Molecular characterization and clinical interpretation of BRCA1/BRCA2 variants in families from Murcia (south-eastern Spain) with hereditary breast and ovarian cancer: clinical-pathological features in BRCA carriers and non-carriers.

This is the first study performed in Murcia (south-eastern Spain) in which 592 families with hereditary breast and ovarian cancer were identified thanks to Genetic Counselling Units from this area over 6 years. Diagnostic performance was 18.1% and 194 different genetic variants were obtained. Variants with uncertain significance accounted for only 5.6% of the total number of reports, so our population has been well characterised. In BRCA1 gene, two novel variants were found (c.1859delT and c.3205C > T) and the most frequently detected mutations were c.68_69delAG, c.212 + 1G > A, c.5123C > A, c.211A > G and c.1918C > T, which together represented 56.67% of total pathogenic mutations. In BRCA2 gene, four recurrent variants were described (deletion of entire exon 2, c.9117G > A, c.3264dupT and c.3455T > G) representing 43.5% of the mutations in this gene. Mutation c.68_69delAG and deletion of entire exon 2 in BRCA1 and BRCA2 genes respectively were the most prevalent variants in our population. Regarding the genotype-phenotype relation, mutation c.212 + 1G > A appeared in an important percentage of breast and ovarian cancer cases, c.5123C > A in bilateral breast cancer and c.9117G > A in bilateral breast cancer and ovarian cancer. With respect to clinical-pathological characteristic, BRCA1/BRCA2 mutation carriers showed earlier onset age of breast tumour and higher risk of developing contra lateral breast cancer than non-informative cases. Moreover, association between either molecular subtype triple negative breast cancer or ovarian cancer and BRCA1 carriers was obtained.

Associations between oxidative stress biomarkers in different body fluids and reproductive parameters in male partners of subfertile couples / Asociaciones entre biomarcadores de estrés oxidativo en diferentes fluidos biológicos y parámetros reproductivos en varones de parejas subfértiles

Objective. To evaluate the relationships between oxidative stress (OS) biomarkers and total antioxidant capacity (TAC) in blood serum and seminal plasma, and their associations with semen quality and serum reproductive hormone concentrations in potential subfertile men. Material and method. A cross-sectional study was conducted on men (n = 122) attending an infertility clinic in the Murcia Region (Southern Spain) between 2012 and 2013. Concentrations of malondialdehyde (MDA), nitric oxide (NO) and TAC were measured in blood and semen. Follicle-stimulating hormone, luteinising hormone, testosterone, prolactin and oestradiol concentrations were measured in serum. Semen analyses were performed according to World Health Organization criteria. Correlation analysis and multiple linear regression models were performed, controlling for important covariates. Results. There was a significant inverse association between serum MDA concentrations and all sperm parameters, except for seminal volume. Serum TAC concentrations were positively related to sperm count and motility. A positive association was observed between seminal plasma NO levels and the percentage of morphologically normal sperm. With regard to reproductive hormones, serum MDA concentrations were positively related to FSH and LH levels, and TAC inversely associated with FSH levels. Conclusions. Our results suggest that oxidative stress may be associated with semen parameters and reproductive hormone levels in male partners of couples seeking infertility treatment. However, further studies are needed to confirm and extend these findings, in particular, with regard to serum reproductive hormones (AU)

Objetivo. Evaluar las correlaciones entre marcadores de estrés oxidativo (OS) y capacidad antioxidante total (TAC) en suero sanguíneo y plasma seminal, y sus asociaciones con calidad seminal y hormonas reproductivas en varones potencialmente subfértiles. Material y método. Estudio transversal realizado en varones (n = 122) que acudían a un servicio de infertilidad de Murcia entre 2012-2013. Las concentraciones de malondialdehído (MDA), óxido nítrico (NO) y TAC se midieron en sangre y semen. Se analizaron los niveles séricos de las hormonas foliculoestimulante, luteinizante, testosterona, prolactina y estradiol. Los análisis espermáticos se llevaron a cabo siguiendo las normas de la Organización Mundial de la Salud. Se utilizaron análisis de correlación y modelos de regresión lineal múltiple ajustando por covariables importantes. Resultados. Se mostró una asociación inversa significativa entre las concentraciones séricas de MDA y todos los parámetros espermáticos, excepto el volumen seminal. Las concentraciones séricas de TAC se relacionaron positivamente con el recuento y la movilidad espermática. Los niveles de NO en plasma seminal se asociaron directamente con el porcentaje de espermatozoides morfológicamente normales. Con respecto a las hormonas reproductivas, las concentraciones séricas de MDA se asociaron positivamente con los niveles de FSH y LH, y las de TAC se asociaron inversamente con los niveles de FSH. Conclusiones. Nuestros resultados sugieren que el estrés oxidativo estaría asociado con los parámetros seminales y hormonales en varones de parejas que consultan por problemas de infertilidad. Sin embargo, son necesarios más estudios para confirmar estos hallazgos, en particular con respecto al papel de las hormonas reproductivas (AU)

Situación actual del estado nutricional del yodo en gestantes de la región de Murcia, España / Current situation of nutritional state of iodide in pregnant women in Murcia region, Spain / SituaþÒo atual do estado nutricional do iodo em gestantes da regiÒo de Múrcia, Espanha

El objetivo de este trabajo consistió en identificar los niveles de yodo en el primer trimestre del embarazo en mujeres atendidas en centros de salud, pertenecientes al área sanitaria I de Murcia (España), así como la relación de dichos niveles con la ingesta y los suplementos de yodo. Por otra parte se realizó el estudio de la función tiroidea en el mismo grupo. Se realizó un estudio descriptivo funcional. El grupo de estudio consistió en 37 mujeres embarazadas, que habían acudido a la primera visita en su centro de salud correspondiente desde los meses de marzo hasta agosto de 2011. Las variables de estudio fueron: niveles de yodo en orina medidos en una muestra aislada de orina, frecuencia de la ingesta de yodo relacionada con la alimentación y suplementos (datos obtenidos mediante una entrevista personal y un cuestionario estructurado realizado entre las participantes del estudio), niveles de hormona tiroestimulante TSH y T4 libre ambas obtenidas a partir de una muestra de sangre. El 86% del grupo en estudio presentaba deficiencia de yodo. Hubo diferencias estadísticamente significativas en cuanto a la excreción urinaria de yodo, en la ingesta de sal iodada y de pescado. Sin embargo, cualquier otra variable no presentó diferencias significativas. Se hallaron tres embarazadas con hipotiroidismo subclínico y una presentó hipertiroidismo subclínico. Además, estos resultados mostraron que los niveles de TSH pueden ser más bajos en embarazadas que en la población general. En base a los datos de ioduria obtenidos, los suplementos de yodo en este grupo se consideraron insuficientes. Además, se concluye que sería recomendable incluir la determinación sistemática de T4 libre y TSH en el primer trimestre del embarazo, para corregir una posible disfunción tiroidea tan pronto como sea posible y así evitar daños al feto.(AU)

The aim of this work was to identify iodine levels in the first term of pregnancy in women attending health care centers of Sanitary Area I of Murcia (Spain), and the relationship of said levels with food intake and iodine supplements. Apart from that, thyroid gland function was assessed in the same group. A descriptive transversal study was performed. The sample group consisted of 37 pregnant women who had a first appointment at the corresponding midwifery service from March to August 2011. The variables studied were urinary iodine levels through isolated sample collection, frequency of intake of iodine related to food and iodine supplements (data obtained through a face to face interview and a structured questionnaire administered among the participats in the study), and levels of thyroid-stimulating hormone TSH and free T4 obtained from a blood sample. Eighty-six per cent of the study group had iodine deficiency. Statistically significant differences were found in urinary iodine excretion, in intake of iodine salt and of sea food. However, no other variable studied presented any statistically significant difference. Three pregnant women were found with subclinical hypothyroidism and one presented subclinical hyperthyroidism. Furthermore, these results showed that TSH levels can be lower in pregnant women than in the general population. On the basis of the normal urinary iodine excretion obtained, the supply of iodine in the study group is insufficient. Moreover, It would be desirable to include the systematic determination of free T4 and TSH in the first term of pregnancy so as to to correct a likely thyroid dysfunction as soon as possible in order to avoid possible damage to the foetus.(AU)

O objetivo deste trabalho consistiu em identificar os níveis de iodo no primeiro trimestre de gravidez em mulheres atendidas em centros de saúde, pertencentes O área sanitária I de Múrcia (Espanha), bem como na relaþÒo de tais níveis com a ingestÒo e os suplementos de iodo. Por outra parte foi realizado o estudo da funþÒo tireoidiana no mesmo grupo. Foi feito um estudo descritivo funcional. O grupo de estudo consistiu em 37 mulheres grávidas, que tinham assistido O primeira visita no centro de saúde correspondente, desde marþo até agosto de 2011. As variáveis de estudo foram: níveis de iodo em urina, medidos numa amostra isolada de urina, frequÛncia da ingestÒo de iodo relacionada com a alimentaþÒo e suplementos (dados obtidos através de uma entrevista pessoal e um questionário estruturado realizado entre as participantes do estudo), níveis de horm¶nio tiroestimulante TSH e T4 livre, ambas obtidas a partir de uma amostra de sangue. 86% do grupo em estudo apresentava deficiÛncia de iodo. Houve diferenþas estatisticamente significativas quanto O excreþÒo urinária de iodo, na ingestÒo de sal iodado e de peixe. Entretanto, qualquer outra variável nÒo apresentou diferenþas significativas. Foram encontradas trÛs mulheres grávidas com hipotireoidismo subclínico e uma apresentou hipertireoidismo subclínico. Além disso, estes resultados mostraram que os níveis de TSH podem ser mais baixos em mulheres grávidas que na populaþÒo geral. Com base nos dados de iodúria obtidos, os suplementos de iodo neste grupo foram considerados insuficientes. Além do mais, seria recomendável incluir a determinaþÒo sistemática de T4 livre e TSH no primeiro trimestre da gravidez, para corrigir uma possível disfunþÒo tireoidiana assim que for possível e, desse modo, evitar danos no feto.(AU)

Second trimester angiotensing-converting enzyme and uterine artery Doppler as predictors of preeclampsia in a high-risk population.

OBJECTIVE: To investigate whether serum angiotensing-converting enzyme (ACE) and uterine artery Doppler (UAD) are useful markers as predictors of preeclampsia (PE) in a high-risk population. METHODS: Patients at risk of PE (n = 68) were subclassified as having PE (n = 8) or no PE (n = 60). Blood samples were obtained between 19 and 22 weeks of gestation. Doppler ultrasound of the uterine arteries was done at the time of blood sampling. Maternal serum ACE was determined through spectrophotometry assay (A15 Biosystem, ATOM, Barcelona, Spain). RESULTS: Comparing the group who presented PE with the one who was not developed it, we found significant differences for ACE (54.2 ± 21.2, 38.1 ± 12.3 U/L; p = 0.003); the pulsatility index (PI) (1.2 ± 0, 3.1 ± 0.3; p = 0.032) and resistance index (RI) (0.7 ± 0.1, 0.5 ± 0.1; p = 0.004). The AUC for ACE was 0.724, so we selected the cutoff of 36.5 U/L (sensitivity: 62.5% and specificity: 86.7%). The AUC for PI was 0.652 choosing a cutoff of 1.4 (sensitivity: 57.1% and specificity: 93.1%). The AUC for RI was 0.712 and the cutoff of 0.7 (sensitivity of 71.4% and specificity: 89.6%). The combination that allowed us to increase the diagnostic performance was the ACE+RI with Doppler study, increasing the AUC to 0.872. CONCLUSIONS: ACE, PI and RI as parameters of Doppler study were useful predictors of PE in the second trimester of gestation. The best combination to increase the diagnostic performance was ACE with the RI.

Placental growth factor, soluble fms-like tyrosine kinase 1 and progesterone as diagnostic biomarkers for ectopic pregnancy and missed abortion.

OBJECTIVE: The aim of this study is to investigate if progesterone, placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt1) serum levels are useful markers to differentiate between ectopic pregnancy (EP), missed abortion (MA) and viable intrauterine implantation pregnancy (IUP). METHODS: We designed a retrospective case-control study which included 100 pregnant women (50 EP and 50 MA) at 6-8 weeks of gestation with ßhCG serum levels between 800 and 3500 UI/L and a viable IUP group. Progesterone, PlGF and sFlt-1 levels were measured with an electrochemiluminescence assay (Roche Diagnostics, Manheim, Alemania). A non parametric test was used to compare the markers in the different groups and we used receiver operating characteristic (ROC) curve analysis to calculate the area under the curve (AUC). RESULTS: When we compared the EP group with the MA group, we didn't find significant differences for PlGF (15.1[13.2-17.4]/16.7[12.8-18.7] pg/mL) (p=0.275). We only obtained significant differences for progesterone (9.1[3.1-16.8]/2.6[1.3-6.1] ng/mL) (p<0.001) and sFlt-1 (84[65-96]/126[94-256] pg/mL) (p<0.001). The AUC for progesterone was 0.756 and the cutoff point with better sensitivity and lower false positive rate was 6 ng/mL (sensitivity=60%, specificity=72.7%). The AUC for sFlt-1 was 0.842 and the cutoff point was 93 pg/mL (sensitivity=84.5%, specificity=86.3%). The combination of both markers allowed us to increase the AUC to 0.910. CONCLUSIONS: In conclusion, the present study suggests that sFlt-1 could be a useful marker to differentiate between an EP or a MA when ßhCG levels are similar in both groups. The combination of sFlt-1 with progesterone helps to increase the diagnostic performance.

Performance evaluation of biochemical and ultrasound markers for the screening of chromosomal numerical abnormalities in the first trimester of pregnancy.

BACKGROUND: To estimate the effectiveness of the first-trimester combined screening test in our population, departing from the results of diagnostic sensitivity and false positive rate (FPR), and checking some important parameters in prenatal screening. METHODS: The test was evaluated on 14250 pregnant women. The following variables were studied: the number of invasive techniques and the reasons for using such techniques, newborns with chromosomal abnormalities, total number of births, variation of biochemical markers throughout the gestational weeks, and MoM (multiple of the median) for biochemical and ultrasound markers. RESULTS: An important coverage and a decreased number of invasive techniques were obtained. For our population of pregnant women, the best gestational week to determine free beta-hCG and PAPP-A would be week 11 in which the best discrimination was found between affected and non affected fetuses for the three trisomies researched. We propose the cut-off 1/350, because it is the best one to increase sensitivity without exceeding the 5% FPR. CONCLUSIONS: Combined screening should be offered to pregnant woman, preferentially at week 11. Although different cut-offs for this prenatal test have been recommended by scientific societies, biochemical laboratories should set their own cut-off for getting the best sensitivity and FPR results. There should be a good level of collaboration between the laboratory and each participating ultrasound unit in order to ensure an optimal use of the first-trimester combined screening test.

Intoxicación por sobredosificación de vitamina D en un lactante / Poisoning by overdose of vitamin d in an infant

El objetivo de esta nota técnica es la descripción y comentarios de un caso clínico reciente de intoxicación por sobredosificación por vitamina D, y la correcta interpretación clínica y de los parámetros de laboratorio. Caso clínico. Lactante de 6 meses en tratamiento con Biominol® (suplemento vitamínico), ingresó debido a un estado de decaimiento e irritabilidad. Las analíticas iniciales muestran concentraciones de calcio iónico en sangre de 2,11mmol/L (intervalo de referencia (IR): 1,15-1,29mmol/L), y concentración de calcio total plasmático de 5,5mmol/L (IR: 2,25-2,75mmol/L). En nuestro laboratorio, las vitaminas D2 y D3 fueron determinadas por cromatografía líquida de alta resolución (HPLC), y por un método electroquimioluminiscente, que mide la vitamina D total. Los valores de vitamina D2 fueron 419ng/mL y vitamina D total 482ng/mL (IR: 30-100ng/mL). La intoxicación de vitamina D tuvo origen exógeno, debido al incremento de vitamina D2. El diagnóstico definitivo fue hipercalcemia severa secundaria a intoxicación por vitamina D y nefrocalcinosis secundaria a esta con función renal normal con hipercalciuria. Como conclusión, cabe destacar la importancia de la correcta dosificación de los pacientes y la determinación de las diferentes formas de vitamina D para averiguar su origen, realizando una correcta interpretación (AU)

The objective of this technical note describes and comments on a recent clinical case of poisoning by overdose of vitamin D, and the correct interpretation of clinical and laboratory parameters. Vitamin D is a fat-soluble vitamin involved in the absorption of calcium and phosphorus in the intestine. Administration of high doses for prolonged periods can cause hypercalcemia, leading to kidney failure and renal calcifications. Clinical case. The definitive diagnosis of this patient was severe hypercalcemia secondary to exogenous vitamin D poisoning, and nephrocalcinosis secondary to this with normal renal function with hypercalciuria. In conclusion, the correct dosing of patients and determination of different forms of vitamin D to trace its origin and making a correct interpretation is important. Male, 6 months old in treatment with Biominol® (vitamin D supplement), was admitted to the emergency department because of a state of decline and irritability. The initial analytical results showed an ionized calcium concentration in blood of 2.11mmol/L (reference interval (RI): 1.15 - 1.29mmol/L), and plasma total calcium concentration of 5.5mmol/L (RI: 2.25-2.75mmol/L). In our laboratory, Vitamin D2 and D3 were determined by liquid chromatography high resolution (HPLC), and an electrochemiluminescence method. The results showed a vitamin D2 419ng/mL and total vitamin D 482ng/mL (RI: 30-100ng/mL). It was found that the vitamin D overdose was of exogenous origin, due to increased vitamin D2 (AU)

Intoxicación por ingesta de levotiroxina (Eutirox(R)) / Intoxication due to ingestión of levothyroxine (Eutirox(R))

La levotiroxina es el fármaco de elección en el tratamiento del hipotiroidismo. La intoxicación con levotiroxina no es muy frecuente pero puede acompañarse de complicaciones secundarias sobre todo cardiovasculares. La unión de hormonas tiroideas a proteínas plasmáticas es muy elevada (99,97%), debido a esto, la levotiroxina no se elimina por hemodiálisis ni hemoperfusión. Tiene una vida media de 7 días. Se presenta el caso de una niña de 6 años que acude a la puerta de urgencias por sospecha de ingesta de levotiroxina en cantidades desconocidas. Se valora que parámetros del seguimiento de la función tiroidea es significativo de la mejora del paciente (AU)

Levothyroxine is the drug of choice of Hypothyroidism's treatment. The poisoning (intoxication) with levothyroxine is rare, but, overcoat it can be accompanied of secondary cardiovascular complications. Binding of thyroid hormones to plasma proteins is very high (99.97%), due to this, the levothyroxine is not removed by hemodialysis or hemoperfusion. It has an average life of 7 days. We hereby present the case o a 6-year-old girl who comes at the Emergency Service for suspicion of ingestion of levothyroxine in unknown quantities. There are valued what parameters of the follow-up of the tyroid function it is significant of the improvement of the patient (AU)

Analysis of cholinesterases in human prostate and sperm: implications in cancer and fertility.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are postulated to play non-cholinergic roles in cellular physiology. The probable implication of cholinesterases (ChEs) in several human pathologies prompted us to study the cholinergic components in the male reproductive system. Surgical pieces of prostatic cancer (PC) and benign prostatic hyperplasia (BPH) were analyzed for AChE and BChE activity. Loosely (S1) and tightly (S2) bound AChE and BChE forms were characterized by sedimentation analysis. The mean AChE activity in BHP samples was 2.38+/-0.56 mU/mg (nmol of the substrate hydrolysed per minute and per milligram protein) and 2.57+/-0.61 mU/mg in S1 and S2, respectively. The AChE activity did not vary with cancer, showing 2.46+/-0.45 mU/mg in S1 and 2.70+/-0.53 mU/mg in S2 from PC samples. Amphiphilic dimers and monomers and hydrophilic dimers of AChE were identified in BHP and PC tissues. Their contribution was affected by cancer with a great increase in hydrophilic dimers in the cancerous samples. Significant levels of both AChE and BChE activities were found in seminal fluid and homogenates from spermatozoids. Enzymatic activity dropped in samples with abnormal seminal parameters as sperm count and mobility.

Cancer-associated differences in acetylcholinesterase activity in bronchial aspirates from patients with lung cancer.

In non-neuronal contexts, ACh (acetylcholine) is thought to be involved in the regulation of vital cell functions, such as proliferation, differentiation, apoptosis and cell-cell interaction. In airways, most cells express the non-neuronal cholinergic system, each containing a specific set of components required for synthesis, signal transduction and ACh hydrolysis. The aim of the present study was determine the expression of cholinergic system components in bronchial aspirates from control subjects and patients with lung cancer. We conducted an analysis of cholinergic components in the stored soluble and cellular fraction of bronchial aspirates from non-cancerous patients and patients diagnosed with lung cancer. The results show that the fluid secreted by human lung cells contains enough AChE (acetylcholinesterase) activity to control ACh levels. Thus these findings demonstrate that: (i) AChE activity is significantly lower in aspirates from squamous cell carcinomas; (ii) the molecular distribution of AChE in both bronchial cells and fluids consisted of amphiphilic monomers and dimers; and (iii) choline acetyltransferase, nicotinic receptors and cholinesterases are expressed in cultured human lung cells, as demonstrated by RT-PCR (reverse transcriptase-PCR). It appears that the non-neuronal cholinergic system is involved in lung physiology and lung cancer. The physiological consequences of the presence of non-neuronal ACh will depend on the particular cholinergic signalling network in each cell type. Clarifying the pathophysiological actions of ACh remains an essential task and warrants further investigation.

Cholinesterase activity of human lung tumours varies according to their histological classification.

The probable involvement of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in cancer and the relevance of cholinergic responses for lung cancer growth prompted us to study whether cholinesterase activity of human lung is altered by malignancy. Surgical pieces of non-small lung carcinomas (NSLC) and their adjacent non-cancerous tissues (ANCT) were analysed for AChE and BChE activities. AChE activity in adenocarcinoma (AC) was 7.80 +/- 5.59 nmol of substrate hydrolysed per min and per mg of protein (mU/mg), the same as in their ANCT (8.83 +/- 4.72 mU/mg; P = 0.823); in large cell carcinoma (LCC), 7.52 +/- 3.32 mU/mg, approximately 50% less than in their ANCT (15.39 +/- 5.66 mU/mg; P = 0.043); and in squamous cell carcinoma (SCC), 1.39 +/- 0.58 mU/mg, 80% less than in ANCT (6.08 +/- 2.88 mU/mg; P = 0.003). BChE activity was 5.85 +/- 3.20 mU/mg in AC and 9.56 +/- 3.38 mU/mg in ANCT (P = 0.022); 2.94 +/- 2.01 mU/mg in LCC and 6.50 +/- 6.63 mU/mg in ANCT (P = 0.068); and 4.49 +/- 2.30 mU/mg in SCC and ANCT 6.56 +/- 4.09 mU/mg (P = 0.026). Abundant AChE dimers and fewer monomers were identified in lung and, although their distribution was unaffected by cancer, the binding with concanavalin A revealed changes in AChE glycosylation between SCC and their ANCT. The fall in BChE activity affected all molecules, with a strong decrease of the amphiphilic tetramers. Western blotting revealed protein bands with the expected mass of the principal AChE subunits, and the deeper intensity of the protein signal in SCC than in healthy lung, in lanes loaded with the same units of AChE activity, supported an augment in the amount of AChE protein/unit of AChE activity in SCC. The increased availability of acetylcholine in neoplastic lung, resulting from the fall of cholinesterase activity, may enhance cholinergic signalling and contribute to tumour progression.

[Biochemical bone markers and bone mass study in recently postmenopausal women without osteoporosis]. / Marcadores bioquímicos de remodelado en el estudio de la masa ósea en la mujer con menopausia reciente sin osteoporosis.

BACKGROUND AND OBJECTIVE: To date, there have not been performed enough studies in Spain to analyze the usefulness of biochemical bone markers in postmenopausal and non-osteoporotic women. POPULATION AND METHOD: We studied several groups of women, ages between 17 and 30 years, 30-45 years, premenopausal and recently postmenopausal in order to know the reference values of some biochemical bone markers along 2 years in premenopausal and postmenopausal women (postmenopausal divided in 2 groups: those under treatment with ordinary hormonal replacement therapy [HRT], and those without it). RESULTS: Values of biochemical bone markers were higher in postmenopausal and in 17-30 years group than in premenopausal and 30-45 years group (p < 0.05). Absolute values and the change in bone markers (%) were higher in postmenopausal and non-osteoporotic women under HRT than in those without HRT (% change: OC, 35,72 vs 4.45 [p < 0.01]; ALPo, 13,13 vs 27.06 [p < 0.01]; NTx, 42.74 vs 10.93 [p < 0.01]; fDPD, 21.07 vs 28.49 [p < 0.05]; betaCrossLaps, 50,17 vs 23.04 [p < 0.01]). CONCLUSIONS: We have defined reference values in our region and have proved that biochemical bone markers (absolute values and their change from the basal value) represent a useful tool in monitoring hormonal replacement therapy in recently postmenopausal and non-osteoporotic women.

Marcadores bioquímicos de remodelado en el estudio de la masa ósea en la mujer con menopausia reciente sin osteoporosis / Biochemical bone markers and bone mass study in recently postmenopausal women without osteoporosis

FUNDAMENTO Y OBJETIVO: En España no hay estudios acerca de la utilidad a medio plazo de los marcadores bioquímicos de remodelado óseo en mujeres con menopausia reciente y sin osteoporosis. POBLACIÓN Y MÉTODO: Constituimos 5 grupos de mujeres de edades comprendidas entre 17-30 años, 35-45 años, premenopáusicas y posmenopáusicas recientes sin osteoporosis, y calculamos los valores de referencia para cada grupo. Posteriormente dividimos el último grupo en dos(sin/con adhesión a tratamiento hormonal sustitutivo [THS] ordinario) para seguir la evolución de los marcadores y la densidad mineral ósea a lo largo de 2 años. RESULTADOS: Constatamos que tanto en el grupo de mujeres de 17-30 años como en mujeres con menopausia los valores de los marcadores eran superiores a los encontrados en mujeres premenopáusicas y el grupo de 35-45 años (p < 0,05). Los valores absolutos de los marcadores y sobre todo el porcentaje de cambio semestral frente al valor basal difieren entre mujeres con menopausia sin THS y con THS (porcentaje de cambio con/sin THS: osteocalcina [OC] -35,72 frente a 4,45 [p < 0,01]; isoenzima ósea de la fosfatasa alcalina [ALPo]-13,13 frente a 27,06 [p < 0,01], telopéptido aminoterminal del colágeno tipo I, -42,74 frente a -10,93 [p < 0,01]; de oxipiridolina libre, -21,07 frente a 28,49 [p < 0,05]; β Cross-Laps, -50,17 frente a 23,04 [p < 0,01]), y se corresponden con un mantenimiento de la masa ósea a los 2 años en el grupo con THS frente a su disminución en el grupo sin THS (p < 0,05).CONCLUSIONES: Los marcadores bioquímicos de remodelado óseo no sólo presentan distintos valores de referencia en grupos de distinta edad, sino que son útiles en la evaluación de la pérdida de masa ósea ante la aplicación de un THS ordinario también en mujeres con menopausia reciente sin osteoporosis

BACKGROUND AND OBJECTIVE: To date, there have not been performed enough studies in Spain toanalyze the usefulness of biochemical bone markers in postmenopausal and non-osteoporotic women. POPULATION AND METHOD: We studied several groups of women, aget between 17 and 30 years, 30-45 years, premenopausal and recently postmenopausal in order to know the reference values of some biochemical bone markers along 2 years in premenopausal and postmenopausal women (postmenopausal dividez in 2 groups: those under treatment with ordinary hormonal replacement therapy [HRT], and those without it). RESULTS: Values of biochemical bone markers were higher in postmenopausal and in 17-30 years group than in premenopausal and 30-45 years group (p < 0.05). Absolute values and the change in bone markers (%) were higher in postmenopausal and non-osteoporotic women under HRT than in those without HRT (% change: OC, -35,72 vs 4.45 [p < 0.01]; ALPo, -13,13 vs27.06 [p < 0.01]; NTx, -42.74 vs -10.93 [p < 0.01]; fDPD, -21.07 vs 28.49 [p < 0.05]; β Cross Laps, -50,17 vs 23.04 [p < 0.01]). CONCLUSIONS: We have defined reference values in our region and have proved that biochemical bone markers (absolute values and their change from the basal value) represent a useful tool in monitoring hormonal replacement therapy in recently postmenopausal and non-osteoporotic women (AU)

Acetylcholinesterase biogenesis is impaired in lung cancer tissues.

Studies cited by Cowan et al. [J. Appl. Toxicol. 23, 177 (2003)] indicate existence of inflammatory and cholinergic pathways in both nerve agents and sulfur mustard (HD) injury. Increase in AChE synthesis and neurite extension was noted after exposure to HD [K.W. Lanks et al., Exp. Cell Res. 355 (1975)]. Moreover, anti-inflammatory drugs reduce the dermal, respiratory and ocular damage caused by exposure to HD. On the other hand, recent studies have noted the involvement of neuro-inflammatory processes during exposure to the nerve agents sarin or soman [Cowan et al., 2003]. The use of various anti-inflammatory drugs in addition to the classical antidotal drugs (e.g. atropine and oximes) caused decrease in certain toxic symptoms and inflammation-induced brain damage. Our new bifunctional drugs (Scheme 1) are based on CNS-permeable molecular combination of pseudo-reversible AChE inhibitor (pyridostigmine, PYR) coupled via a hydrophobic spacer (octyl or decyl hydrocarbon chain) to a non-steroidal anti-inflammatory drug (NSAID) such as Ibuprofen or Diclofenac (Scheme 1). This study evaluates the efficacy of certain bifunctional compounds against HD and soman poisoning in mice in vivo.

[Addition of an angiotensin II receptor blocker to maximal dose of ACE inhibitors in heart failure]. / Adición de un ARAII al tratamiento con dosis máximas de IECA en la insuficiencia cardíaca.

In heart failure, the benefits of adding angiotensin-receptor blockade to ACE inhibitors have been studied only with submaximal doses of ACE inhibitors. We included 20 patients (LVEF 24 7%, NYHA II-III), with no clinical or therapeutic variations in the previous three months, who were receiving maximal doses of ACE inhibitors. We added losartan 50 mg once a day. At six months, SBP decreased (115 8 vs. 106 9 mmHg; p = 0.001), LVEF increased (24.4 7 vs. 34.1 7%; p < 0.001), ventricular end-diastolic volumes decreased (220 58 vs 190 46 ml; p = 0.007), and SPAP decreased (43 8 vs. 35 7 mmHg; p < 0.001). Seven patients improved one degree on the NYHA scale (p = 0.004), but VO2max did not change (20.8 5.2 vs. 21.8 5.0 ml/kg/min, p = 0.120). Plasma levels of norepinephrine, at rest and maximal exercise, brain natriuretic peptide, and renin were similar. After maximum ACE inhibitor doses, the addition of losartan is safe and associated with an improvement in ventricular function and NYHA functional class, but with no change in neurohormonal status.

Adición de un ARAII al tratamiento con dosis máximas de IECA en la insuficiencia cardíaca / Addition of an Angiotensin II receptor blocker to maximal dose of ACE inhibitors in heart failure

En la insuficiencia cardíaca, el beneficio de la combinación ARAII e inhibidores de la enzima conversiva de la angiotensina (IECA) ha sido estudiado sólo con dosis submáximas del IECA. Incluimos a 20 pacientes (FEVI 24 ñ 7 por ciento, NYHA II-III), sin cambios clínicos ni terapéuticos en los 3 meses previos, que recibían dosis máximas del IECA, y asociamos 50 mg/día de losartán. A los 6 meses, la presión arterial sistólica descendió (115 ñ 8 frente a 106 ñ 9 mmHg; p = 0,001), la FEVI aumentó (24,4 ñ 7 frente a 34,1 ñ 7 por ciento; p < 0,001), los volúmenes diastólicos (220 ñ 58 frente a 190 ñ 46 ml; p = 0,007) y sistólicos (164 ñ 49 frente a 125 ñ 38 ml; p = 0,001) disminuyeron y la PSAP descendió (43 ñ 8 frente a 35 ñ 7 mmHg; p < 0,001). Siete pacientes mejoraron un grado NYHA (p = 0,008), sin mejoría significativa del VO2máx (20,8 ñ 5,2 frente a 21,8 ñ 5,0 ml/kg/min; p = 0,120).Las concentraciones de noradrenalina en reposo y en el momento de máximo esfuerzo, así como del péptido natriurético cerebral y de la renina, fueron similares. Con dosis máximas del IECA, la adición del ARAII fue segura, asociándose a una mejora de la función ventricular y la clase funcional, pero sin cambios en el estado neurohormonal (AU)