Placental Proinflammatory State and Maternal Endothelial Dysfunction in Preeclampsia.

OBJECTIVE: To evaluate the placental and decidual gene expression and maternal and umbilical serum concentrations of tumor necrosis factor alpha, interleukin 6 (IL-6), IL-8, IL-10, IL-1 receptor antagonist (IL-1RA), intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1), along with the proinflammatory/anti-inflammatory cytokine ratios in women with preeclampsia (PE) vs. women with normal pregnancy (NP), and to analyze PE classified as early- (EO) and late-onset (LO). METHODS: This cross-sectional study was performed with 50 women with PE (EO n = 30, LO n = 20) and 50 women with NP. Tissue gene expression levels were measured by real-time RT-PCR. Cytokines and adhesion molecules serum concentrations were measured by immunoassays. RESULTS: In PE, placental expression of IL-10 and IL-1RA was lower, while placental IL-8/IL-1RA ratio and maternal concentrations of VCAM-1 were higher vs. NP. In EO, placental expression of IL-10 was lower, while placental IL-8/IL-10 and IL-8/IL-1RA ratios were higher than LO and NP. Maternal concentrations of IL-6 were higher in LO than EO and NP. Throughout PE, maternal VCAM-1 concentrations were higher vs. NP. No significant differences were observed in the decidual expression and umbilical concentrations of the markers between the groups. CONCLUSION: PE associates with a proinflammatory placental state; however, EO associates with a proinflammatory placental state, while LO associates with systemic maternal inflammation. Both subtypes associated with maternal endothelial dysfunction.

Similar to Adiponectin, Serum Levels of Osteocalcin are Associated with Mammographic Breast Density in Postmenopausal Women.

OBJECTIVE: Breast cancer is the most common type of cancer in Canadian women and worldwide. Mammographic density is a well-established breast cancer risk. Recent evidence suggested inverse correlations among adiponectin, osteocalcin, and the risk developing breast cancer. The objective of the study was to evaluate the relationship between breast density and adiponectin and osteocalcin concentrations. METHODS: A cross-sectional study was performed in 239 women, age range 40 to 60. Mammographic density, serum adiponectin, and osteocalcin levels were measured. According to the Wolfe method, participants were divided into those with low-risk and high-risk pattern mammograms. RESULTS: The study population included 107 premenopausal and 132 postmenopausal women. Parameters were no different between women with low-risk and high-risk patterns. In obese postmenopausal women, the high-risk pattern mammogram group had significantly higher values of adiponectin and osteocalcin compared with the low-risk pattern group. Multiple linear regression analyses showed that adiponectin and osteocalcin levels were associated with high-risk pattern mammograms. CONCLUSION: Adiponectin and osteocalcin levels were directly associated with high-risk pattern mammograms in obese postmenopausal women. These results do not support the use of adipokines as biomarkers; nevertheless, the most important factor is to assess the risk through breast density.

[Clinical implications of basic research in preeclampsia: immunological tolerance]. / Implicaciones clínicas de la investigación básica de la preeclampsia: tolerancia inmunológica.

Preeclampsia is one of the main causes of maternal and perinatal mortality in the world; however, the pathophysiologic pathways haven't been clearly elucidated. It is thought to result from a breakdown of maternal tolerance to paternal antigens in placenta that start an immune response against the trophoblast inducing a defective placentation and a hipoxic/isquemic environment which in turn triggers a systemic inflamatory response. This review gives an overview of the mechanims involved in maternal tolerance, how these are disrupted in preeclampsia, and how they contribute to the inflamatory response.

[Commentary on the Nobel Prize that has been granted in Medicine-Physiology, Chemistry and Physics to noteable investigators]. / Comentario sobre los Premios Nobel de Medicina-Fisiología, Química y Física otorgados a investigadoras notables.

The Nobel Prize was established by Alfred Nobel in 1901 to award people who have made outstanding achievements in physics, chemistry and medicine. So far, from 852 laureates, 45 have been female. Marie Curie was the first woman to receive the Nobel Prize in 1903 for physics and eight years later also for chemistry It is remarkable that her daughter Irene and her husband also received the Nobel Prize for chemistry in 1935. Other two married couples, Cori and Moser, have also been awarded the Nobel Prize. The present commentary attempts to show the female participation in the progress of scientific activities.

[Efficacy and adverse effects of oral antidiabetic agents]. / Eficacia y efectos adversos de los antidiabéticos orales.

The management of type 2 diabetes is still a challenge and a conundrum for treatment intensity and choice of pharmaceutical agent. There is also uncertainty about possible cardiovascular adverse effects.

[Pap test used for detection of cellular changes associated with human papillomavirus]. / El Papanicolaou para detectar cambios celulares por el virus del papiloma humano.

Human papilloma virus can infect any mucous of the body and can cause cancer of the uterine cervix. This suggests recommending the Papanicolaou smear combined with a test for detection of human papillomavirus with a frequency interval of 3 years, since it grants greater information and fidelity to the result. The detection studies should begin at the age of 21 years and should stop at 65 years age. Until recently specific treatments did not exist to treat human papilloma virus, but recently some drugs that have demonstrated good effectiveness in curing the infection of human papilloma virus. One example is glycirrhicinic acid, which has demonstrated fewer adverse effects, as well as the possibility that its systemic employment allows treatment of lesions that are difficult to approach. The medical recommendations should be in constant revision, since a clinical trial can modify the interpretation of what is necessary to individualize each patient's treatment.

El virus del papiloma humano puede infectar cualquier mucosa del cuerpo y causar cáncer del cuello uterino. La última recomendación sugiere realizar la prueba de Papanicolaou combinada con una prueba para detección del virus del papiloma humano aproximadamente cada tres años. Los estudios de detección deben iniciarse a los 21 años de edad y debe detenerse el seguimiento a los 65 años si no existen factores de riesgo asociados que indiquen lo contrario. Hasta hace poco no existían tratamientos específicos contra el papiloma, pero han surgido algunos fármacos que han demostrado buena efectividad como el ácido glicirricínico, con menos efectos adversos y posibilidad de su empleo sistémico para combatir las lesiones difíciles. Cuando no son tratadas, las lesiones por el virus del papiloma humano pueden tener implicaciones sobre la reproducción, la recurrencia de infecciones genitales oportunistas y la anatomía. La identificación y modificación de los cofactores son de suma importancia ya que con ello se modula la persistencia y la progresión de la infección del virus del papiloma humano a neoplasia. Las recomendaciones médicas deben estar en constante revisión, ya que el juicio del clínico puede modificar la interpretación, por lo que es necesario personalizar el tratamiento a cada paciente.

Women with gestational diabetes develop glucose intolerance with high frequency within one year postpartum.

OBJECTIVE: To investigate the incidence of glucose intolerance postpartum in women with gestational diabetes (GDM) and assess body weight, cholesterol and triglyceride concentrations after delivery. METHODS: This was a study of an initial cohort of 100 women with GDM who were tested at 6 weeks, 6 months, and 1 year postpartum. Postpartum evaluations were glucose tolerance, weight and cholesterol and triglycerides. RESULTS: Impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) was present in 36.5% of 52 participants who were assessed at 6 weeks postpartum and diabetes in 17.3%; the remaining 48 women failed to return for the 3 evaluations. By 6 months, IFG/IGT was demonstrated in 55.8% and diabetes in 32.7% of the women. At 1 year, 46.2% exhibited IFG/IGT and 48% diabetes. Moreover, the weight was higher in those women who presented IFG/IGT (75.5 ± 15.2 kg, mean ± SD) and diabetes (79.0 ± 16.2 kg) compared with those who had normal glucose tolerance (65.3 ± 14.5 kg; p < 0.05). In addition, triglycerides were higher in mothers with glucose intolerance (181.3 ± 85.9 mg/dl in IFG/IGT and 230.9 ± 90.9 mg/dl in diabetes) than in women with normal glycemia (147.8 ± 11.2 mg/dl; p < 0.05). CONCLUSION: We demonstrated an increased incidence of women exhibiting glucose intolerance within 1 year postpartum, mainly in those who remained obese.

[Infection therapeutic modalities in human papillomavirus]. / Terapéutica en infección por virus del papiloma humano.

Human papillomavirus (HPV) genital it can infect any mucous of the body and to cause cancer of the uterine cervix. Until recently specific treatments did not exist on this infection, for what had to destroy or to remove the injured tissue by diverse procedures, what could have obstetric repercussions in young women. Recently some surgical modalities and topical drugs have arisen, as well as of systemic employment that allow to arrive to the lesions difficult to approach, and have demonstrated good effectiveness to cure the infection for HPV, for what an analysis of the medical treatment of this infection type is made.

[The treatment of hypercholesterolemia is in a crossroad]. / El tratamiento del colesterol alterado en una encrucijada terapéutica.

In order to correct the high level of cholesterol in blood is necessary to improve the life style which includes proper nutrition and physical exercise, but frequently is added some medication. The initial medication that is used is a stantin which decreases total cholesterol and low density cholesterol associated with increment in high density cholesterol in order to prevent cardiovascular involvement. It is frequent the addition of other medicaments, such as niacin or ezetemiba to achieve a greater effect on cholesterol disorders. The effectively of anti-cholesterol elevation should be evaluated by the occurrence of cardiovascular events, instead of the improvement in biochemist markers.

[Diagnosis of premature menopause measuring circulating anti-Müllerian hormone]. / Diagnóstico de menopausia prematura usando la medición de la hormona anti-mülleriana circulante.

The production of anti-müllerian hormone for the ovarian follicles begins near the puberty and the circulating levels begin to descend progressively in the stage of the pre-menopause coinciding with the depletion follicular and in consequence the menstrual cycles become irregular, frequently anovulatories. Therefore, concentration of anti-müllerian hormone shows a close correlation with follicular reserve and reproductive capacity, more than FSH and estradiol measurements. We described two patients that developed premature ovarian failure without previous diagnosis and therefore just were treated pharmacologically with estrogen-progestagen to induce menstrual bleeding. In blood of both patients was found low levels (< or = 4 ng/mL) of anti-müllerian hormone, and by means of sonography the absence of follicles was demonstrated in the ovaries. Has intended that premature ovarian failure could be of a chromosomal dysfunction, similar to other gonadal dysgenesias, another explanation of the mechanism is that it could be for development of some autoimmunity dysfunction. Therefore, the combined hormonal substitution of estrogen with progestagen should stay during several years to avoid the complications for the lack of estrogens; in some cases, could be informed on offering the pregnancy possibility by means of the attended fertilization using ovules donor.

[Diagnostic and therapeutic misunderstandings derived from case-control studies and meta-analyses]. / Confusión diagnóstica y terapéutica derivada de los estudios clínicos controlados y los metanálisis.

Up to now, clinical trials and meta-analyses have been considered as essential for medicine, based on evidence and clinical practice, but recently there has been controversial information in the scientific literature regarding the diagnosis and treatment of several maladies. It was generally accepted that early detection of cancer could lead to appropriate and successful treatment, in particular in cancer located in breast, prostate gland, colon, and lungs. Nevertheless, there are reports which show the difficulty to detect the malignancy and development of cancer. As to the use of medicaments, the controversy arises from the possibility of undesirable side effects, which limit their beneficial effect. Likewise, long-term treatment of chronic diseases makes the prediction of adverse effects difficult. It is concluded that the physician should analyze all sorts of information, including that originated from observational and personal experience, in order to reach a correct diagnosis as well as the appropriate therapy. There are no truisms originating totally from clinical trials and meta-analyses.

[Gregorio Marañón, a pioneer of endocrinology, 50 years after his death]. / Gregorio Marañón, un pionero de la endocrinología, cumple 50 años de su fallecimiento.

Gregorio Maranon born and dead in Madrid (1887-1960), was a Spanish physician, scientist, historian, philosopher, humanist, and writer, considered one of the most brilliant Spanish intellectuals of the 20th century. He was also a Republican and fought the Primo de Rivera dictatorship, though later expressed his disagreement with communism. Maranon participated closely with the process of exile of Alfonso XIII. From a very early age he learned several foreign languages and was an avid reader, hence he became in contact with the intellectual circles of the time and cultivated a close friendship with Perez Galdos, Menendez-Pelayo, Ortega y Gasset, Pio Baroja, Unamuno, Lerroux among several outstanding and eminent figures of the famous Generation of 14. In Medical School he had great teachers such as Santiago Ramon y Cajal, and later he specialized in endocrinology and became professor of the specialty in the Complutense University in Madrid, moreover he founded the Institute of Medical Pathology and the Department of Experimental Endocrinology, henceforth he contributed to establish the relationship between endocrinology and psychology. At the beginning of the instauration of the Republic, Maranon became a member of the constituent assembly and the parliament, but soon became disillusioned of communism and left Spain before the initiation of the Civil War, remaining in France until 1942 when he returned to Spain to reestablish his private practice, and soon the medical teaching at the hospital which now bears his name. Late work about history, poetry was elaborated at his Toledo Cigarral de Menores.

[Development of radioimmunoassay and its consequences in the medical research. A tribute to Rosalyn Yallow]. / El radioinmunoensayo y su impacto en la investigación. Tributo a Rosalyn Yallow.

Rosalyn Yalow lived all her life in the Bronx, New York, where she was born, educated, worked and met Solomon Berson, her scientific partner for a long time. Despite being a top student at Hunter College she was unable to be admitted to any graduate program in physics, mainly because she was Jewish and female. Later she joined the Veterans Administration Hospital in New York where she established the radioisotope laboratory. There she met Solomon Berson and formed the extraordinary scientific partnership and started publishing studies of radioactivity. Yalow received the Nobel Prize in Medicine and Phisiology or Medicine in 1977 and died on May 30, 2011.

[New trends in gestational diabetes]. / El nuevo enfoque hacia la diabetes gestacional.

It has been considered that gestational diabetes (GD) is onset along a pregnancy and resolves after delivery. It is also believed that GD is a risk factor for the development of diabetes; however it remains controversial the time of pregnancy for looking for and the diagnostic test and protocol to apply. Mother's age and obesity are closely associated with the presence of glucose intolerance; likewise there are an unsatisfactory number of women who return for evaluation after delivery. The purpose of the paper is to discuss this controversial topic and set out a point of view.

Pregnant woman from southern Peru with rabies infection who delivered a healthy baby.

Rabies in pregnancy is rare with a high mortality. We report a pregnant woman who developed urban rabies from the bite of an infected dog. An emergency Cesarean section was performed at 31 weeks of gestation, and a premature baby was delivered who survived and did not develop rabies. The mother, however, suffered a rapid clinical deterioration and was admitted to intensive care where a Milwaukee protocol was followed. The patient survived 19 months but developed severe neurological sequelae secondary to rabies encephalitis and finally died of respiratory failure.

[Estrogen therapy in menopause. Clinical study in evolution (KEEPS) to explain the risk-benefit dispute to administration]. / Terapia con estrógenos en la menopausia. Estudio clínico en evolución (KEEPS) para explicar la controversia del riesgo-beneficio de su administración.

The Kronos Early Estrogen Prevention Study (KEEPS) is a randomized clinical and controlled study, with the objective of clarifying the controversy that arisen previous studies about the risk-benefit factor with use of estrogens in postmenopausal women. Healthy women aged 42-58 years who are within 36 months of their last menstrual period have been recruited to receive either oral estrogens or patches of estradiol; in addition both groups are given oral micronized progesterone for 11 days of each month. Outcomes will be carotid intimae medial thickness and the accrual of coronary calcium; collaterally subrogate outcomes will be lipoproteins concentrations, coagulation markers, bone densitometry, mammography, skin characteristics and cognitive evaluation. The hypothesis consists in the presence of a window of therapeutic opportunity for the use of estrogens in low dose in healthy women with recent menopause.

[Genetic and hormonal effects on sexual differentiation. Paradoxically women require androgens and men estrogens]. / Efecto genético y hormonal sobre la diferenciación sexual. Paradójicamente la mujer requiere andrógenos y el hombre estrógenos.

It had been established that the sexual structure of a person was determined by the type of hormonal production, what gave biological specificity of the estrogens to women and androgens to men, but recently this functional specificity has lost base due to the biological activity described in different tissues of men and women, today known as endocrine paradox. There are hormonal events that show the need of estrogens to correct development in men and androgens to women. In men the absence of effect of the estrogens produces deficient ossification of skeleton, persistence of the growth cartilage and osteoporosis in adult men. In women the production of androgens by suprarenal glandules is required to obtain the complete feminization. In women with chirurgic-induced menopause, the relation between androgens and the stimulation of sexual response has been established. It has been described a hormone called kisspeptin, that it is attributed the potential to initiate the puberty because stimulates the hypothalamus; in absence of this hormone the women do not present their secondary sex characters, remaining immature sexually. The understanding of individuals needs of androgens and estrogens contribute to improve the control and care of the patient with hormonal deficiencies in any phase of the life.

[Care of insulin resistance in polycystic ovary syndrome]. / Atención de la resistencia a la insulina en el síndrome de ovarios poliquísticos.

Polycystic ovary syndrome (PCOS) constitutes the main cause of anovulatory sterility with a near occurrence to 7 %. The PCOS have not a constant hormonal profile, for it has been necessary the employment of approaches like those of Rotterdam to establish the presence of this dysfunction. A surprising discovery was the demonstration of the effect of the insulin on the ovary, that which modified the concept of the specificity in the action of the insulin on certain tissues, therefore a resistance stage to the action of insulin induces a compensatory hyperinsulinism to try to stimulate all the tissues, but in secondary form increases the dysfunction of the ovarian steroidogenesis. There are drugs known as "insulin sensitizers", used in the treatment of certain forms of diabetes mellitus, among those are metformin and tiazolidinediones (roziglitazone and pioglitazone), recently a compound has been used with formulation of amino acids and oligoelements (Diamel) that neutralizes the free radicals reestablishing the intracellular signs of the insulin at cellular level. It is important to guide that long term without correct the PCOS could have back effect since the insulin resistance is associates to a higher risk of increasing impaired glucose, diabetes, dyslipidemia, atherosclerosis and vascular disease. Therefore, preventive measures should be implemented that at present time are to the reach.

[Frequency of symptoms of the climacteric syndrome]. / Frecuencia de los síntomas del síndrome climatérico.

BACKGROUND: Menopause is the descent in circulating estrogens that manifests clinically for the climacteric symptoms. These symptoms motivate the patient to consult to the physician. OBJECTIVE: To know which are the symptoms that motivate women in the climacteric to begin hormonal therapy. MATERIAL AND METHOD: Atransverse study was settled, 692 patients from the menopause cohort of Endocrine Research Unit, Centro Médico Nacional, IMSS participated. All patients signed the letter of informed consent. Complete clinical evaluation and taking samples of veined blood for the hormonal determinations of LH, FSH and estradiol were carried out. The approach of evaluation of the clinical symptoms was made with the scale of Greene that values six components: psychological, anxiety, depression, somatic, vasomotor and sexual, which quantifies the presence and intensity of the climacteric symptoms. RESULTS: The four main symptoms that accompany the climacteric are: hot flushes, irritability, edginess and sickness. With the registered symptoms, the punctuation of the components in the scale of Greene showed a bigger frequency statistically with difference significant (p < 0.05) for the vasomotor and the depressive component compared with the rest of the components that integrate all the symptoms. CONCLUSIONS: Hot flushes and irritability are the symptoms found in the first time interview, also these are presented in more than half of the patients, therefore these symptoms can be considered as main cause to begin hormonal therapy. In accordance with the scale of Greene that allowed us to evaluate the symptoms in integrated form, the sexual component was a smaller frequency, maybe to that great number of patient does not dare to comment the sexual dysfunctions. However, at the moment has a wide therapeutic arsenal and forms of administration of estrogen therapy that have demonstrated to have a clinical-benefic effect for the control of the climacteric symptoms.

[Bone tissue as an endocrine gland]. / El tejido óseo se incorpora a la constelación hormonal.

Bone tissue was essentially considered as a mechanical structure; however is now well known that is the site of permanent bone remodelation. In addition, bone functions as an endocrine gland producing osteocalcin, which in turn interacts with other tissues, such as fat, pancreas and gastrointestinal tract. As a consequence, osteocalcin intervenes into glucose metabolism, peripheral insulin sensitivity and inflammatory process. In sum, bone may be accepted as an endocrine gland.