAST TG-rich acceptor lipoproteins, 18 percent and 14 percent, respectively. However, percent CE transfer from HDL to apoB-containing lipoproteins was similar for FED and FAST HDL. The CE transfer from HDL to EM depended on the EM TG-FA chain length. Furthermore, the chain length of the monounsaturated TG-containing EM showed a significant positive correlation of the CE transfer from HDL to EM (r = 0.81, P < 0.0001) and a negative correlation from EM to HDL (r = -041, P = 0.0088). Regarding the degree of EM TG-FAs unsaturation, among EMs containing C18, the CE transfer was lower from HDL to C18:2 compared to C18:1 and C18:3, 17.7 percent, 20.7 percent, and 20 percent, respectively. However, the CE transfer from EMs to HDL was higher to C18:2 than to C18:1 and C18:3, 83.7 percent, 51.2 percent, and 46.3 percent, respectively. Thus, the EM FA composition was found to be the rate-limiting factor regulating the transfer of CE from HDL. Consequently, the net transfer of CE between HDL and TG-rich particles depends on the specific arrangement of the TG acyl chains in the lipoprotein particle core.

Novel nonsense mutation (p. Y113X) in the human growth hormone receptor gene in a Brazilian patient with Laron syndrome / Nova mutação nonsense (p. Y113X) no gene do receptor do hormônio do crescimento em um paciente brasileiro com síndrome de Laron

BACKGROUND: To date, about sixty different mutations within GH receptor (GHR) gene have been described in patients with GH insensitivity syndrome (GHI). In this report, we described a novel nonsense mutation of GHR. METHODS: The patient was evaluated at the age of 6 yr, for short stature associated to clinical phenotype of GHI. GH, IGF-1, and GHBP levels were determined. The PCR products from exons 2-10 were sequenced. RESULTS: The patient had high GH (26 µg/L), low IGF-1 (22.5 ng/ml) and undetectable GHBP levels. The sequencing of GHR exon 5 disclosed adenine duplication at nucleotide 338 of GHR coding sequence (c.338dupA) in homozygous state. CONCLUSION: We described a novel mutation that causes a truncated GHR and a loss of receptor function due to the lack of amino acids comprising the transmembrane and intracellular regions of GHR protein, leading to GHI.

INTRODUÇÃO: Até o momento, aproximadamente 60 diferentes mutações envolvendo o gene do receptor do GH (GHR) foram descritas em pacientes com a síndrome de insensibilidade ao GH (GHI). Neste artigo, descrevemos uma nova mutação nonsense do GHR. MÉTODOS: O paciente foi avaliado aos 6 anos de idade para baixa estatura associada ao fenótipo clínico da GHI. Níveis de GH, IGF-1 e GHBP foram determinados. Os produtos de PCR dos éxons 2-10 foram seqüenciados. RESULTADOS: O paciente apresentou níveis elevados de GH (26 µg/L), baixos de IGF-1 (22.5 ng/ml) e indetectáveis de GHBP. O seqüenciamento do éxon 5 do GHR revelou uma duplicação da adenina no nucleotídeo 338 da sequência de codificação do GHR (c.338dupA) em homozigose. CONCLUSÃO: Descrevemos uma nova mutação que causa um GHR truncado e uma perda da função do receptor devido à perda de aminoácidos compreendendo as regiões transmembrana e intracelular do receptor, levando a GHI.

Proteína ligadora de ácidos grasos de miocito: marcador precoz de infarto agudo al miocardio / Myoccityc fatty acid-binding protein: early markers in acute myocardial infarction

La cardiopatía coronaria es la primera causa de muerte en Chile y el infarto agudo del miocardio una de las patologías con garantías explícitas recientemente implementadas, exigiendo un diagnóstico precoz (30 minutos desde el momento de la consulta). Las troponinas e isoformas mb de la creatinfosfoquinasa son marcadores tardíos de daño miocárdico. La proteína ligadora de ácidos grasos de miocito (h-FABP), proteína citosólica del citoesqueleto miocárdico, es un marcador precoz de necrosis miocárdica detectándose ya a los 30 minutos de la injuria. Objetivo: Determinar la presencia temprana de h-FABP en síndrome coronario agudo (SCA) con supradesnivel del segmento ST (SDST) y su correlación tardía con diagnóstico infarto agudo del miocardio (IM). Materiales y métodos: Se reclutó a pacientes con SCA SDST con <6 horas de inicio de sus síntomas entre el 1/8/04 al 6/9/05 en el Servicio de Urgencias del Hospital del Salvador. Con registro de antecedentes personales, clínicos, electrocardiográficos, troponinas y/o CPK mb. Se correlacionó h-FABP (test rápido inmunoensayo de anticuerpos monoclonales, cualitativo (Cardiodetect®)) con diagnóstico confirmado de IM. Se analizaron sensibilidad, especificidad, valor predictivo positivo (VPP), negativo (VPN), cociente probabilidad positivo y negativo con programa estadístico PRIMER 4,06®. Resultados: 45 pacientes con SCA SDST. El 65,9 por ciento de género masculino. Rango de edades entre 38 y 82 con promedio de 63,4±16,4 años. Se registraron como factores de riesgo: tabaquismo 68,1 por ciento, hipertensión arterial 46,7 por ciento, dislipidemia 29,3 por ciento, cardiopatía coronaria 13,8 por ciento. Características electrocardiográficas: pared anterior 43,5 por ciento, inferior 36,7 por ciento, bloqueo completo de rama izquierda 19,8 por ciento. Se obtuvo una sensibilidad de 85,7 por ciento, especificidad: 60 por ciento, valor predictivo positivo: 80,2 por ciento y valor predictivo negativo: 54,7 por ciento. Cociente de probabilidad positiva 2,41 y cociente de probabilidad negativa 0,24 Taylor. Chi cuadrado por Mantel Haenszel p=0,0007. Conclusiones: La h-FABP es un marcador precoz, de fácil implementación y rápido resultado en el infarto agudo del miocardio, potencialmente útil para el diagnóstico en IM dada su alta sensibilidad y cociente de probabilidad.

Evaluación bioquímica del estado nutricional en un grupo de puérperas. Estudio preliminar / Biochemical evaluation of nutritional status in a group of puerperal women. Preliminary study

Se determinaron los niveles de proteína transportadora de vitamina A, transtirretina (prealbúmina), transferrina, inmunoglobulina A, fracción C3 de complemento en suero y de inmunoglobulina A total en saliva, en un grupo de 109 mujeres durante los primeros días post-parto. Las muestras de sangre y saliva no estimulada de las pacientes en ayunas se mantuvieron a -20 ºC hasta ser analizadas por inmunodifusión radial en placas de agarosa. Los resultados (media ± DE), expresados como porcentaje de las proteínas totales, fueron: 0,06 ± 0,02; 0,24 ± 0,06; 6,36 ± 1,19; 2,70 ± 0,47 y 3,76 ± 1,17 para proteína transportadora de vitamina A, transtirretina, transferrina, C3 e IgA sérica respectivamente, mientras que los de IgA en saliva fueron de 14,3 ± 10,3 mg/dL. Los valores de proteína transportadora de vitamina A y transtirretina fueron significativamente menores a los de referencia, lo que sugeriría un posible estado nutricional materno deteriorado que no se reflejó en el peso de los recién nacidos

Evaluación nutricional del paciente HIV+/SIDA: parámetros bioquímicos / Nutritional status of patients with VIH+/AIDS: biochemical parameters

La evaluación nutricional del paciente HIV+/SIDA debe incluir: 1) anamenesis alimentaria, 2) estudio físico y clínico, 3) estudio de la composición corporal y 4) análisis bioquímicos. La literatura internacional considera que la evaluación bioquímica en SIDA, debe incluir como mínimo los niveles de albúmina, transferrina, proteínas séricas totales, colesterol, hemoglobina y hematocrito y que la depleción de alguno de ellos es indicativa de deficiencia proteica o anemia, respectivamente. Por otra parte, otros indicadores de rutina tales como el número total de linfocitos y pruebas cutáneas no serían de utilidad debido al impacto de la enfermedad sobre los marcadores inmunológicos. La mayor parte de los antecedentes que aporta la bibliografía internacional especializada, en relación con el estado nutricional de éstos pacientes, han sido obtenidos en adultos con enfermedad avanzada y ante la presencia de una variedad de infecciones oportunistas. No obstante, es limitada la información disponible en relación con el estado nutricional evaluado a través de indicadores precoces, en las primeras etapas de la enfermedad y en especial en la población infantil. La elección de adecuados parámetros bioquímicos funcionales permitiría además el seguimiento y evaluación de la terapia de alimentación implementada

Valores de referencia para proteína transportadora de hormona de crecimiento en una población pediátrica normal / Normative values of growth hormone binding protein, GHBP, for a chilean pediatric population

Circulating concentrations of the high affinity growth hormone binding protein (GHBP) may be a marker of GH receptor density as well as GH sensiffvity. Goal: To determine values of GHBP for a normal Chilean pediatric population. Methods : We determined GHBP levels in 73 males and 73 females between 4 to 15.5 years and 4 to 16.8 years respectively, divided in 7 groups according to age and puberal status. Results: The population was normally distributed in weight, height and body mass index (BMI). GHBP activity increased up to Tanner IV in males and Tanner III in females, and decreased slightly thereafter in Tanner V and IV respectively. There was a significant difference between GHBP levels of preschool children and those found in Tanner II to V in both sexes (p<0.05). In adition, we found a positive correlation between GHBP vs weight, height and BMI (p<0.001) in males and females. Conclusion : The availability of this methodology allows us to establish the normative value of GHBP in our population and provides useful information to interpret GH circulating levels in children with growth disorders

Leptina y sistema reproductivo / Leptin and the reproductive system

La leptina es una hormona proteica recientemente descubierta, la cual es producida por los adipocitos. Esta actúa regulando el apetito, el peso corporal y la termogénesis. Su posible rol como modulador en el eje reproductivo se ha inferido de una cepa de ratas carentes de leptina, que se caracterizan por ser obesas, diabéticas e infértiles y en las que el administrar esta hormona se producen cambios como disminución del apetito, aumento del gasto energético y recuperación de la fertilidad. Estos fenómenos han motivado una gran cantidad de estudios para establecer el rol la leptina en el sistema reproductivo. Se revisa la literatura existente sobre leptina y su acción sobre los cambios de peso corporal, pubertad, sistema nervioso central y periférico, ovarios y embarazo

Immunoreactive riboflavin carrier protein concentration during ovulatory cycle in the common marmoset (Callithrix jachhus): role of estrogen.

Common marmoset, a non-human primate, is increasingly being used as a model system in reproductive endocrinology. Marmosets do not menstruate but have normal cycle length of 28 +/- 2 days. The presence of protein immunologically and functionally similar to the well characterized chicken riboflavin carrier protein (cRCP) has been demonstrated in circulation in pregnant marmosets. Marmoset RCP (mRCP) has been partially purified and the molecular weight of the immunoreactive protein is similar to cRCP. The source of RCP in rodents appears to be maternal liver, suggesting thereby that RCP levels could be modulated by changing hormonal pattern that occurs during the cycle. To study the hormonal control of marmoset RCP, immunoreactive RCP levels were monitored during normal cycle. Plasma progesterone was estimated by RIA and mRCP was measured using a heterologous cRCP RIA. When mRCP and progesterone were analysed for a period of 40 days (n = 5) in adult females, very low amount of mRCP was measured during the luteal phase and a single sharp peak was observed during the follicular phase of the cycle. These data suggested that the induction of mRCP was regulated by estrogen. Direct evidence for the role of estrogen in the elaboration of RCP, was the observation that exogenous administration of estradiol 17 B to immature marmosets resulted in a time and dose dependent increase in plasma RCP levels. As early as 24 hr following hormonal administration, a measurable increase in mRCP with a maximum increase, 5-fold over the zero period was seen 3 days following a single administration of estradiol 17 B (5 mg/kg body wt). RCP levels declined thereafter and was indistinguishable by day 7. These studies indicate that the marmoset RCP levels are regulated by estrogen.

Lipophorin as a lipid carrier in the hemolymph of the horseshoe crab, Limulus polyphemus

A high-density lipoprotein (HDL) was obtained from the hemolymph of Limulus polyphemus in yields generally less than 30 micrograms/ml by ultracentrifugal flotation. SDS-PAGE revealed two apolipoproteins with masses similar to those of apolipophorins (apoLp-I, 265 +/- 14 kDa; apoLp-II, 89 +/- 6 kDa). Lipid composition was different from both insect lipophorin and crustacean HDL, and showed less diacylglycerols than triacylglycerols (3.8 and 36.2 of total lipids, respectively). Since Limulus polyphemus is closely related to precambrian chelicerates, our results confirm that lipophorin was present early in the evolution of arthropods.

Serum level of iron and transferrin in pregnancy and postpartum period.

This study presents a composite picture of haemoglobin (Hb), serum level of iron (SI), total iron binding capacity (TIBC) and percent iron saturation of transferrin in women during different trimesters of pregnancy and postpartum period. The results were correlated with age and parity. A total of 75 subjects, 15 from each trimester and 15 postpartal, were studied and compared with 15 nonpregnant normal subjects. Signs of increased iron demand, increased iron turnover and obvious iron deficiency, were demonstrated throughout pregnancy, by decrease in haemoglobin, SI, percent iron saturation of transferrin and increased TIBC; especially in older age group and multigravidae. SI, TIBC and percent iron saturation of transferrin are more sensitive indices of iron status and provide us an opportunity to replenish iron stores of an iron deficient pregnant mother at an earlier date thus preventing anaemia.

Biochemistry of the evolution of Triatoma infestans: XI. Hemolymph lipophorin

Se aisló y purificó la lipoforina del T.infestans a partir de hemolinfa de machos adultos por ultracentrifugación en gradiente de densidad en dos etapas. Esta lipoproteína tiene una densidad de 1.10 g/ml y está constituida por 53% de proteínas y 47% de lípidos. El radio de Stokes (Rs) de la molécula, determinado por cromatografía de filtración en gel, es aproximadamente de 73A y e;l peso molecular (Mr) calculado por el método de Margolis, es de 743 000 daltons. La lipoforina contiene dos apoproteínas: apolipoforina I (apoLp-I) con Mr = 255 000 y apolipoforina II (apoLp-II) con Mr = 78 000, siendo ambas glicosiladas. La composición de aminoácidos de la apoLp-I y de la apoLp-II presenta un elevado contenido de aspartato, glutamato y leucina y muy pequeña cantidad de metionina y cisteína. Los lípidos de la lipoforina comprenden: diacilgliceroles (41.4% de los lípidos totales), fosfolípidos (31.5%), hidrocarburos (12.2%), ácidos grasos libres (6.1%), colesterol (4.7%) y triacilgliceroles (4.1%). La fosfatidiletanolamina es el fosfolípido predominante con cantidades menores de fosfatidilcolina. Al tratar la lipoforina con tripsina, la apoLp-I sufre ruptura proteolítica, mientras que la apoLp-II es resistente. La anisotropía de fluorescencia del difenilhexatrieno (DPH) incluido en la lipoforina señala una fuerte interacción lípido-apoproteína, la cual no se modifica después de una extensa proteólisis de la apoLp-I con tripsina. Durante la tripsinización de la lipoproteína no se detectó...

Studies on the effect of folic acid supplement on folate and vitamin B12 status in children.

The effect of folic acid supplement (15 mg folic acid per day) for 5 weeks was studied on a group of 5 children aged 8-12 years who were admitted to hospital. The result was compared to a control group of 5 children who were given a placebo. After supplementation, both serum and red cell folate levels in the experimental group significantly increased, i.e., 15 fold (82.0 ng/ml) and 4 fold (880 ng/ml), respectively. Serum UFBP decreased considerably while TFBP showed no significant alteration which resulted in the elevation of the % saturation to its maximum value. These findings indicated that the supplementary folic acid not only increased both serum and red cell folate levels and saturated nearly all serum UFBP but also elevated the % saturation markedly. There were no definite changes of serum vitamin B12, UBBC, TBBC and TC levels of the experimental group from those of the control group. There were slightly but not significantly increased blood haemoglobin and haematocrit levels in both groups of children. This indicated that folic acid supplement had no definite effect on vitamin B12 and haematological findings in this study.

Serum folate and folic acid binding proteins in iron deficiency anaemia.

Serum and red cell folate and folic acid binding protein (FABP) concentrations were determined on 20 iron deficiency anaemic children of both sexes aged 6--12 years. All cases had haemoglobin level less than 12 gm% or haematocrit less than 36% with low serum iron and elevated unsaturated iron binding capacity. Serum folate levels in the anaemic group was not significantly different from that of normal subjects while red cell folate level was significantly lower in the anaemic group. However, all cases had red cell folate levels higher than 100 ng/ml. There was a direct relationship between the haemoglobin concentration and serum folate level. Serum FABP level in the anaemic group was found to be significantly higher than that of normal subjects and showed no correlation with haemoglobin, haematocrit, serum or red cell folate levels. The significance of elevated serum FABP was discussed.

Serum vitamin B12, serum and red cell folates, vitamin B12 and folic acid binding proteins in women taking oral contraceptives.

Serum and red cell folate, FABP, serum vitamin B12 and vitamin B12 binding proteins were determined in 20 women taking oral contraceptives continuously for at least one year. Studies were also performed on 50 apparently healthy women with history of never taken or not taking oral contraceptives for at least one year as a control group. Serum vitamin B12 level, UBBC and TBBC in women taking oral contraceptives were slightly but not significantly lower than those of the control group. TCI and TCIII increased with a decreased TCII, so that UBBC was within the normal limit. Serum folate was non-significantly lower while red cell folate was significantly lower in the oral contraceptive group than those of the control group. However, all cases of the former showed red cell folate over 200 ng/ml. A highly significant increased serum FABP was demonstrated in the women taking oral contraceptives. This was probably due to the increased synthesis of the FABP in order to bind more folate from the low serum folate and the hormonally induced stimulation.

Serum vitamin B12 and folate levels, vitamin B12 and folic acid binding proteins in patients with primary carcinoma of the liver.

Serum vitamin B12, folic acid, vitamin B12 and folic acid binding protein concentration were determined in 31 patients with primary carcinoma of the liver. Serum vitamin B12 level was found to be higher in 16 of 31 (52%) patients with carcinoma of the liver and the mean value was also significantly higher than that of the control group. There was no significant difference between the mean values of serum UBBC of these 2 groups. TCI and TCIII increased while TCII decreased considerably in the patient group. Serum folate level in patients with primary carcinoma of the liver was significantly lower than that of the control group. About 39% of these patients had serum folate level lower than the lowest value of the control group. Serum FABP in the former group was also significantly higher than that of the latter group.