Hypoglycosylation is a common finding in antithrombin deficiency in the absence of a SERPINC1 gene defect.

UNLABELLED: Essentials We investigated the molecular base of antithrombin deficiency in cases without SERPINC1 defects. 27% of cases presented hypoglycosylation, transient in 62% and not restricted to antithrombin. Variations in genes involved in N-glycosylation underline this phenotype. These results support a new form of thrombophilia. Click here to listen to Dr Huntington's perspective on thrombin inhibition by the serpins SUMMARY: Background Since the discovery of antithrombin deficiency, 50 years ago, few new thrombophilic defects have been identified, all with weaker risk of thrombosis than antithrombin deficiency. Objective To identify new thrombophilic mechanisms. Patients/methods We studied 30 patients with antithrombin deficiency but no defects in the gene encoding this key anticoagulant (SERPINC1). Results A high proportion of these patients (8/30: 27%) had increased hypoglycosylated forms of antithrombin. All N-glycoproteins tested in these patients (α1-antitrypsin, FXI and transferrin) had electrophoretic, HPLC and Q-TOF patterns indistinguishable from those of the congenital disorders of glycosylation (rare recessive multisystem disorders). However, all except one had no mental disability. Moreover, intermittent antithrombin deficiency and hypoglycosylation was recorded in five out of these eight patients, all associated with moderate alcohol intake. Genetic analysis, including whole exome sequencing, revealed mutations in different genes involved in the N-glycosylation pathway. Conclusions Our study provides substantial and novel mechanistic insights into two disease processes, with potential implications for diagnosis and clinical care. An aberrant N-glycosylation causing a recessive or transient antithrombin deficiency is a new form of thrombophilia. Our data suggest that congenital disorders of glycosylation are probably underestimated, especially in cases with thrombosis as the main or only clinical manifestation.

¿Son aplicables los criterios analíticos generales para definir el hipotiroidismo en personas con síndrome de Down? / Are suitable general clinic criteria for defining hypothyroidism in people with Down syndrome?

Las diversas series publicadas sobre la prevalencia de las alteraciones tiroideas en las personas con síndrome de Down (SD) muestran una gran dispersión de resultados, aunque todas coinciden en señalar una frecuencia mayor que en la población general. La causa de estas diferencias puede que dependa del método de selección de la muestra. En este trabajo se estudia una población sana de adolescentes con SD, perteneciente a la Asociación de Málaga, seleccionada aleatoriamente, al margen del circuito asistencial. Al valorar la tirotropina (TSH) como parámetro bioquímico para definir la función tiroidea, resulta que la media de la distribución de la población con SD estudiada se sitúa 2 desviaciones estándar por encima de la población general. Estos datos muestran que son dos poblaciones diferentes, por lo que sería necesario definir los criterios de normalidad e hipotiroidismo subclínico, dudoso o patológico, y proponer nuevas pautas para iniciar el tratamiento (AU)

Studies on the prevalence of thyroid disorders in people with Down syndrome (DS) show a wide dispersion of results. However, most of these studies agree in indicating a greater frequency than in the general population. The cause of these differences may depend on the method of sample selection. In this work we studied a healthy population of adolescents with DS of the Association of Málaga, selected randomly and regardless of the medical care. Mean TSH distribution, used here as a tool to define the biochemical thyroid function of the studied DS population, was two standard deviation higher than the mean for the general population. These data show that in terms of TSH the DS population is a distinct population with respect to the general population. This clearly indicates that it would be necessary to identify and define new criteria to establish what is normal, subclinical hypothyroidism, borderline or pathological, and to propose new treatment guide (AU)

Functional analysis of two haplotypes of the human endothelial protein C receptor gene.

OBJECTIVE: To confirm the effect of the endothelial protein receptor gene (PROCR) haplotypes H1 and H3 on venous thromboembolism (VTE), to study their effect on endothelial protein C receptor (EPCR) expression in human umbilical vein endothelial cells, and to investigate the functionality of H1 tagging single-nucleotide polymorphisms in an in vitro model. APPROACH AND RESULTS: Protein C (PC), activated PC, and soluble EPCR (sEPCR) levels were measured in 702 patients with VTE and 518 healthy individuals. All subjects were genotyped for PROCR H1 and H3. Human umbilical vein endothelial cells isolated from 111 umbilical cords were used to study the relation between PROCR haplotypes, PROCR mRNA, cellular distribution of EPCR, and rate of PC activation. Finally, the functionality of the intragenic PROCR H1 single-nucleotide polymorphisms was analyzed using a luciferase-based method. We confirmed that individuals carrying H1 have reduced VTE risk, increased plasma activated PC levels, and reduced plasma sEPCR levels and that individuals with the H3H3 genotype have an increased VTE risk and increased plasma sEPCR levels. In cultured human umbilical vein endothelial cells, H1 is associated with increased membrane-bound EPCR, increased rate of PC activation, and reduced sEPCR in conditioned medium, but does not significantly influence PROCR mRNA levels. In contrast, H3 is associated with reduced membrane-bound EPCR and increased sEPCR in human umbilical vein endothelial cell-conditioned medium, higher levels of a truncated mRNA isoform, and a lower rate of PC activation. Finally, we identified the g.2132T>C single-nucleotide polymorphism in intron 1 as an intragenic H1-specific functional single-nucleotide polymorphism. CONCLUSIONS: These results support a protective role of PROCR H1 against VTE and an increased risk of VTE associated with the H3 haplotype.

Comparison of a new chemiluminescent immunoassay for von Willebrand factor activity with the ristocetin cofactor-induced platelet agglutination method.

Measuring von Willebrand factor (VWF) activity is essential for the diagnosis of von Willebrand disease (VWD). The VWF activity is usually assessed based on measurement of the ristocetin cofactor (VWF:RCo). However, that test is technically challenging and has high intra- and inter-assay variabilities. A new automated chemiluminescent immunoassay VWF activity has recently become commercially available (HemosIL AcuStar von Willebrand Factor Ristocetin Cofactor Activity). The main objective of this study was to evaluate this new method and to compare it with the VWF:RCo assay as the reference method. We studied 91 samples, 18 healthy volunteers samples and 73 samples from patients (VWF:RCo level <50 IU dL(-1) ): 29 type 1 VWD, 13 type 2A, 5 type 2B, 5 type 2M, 3 type 2N, 5 type 3, 4 type 3 under treatment, 5 type 3 carriers and 4 samples with other pathologies. The HemosIL AcuStar VWF:RCo assay was 96% sensitive and 100% specific for detecting VWF abnormalities. The good analytical performance, and the sensitivity and specificity of HemosIL AcuStar VWF:RCo to detect VWF deficiency renders it a suitable method for VWD screening.

Assessment of the thrombin generation assay in haemophilia: comparative study between fresh and frozen platelet-rich plasma.

The severity of haemophilia A has traditionally been classified by the dosage of factor VIII (FVIII) by one-step coagulation tests. However, an homogeneous group of patients with similar FVIII levels show clinical heterogeneity and 10-15% of the patients classified as severe haemophilia do not have a severe bleeding phenotype. Traditional tests used for measuring FVIII are not capable of detecting other prohaemorrhagic or prothrombotic factors. Global tests as the thrombin generation assay (TGA) may detect these haemostatic factors. So TGA may be an additional tool for classifying the actual severity of haemophilia. Our group is carrying out correlation tests between FVIII and TGA in platelet-poor and -rich plasmas (PPP and PRP, respectively). PRP has the inconvenience that must be done freshly soon after blood extraction. Our aim is to study the differences between TGA performed with fresh and frozen PRP and PPP and its implementation in multicenter studies. We included 70 patients with severe haemophilia A in prophylactic treatment. Venous blood drawing was obtained prior to administration of FVIII, at the trough levels. FVIII measurement and TGA were performed in fresh and frozen PRP and PPP. The platelet absence caused a significant decrease in TGA although PPP and PRP correlated well. Frozen samples gave different results in PPP, but there were no significant differences between fresh and frozen PRP. This fact enables using frozen PRP in multicenter studies with a TGA-specialized laboratory for reclassifying haemophilia severity and for pharmacokinetic studies with TGA.

Role of microRNAs in gynecological pathology.

microRNAs (miRNAs) are 21-22 nucleotide non-coding RNAs that regulate gene expression and play fundamental roles in biological processes. These small molecules bind to target mRNAs, leading to translational repression and/or mRNA degradation. Aberrant miRNA expression is associated with several human diseases such as cancer, cardiovascular disorders, inflammatory diseases and gynecological pathology. The present article reviews the role of miRNAs in four gynecological disorders that affect the ovary or the uterus, one benign and frequent disease (endometriosis) that is classified as a tumor-like lesion and three malignant gynecological diseases (endometrial, cervical and ovarian cancers). Endometriosis, defined as the presence of endometrium outside the uterus, is one of the most frequent benign gynecological diseases. Similarly to tumor metastasis, endometriotic implants require neovascularization to proliferate, invade the extracellular matrix and establish an endometriotic lesion. Despite its high prevalence and incapacitating symptoms, the exact pathogenic mechanism of endometriosis remains unsolved. A relationship between endometriosis and gynecological cancer, especially ovarian cancer, has been reported. Endometriosis is a multifactorial and polygenic disease, and emerging data provide evidence that a dysregulation of miRNA expression may be involved. miRNAs appear to be potent regulators of gene expression in endometriosis, raising the prospect of using miRNAs as biomarkers and therapeutic tools in this disease. In cancer, miRNAs have an important role as regulatory molecules, acting as oncogenes (oncomiRs) or tumor suppressors. Endometrial cancer is one of the most frequent gynecological malignancies in the developed countries. Cervical cancer, also one of the most common cancers in women, is associated with high-risk human papillomaviruses although this infection alone may not be enough to induce the malignant transformation. Ovarian cancer is the fifth leading cause of all cancer-related deaths among women. Over 80% of cases are diagnosed at an advanced stage, with a reduced five-year survival rate. Recent studies have shown that miRNAs are aberrantly expressed in different human cancer types, including endometrial, cervical and ovarian cancer, and that specific dysregulated miRNAs may act as biomarkers of patients' outcome. Recently, miRNAs have been detected in serum and plasma, and circulating miRNA expression profiles have now been associated with a range of different tumor types. Their accessibility in peripheral blood and stability given the fact that miRNAs circulate confined within exosomes, make researchers foster hope in their role as emerging biomarkers of cancer and other disorders. The development of therapies that might block the expression or mimic the functions of miRNAs could represent new therapeutic strategies for any of the aforementioned gynecological disorders.

Evaluación de tecnologías sanitarias nuevas y emergentes. Propuesta de clasificación / Evaluation of new and emerging health technologies. Proposal for classification

Objetivo. Revisar y desarrollar una propuesta de clasificación de tecnologías sanitarias (TS) evaluadas por las Agencias de Evaluación de Tecnologías Sanitarias (AETS). Métodos. Revisión por expertos de AETS de una propuesta de clasificación de TS. Análisis de sus aportaciones y sugerencias de modificación. Reelaboración de la propuesta de clasificación. Pilotaje con médicos. El emplazamiento fue el Sistema Sanitario Público Andaluz (SSPA) y las AETS españolas. Los participantes eran expertos de AETS y médicos tutores de MIR (médicos internos residentes). La metodología consistió en la actualización de la clasificación de TS previamente realizada por el equipo de investigación, la revisión por expertos de las AETS españolas, el análisis cualitativo y cuantitativo de respuestas y la reelaboración de la clasificación y pilotaje con médicos asistenciales sobre 12 informes de evaluación de las AETS. Resultados. Se obtuvieron 11 categorías temáticas que se clasifican en 6 grandes grupos matrices en función de su finalidad: 1, tecnologías preventivas; 2, tecnologías diagnósticas; 3, tecnologías terapéuticas; 4, tecnologías diagnósticas y terapéuticas; 5, tecnologías organizativas, y 6, gestión del conocimiento y calidad. En el pilotaje se observó la coincidencia en la clasificación de 8 de los 12 informes revisados por los médicos. Conclusiones. En el presente estudio se han consensuado 11 categorías temáticas de TS y se ha propuesto una nueva clasificación de TS con doble entrada, según tipo de TS considerada y según finalidad de la misma. En opinión de los expertos participantes, la clasificación de la labor de las AETS puede representar una herramienta útil para la gestión del conocimiento y la transferibilidad de la labor realizada. Además, una adecuada vehiculización de dicha labor facilitaría su acceso a los usuarios, potenciando así su difusión(AU)

Aims. Review and develop a proposal for the classification of health technologies (HT) evaluated by the Health Technology Assessment Agencies (HTAA). Design. Peer review of AETS of the previous proposed classification of HT. Analysis of their input and suggestions for amendments. Construction of a new classification. Pilot study with physicians. Setting. Andalusian Public Health System. Spanish HTAA. Participants. Experts from HTAA. Tutors of family medicine residents. Method. HT Update classification previously made by the research team. Peer review by Spanish HTAA. Qualitative and quantitative analysis of responses. Construction of a new and pilot study based on 12 evaluation reports of the HTAA. Results. We obtained 11 thematic categories that are classified into 6 major head groups: 1, prevention technology; 2, diagnostic technology; 3, therapeutic technologies; 4, diagnostic and therapeutic technologies; 5, organizational technology, and 6, knowledge management and quality of care. In the pilot there was a good concordance in the classification of 8 of the 12 reports reviewed by physicians. Conclusions. Experts agree on 11 thematic categories of HT. A new classification of HT with double entry (Nature and purpose of HT) is proposed. Applicability. According to experts, the classification of the work of the HTAA may represent a useful tool to transfer and manage knowledge. Moreover, an adequate classification of the HTAA reports would help clinicians and other potential users to locate them and this can facilitate their dissemination(AU)

[Evaluation of new and emerging health technologies. Proposal for classification]. / Evaluación de tecnologías sanitarias nuevas y emergentes. Propuesta de clasificación.

AIMS: Review and develop a proposal for the classification of health technologies (HT) evaluated by the Health Technology Assessment Agencies (HTAA). DESIGN: Peer review of AETS of the previous proposed classification of HT. Analysis of their input and suggestions for amendments. Construction of a new classification. Pilot study with physicians. SETTING: Andalusian Public Health System. Spanish HTAA. PARTICIPANTS: Experts from HTAA. Tutors of family medicine residents. METHOD: HT Update classification previously made by the research team. Peer review by Spanish HTAA. Qualitative and quantitative analysis of responses. Construction of a new and pilot study based on 12 evaluation reports of the HTAA. RESULTS: We obtained 11 thematic categories that are classified into 6 major head groups: 1, prevention technology; 2, diagnostic technology; 3, therapeutic technologies; 4, diagnostic and therapeutic technologies; 5, organizational technology, and 6, knowledge management and quality of care. In the pilot there was a good concordance in the classification of 8 of the 12 reports reviewed by physicians. CONCLUSIONS: Experts agree on 11 thematic categories of HT. A new classification of HT with double entry (Nature and purpose of HT) is proposed. APPLICABILITY: According to experts, the classification of the work of the HTAA may represent a useful tool to transfer and manage knowledge. Moreover, an adequate classification of the HTAA reports would help clinicians and other potential users to locate them and this can facilitate their dissemination.

La controversia del Stop-test en la reeducación uroginecológica / No disponible

En este artículo se expone información general sobre la dinámica miccional y sobre el Stop-test; una técnica, tan defendida por unos comonegada por otros, para el aprendizaje de los ejercicios de Kegel, y que en la actualidad genera controversia entre distintos colectivos sanitarios.El diccionario define la controversia como una discusión larga y reiterada. Se produce en el mejor de los casos por una falta de información fidedigna, pero también obedece en ocasiones a intereses personales, economicistas, sociales, etc. ¿Cuántas controversias se han visto y sesiguen viendo en relación a las recomendaciones vacunales, sin hablar necesariamente de la gripe A? Gregory Benford, en 1980, comentó ensu llamada Ley de Controversia: «La pasión es inversamente proporcional a la cantidad de información real disponible». (AU)

In this article general information is exposed on the mictional dynamics and on the Stop-Test, a technique defended by many people butdenied by many others, for the training of the Kegel, exercises, at present generates controversy among different health professional groups.The dictionary defines the controversy as a long and repeated discussion. It is produced in the best of the cases for a lack of reliable information,but also obeys on occasions to personal interests, economicist, social, etc. How many controversies have been seen and keep being seen inrelation to the vaccination recommendations, without talking necessarily about the A Flu? Gregory Benford, in 1980, commented in his knownLaw of Controversy: «The passion is inversely proportional to the quantity of available real information»! (AU)

Influence of peritoneal fluid on the expression of angiogenic and proteolytic factors in cultures of endometrial cells from women with endometriosis.

BACKGROUND: Endometriosis, defined as the presence of endometrium outside the uterus, is one of the most frequent benign gynaecological diseases. It has been suggested that both endometrial and peritoneal factors, related to angiogenesis and proteolysis, can be implicated in this disease. The aim of this study was to evaluate the influence of peritoneal fluid on the expression of angiogenic and proteolytic factors in cultures of endometrial cells from women with and without endometriosis. METHODS: Endometrial cells were isolated, cultured and treated with endometriotic or normal peritoneal fluid. Vascular endothelial growth factor-A (VEGF-A), urokinase plasminogen activator (uPA), matrix metalloproteinase-3 (MMP-3) and their inhibitors including thrombospondin-1, plasminogen activator inhibitor-1 and MMP inhibitor type 1 (TIMP-1) mRNA levels were evaluated by quantitative RT-PCR, and protein levels were quantified by ELISA. RESULTS: Peritoneal fluid from women with endometriosis induced an increase in VEGF-A and uPA protein and VEGF-A mRNA and uPA mRNA levels in endometrial cell culture from women with (P < 0.01) and without endometriosis (P < 0.05). The highest levels of VEGF-A and uPA were observed in endometrial cell cultures from patients with endometriosis and treated with peritoneal fluid from women with endometriosis. CONCLUSIONS: Peritoneal fluid from women with endometriosis induced more VEGF and uPA expression in endometrial cell culture from women with endometriosis than did normal peritoneal fluid. Endometrial-peritoneal interactions increased angiogenic and proteolytic factors in endometrial cells, which could contribute to the development of endometriotic lesions.

Insights into the role of microRNAs in cardiac diseases: from biological signalling to therapeutic targets.

microRNAs have recently opened new pathways to explain gene expression and disease biology in many scenarios, including cardiac diseases. microRNAs are endogenous small non-coding RNAs that mediate post-transcriptional repression or messenger RNA degradation. By annealing to inexactly complementary sequences in the 3' untranslated region of the target messenger RNA, protein level is down-regulated. Several microRNAs appear to act cooperatively through multiple target sites in one gene and, conversely, most microRNAs can target several genes. miR-133 and miR-1 are specifically expressed in cardiac and skeletal muscle and control myogenesis, cardiac development, cardiac performance and cardiomyocyte hypertrophy (mainly by tuning transcription factors and other growth-related targets). They also modulate the expression of certain cardiac ion channels and related proteins with proarrhythmic effect. Besides them, other microRNAs have been shown to exert influence on the myocardial growth, the electrical balance and the angiogenesis processes that take place in the heart. Bioinformatics is a useful tool to identify potential targets of a given microRNA, although there is still substantial concern about their reliability. Experimental manipulation of microRNAs has provided a tantalizing basis to speculate that future research on microRNAs may yield important progress in the prevention of sudden cardiac death and in the treatment of cardiac heart failure. However, the final effect of the blockage of microRNAs in vivo remains unclear, since each of them can target hundreds of genes with different intensity. The era of the microRNAs in cardiovascular diseases has just started.

The -589C>T polymorphism in the interleukin-4 gene (IL-4) is associated with a reduced risk of myocardial infarction in young individuals.

BACKGROUND: Inflammatory reactions contribute to the development of arterial disease. We investigated the role of interleukin-4 (IL-4) in the development of myocardial infarction (MI) by genotyping patients with MI and control subjects for the -589C>T (rs2243250) single nucleotide polymorphism (SNP), which tags a functional haplotype of IL-4. METHODS AND RESULTS: Study of Myocardial Infarctions Leiden (SMILE) included 560 men with a first MI and 646 control subjects. The Valencia study included 305 patients with MI at T genotype was found [odds ratio (OR) 0.84; 95% CI 0.37-1.95 for -589TT and 0.82; 95% CI 0.62-1.07 for -589CT compared with -589CC]. In patients younger than 50 years, carriership of one or two -589T alleles was associated with a reduced risk of MI (OR 0.57: 95% CI 0.34-0.95). This result was replicated in the Valencia study, where carriers of one or two -589T alleles had a reduced risk of MI (OR 0.67: 95% CI 0.47-0.95), with a strong protective effect of the -598T allele in homozygous -589T (OR 0.33: 95% CI 0.10-1.05). In the control subjects of the Valencia study, the -589T allele was associated with reduced levels of F1+2. CONCLUSION: Our data indicate that the IL-4 haplotype tagged by the -589T allele reduces the risk of MI in young individuals.

Quantitative analysis of pork dry-cured sausages to quality control by NIR spectroscopy.

Near infrared spectroscopy technology (diode array instrument) was used to study the feasibility of applying quality controls to typical Spanish sausages by performing a proximate analysis (fat, moisture and protein) on the finished product (intact and homogenized). This could be used to provide quality controls at various stages once the finished product was obtained: finished product, storage, distribution and marketing. The selected models were calibrated and evaluated by cross and external validation. For intact products, coefficients of determination for calibration (R(2)) for fat, moisture and protein were 0.98, 0.93 and 0.97, respectively. These values for homogenised products were 0.99, 0.98 and 0.97, respectively. The standard errors of prediction (SEP) for external validation in intact products were 1.47%, 0.97% and 1.08% for fat, moisture and protein, respectively. In homogenised products, these values were lower: 0.71%, 0.41% and 0.95%, respectively.

Fibrinogen, plasma viscosity and blood viscosity in obesity. Relationship with insulin resistance.

Plasma viscosity (PV) and blood viscosity (BV) have been scarcely evaluated in morbid obese patients with no other concomitant cardiovascular risk factors. Contradictory results have been published regarding the influence of insulin resistance on these rheological parameters in obesity. In 67 severe or morbid obese patients without other cardiovascular risk factors (51 women and 11 men, aged 34+/-11 years), fibrinogen, PV and BV at native (nBV) and corrected 45% hematocrit (cBV) have been determined, and insulin resistance has been calculated with homeostasis model assessment (HOMA) index, in basal conditions and after a three month diet period. The same determinations were performed in 67 healthy volunteers (45 women, 22 men, aged 32+/-10 years) at baseline and three months later. When cases and controls were compared, obese patients showed higher fibrinogen levels (P<0.001), PV (P=0.050) and cBV (P=0.035), and showed a higher insulin resistance than the control group (P<0.001). Differences in PV were maintained after adjusting for BMI (P=0.001), but disappeared after adjusting for HOMA (P=0.391) fibrinogen (P=0.367) and LDL-chol (P=0.097). Differences between obese patients and the control group for cBV disappeared after adjusting for BMI (P=0.739), HOMA (P=0.744), fibrinogen (P=0.907), LDL-chol (P=0.283) and PV (P=0.112). The achieved weight loss (8.7+/-3.53%) was not accompanied by any changes in these rheological parameters (P>0.050). Obese patients show increased fibrinogen levels, PV and cBV. These rheological disturbances seem to be associated with insulin resistance and the metabolic syndrome, and do not seem to improve with moderate weight loss.

Oestrus expression and ovarian function in repeat breeder cows, monitored by ultrasonography and progesterone assay.

Ovarian ultrasonography and plasma progesterone levels were monitored in 37 lactating Holstein cows with a history of repeat breeding; the data obtained were analysed in conjunction with clinical and behavioural signs, to identify the aetiology of the syndrome. Differences were detected between RBCs displaying apparently normal cycles and others with irregular cycles. There were also differences in heat expression; a large number of repeat breeder cows (RBCs, 50%) displayed delayed or silent oestrus. Ovarian disorders were common in RBCs, and included ovarian cysts, mistimed AI, subluteal progesterone levels, luteal dysfunction or ovulation defects. Both ultrasonography and plasma progesterone assays are useful tools for ascertaining the aetiology of the repeat breeder syndrome.

Expression of angiogenic factors in endometriosis: relationship to fibrinolytic and metalloproteinase systems.

BACKGROUND: Endometriosis is a highly prevalent, benign disease in which the angiogenic, fibrinolytic and metalloproteinase (MMP) systems may be implicated. The objective of this study is to analyse mRNA expression and protein levels of several angiogenic factors and to correlate them with several components of the fibrinolytic and MMP systems in samples from 71 women with endometriosis and 50 controls. METHODS AND RESULTS: Eutopic endometrium showed higher mRNA expression of vascular endothelial growth factor (VEGF) in patients than in controls. However, ovarian endometrioma had lower VEGF mRNA levels than did the eutopic endometrium of patients. Similar results were obtained for VEGF protein levels. On the other hand, a significant increase in thrombospondin-1 (TSP-1) levels was observed in ovarian endometrioma than in eutopic endometrium. The peritoneal fluid from women with endometriosis showed a significant increase in VEGF, urokinase-type plasminogen activator (uPA) and MMP-3 levels than that of controls. A significant correlation was observed between the levels of VEGF and uPA in endometrium and in peritoneal fluid. CONCLUSIONS: Endometrium and peritoneal fluid from women with endometriosis have increased levels of VEGF, uPA and MMP-3 levels. Therefore, the development of endometriotic implants at ectopic sites may be facilitated, promoting the progress of the endometriosis.

Effect of carazolol on the oestrous behaviour and concentrations of luteinising hormone and steroids in lactating cows during the periovulatory period.

Twelve multiparous, cycling, lactating Holstein-Friesian cows were synchronised with prostaglandin F(2alpha) and treated with either 2.5 mg carazolol or saline. There were no differences between the peripheral blood concentrations of oestradiol or progesterone, but in the cows treated with carazolol the periovulatory surge of luteinising hormone was delayed, and oestrous behaviour was expressed later than in the control cows.

Expression of the fibrinolytic components in endometriosis.

Endometriosis is a benign gynaecologic disease defined as the presence of endometrial tissue outside the uterus. This tissue has the ability to implant at ectopic sites, such as ovary and peritoneum, where a local extracellular proteolysis might take place. An altered expression of several components of the fibrinolytic system in the endometrium and peritoneal fluid of women with the disease has been suggested as a key factor in the establishment of the endometriotic lesions. There is evidence of increased fibrinolytic activity in the eutopic endometrium of these women, resulting in endometrial fragments with a high potential to degrade the extracellular matrix and facilitate implantation. Proteolytic status is determined by the imbalance between plasminogen activators and plasminogen activator inhibitors, which are expressed differently depending on the type of lesion considered and the stage of the disease. The aim of the present study is to review the expression of the plasminogen activator system in endometriosis, and to consider the clinical implications and the possible further research efforts in this disease.

Circulating activated protein C is reduced in young survivors of myocardial infarction and inversely correlates with the severity of coronary lesions.

BACKGROUND: Cardiovascular risk factors for myocardial infarction (MI) are less frequent in younger than in older MI survivors. Therefore, the thrombotic component of MI may play a more important role at a young age. As activated protein C (APC) provides systemic anticoagulant and anti-inflammatory protection, a low plasma APC level may be an arterial thrombotic risk factor. AIM: To determine whether there is an association between reduced APC levels and early MI and severe coronary lesions. METHODS: APC was measured in 231 young MI survivors and 231 controls. RESULTS: Low APC levels were significantly associated with MI. Compared with the fourth quartile, the odds ratio (OR) for APC values in the first quartile was 3.7 [95% confidence interval (CI) = 2.1-6.4], and 3.2 (1.5-7.0) after adjustment for cardiovascular risk factors. Moreover, each decrease of 0.43 ng mL(-1) (1 SD) in APC increased the OR 1.7 times (1.4-2.2), and 1.5 times (1.2-1.9) after adjustment for cardiovascular risk factors. Low APC levels were also associated with the number of coronary arteries affected and with the severity of coronary lesions (P < 0.001). CONCLUSIONS: There is a significant association between low circulating APC levels and both early MI and the extent and severity of coronary atherosclerosis, which might be related to the anticoagulant and anti-inflammatory properties of APC.