Índice de Robson: riesgo de cesárea en un centro de primer nivel en México / Robson index, c-section risk in a first level center in Mexico

Resumen OBJETIVO: Determinar, conforme al Índice de Robson, la tasa de cesáreas en pacientes atendidas, en un periodo de nueve meses, en el Centro de Investigación Materno-Infantil del Grupo de Estudios al Nacimiento. MATERIALES Y MÉTODOS: Estudio retrospectivo, transversal, descriptivo y monocéntrico efectuado en pacientes embarazadas atendidas en el Centro de Investigación Materno Infantil del Grupo de Estudios al Nacimiento, (CIMIGen) que finalizaron el embarazo por cesárea y en quienes se utilizó el índice de Robson para su clasificación. Parámetros de estudio: indicaciones de la cesárea, riesgo de pérdida del bienestar fetal, alta de progresión del trabajo de parto, falla en la inducción del trabajo de parto, macrosomía, periodo intergenésico corto (menos de 18 meses). RESULTADOS: Se obtuvieron 569 pacientes de las que 228 finalizaron el embarazo mediante cesárea y 341 por parto, lo que representó una tasa de cesáreas del 39.9%. Al aplicar el método de clasificación de Robson, los grupos con mayor contribución relativa a la tasa global de cesáreas fueron: grupo 1 (17.62%), grupo 2, subdividido en sus dos categorías: 2a con 19.38% y 2b 17.18%; y el grupo 5.1 (22.91%) y grupo 5.2 (3.96%). Las principales indicaciones de cesárea fueron: 1) riesgo de pérdida del bienestar fetal (18.9%), 2) falta de progresión del trabajo de parto (16.7%), 3) falla en la inducción del trabajo de parto (11.1%), 4) macrosomía (7.2%) y 5) periodo intergenésico corto (7.2%). CONCLUSIONES: El índice de Robson señaló a los grupos 1, 2 y 5 como los mayores contribuyentes a la tasa de cesáreas en CIMIGen. Esta tendencia, grupos 1 y 2 con porcentajes elevados, también se observa en otros centros de atención en México, lo que pudiera indicar una práctica de atención obstétrica que debe revisarse. Esto también se ve en otros países, aunque los porcentajes son distintos pero siguen siendo considerables en los grupos 1, 2 y 5.

Abstract OBJECTIVE: To determine, according to the Robson Index, the caesarean section rate in patients attended, over a period of nine months, at the Maternal and Infant Research Centre of the Childbirth Studies Group. MATERIALS AND METHODS: Retrospective, cross-sectional, descriptive, single-centre study carried out in pregnant patients attended at the Maternal and Infant Research Centre of the Childbirth Study Group (CIMIGen) who terminated gestation by caesarean section and in whom the Robson index was used for classification. Study parameters: indications for caesarean section, risk of loss of fetal well-being, high labour progression, failure of labour induction, macrosomia, short inter-gestational period (less than 18 months). RESULTS: We obtained 569 patients of whom 228 terminated pregnancy by caesarean section and 341 by delivery, representing a caesarean section rate of 39.9%. Applying Robson's classification method, the groups with the highest relative contribution to the overall caesarean section rate were: group 1 (17.62%), group 2, subdivided into its two categories: 2a with 19.38% and 2b 17.18%; and group 5.1 (22.91%) and group 5.2 (3.96%). The main indications for caesarean section were 1) risk of loss of fetal well-being (18.9%), 2) failure of labour to progress (16.7%), 3) failure of induction of labour (11.1%), 4) macrosomia (7.2%) and 5) short inter-gestational period (7.2%). CONCLUSIONS: Robson's index pointed to groups 1, 2 and 5 as the largest contributors to the caesarean section rate at CIMIGen. This trend, groups 1 and 2 with high percentages, is also seen in other facilities in Mexico, which may indicate an obstetric care practice that needs to be reviewed. This is also seen in other countries, although the percentages are different but still considerable in groups 1, 2 and 5.

Prenatal Particulate Matter (PM) Exposure and Natriuretic Peptides in Newborns from Mexico City.

(1) Background: The aim of this study was to assess associations between particulate matter (PM) exposure and natriuretic peptide concentrations in cord blood from newborns. (2) Methods: we conducted a cross-sectional study in Mexico City with 101 pregnant women from CIMIGEN Hospital. Atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were measured in plasma from cord blood in 51 newborns by ELISA. We estimated PM exposure (PM2.5 and PM10) at first, second and third trimester of pregnancy. (3) Results: The median and interquartile range for ANP, BNP and CNP plasma concentrations were 66.71 (46.92-80.23), 98.23 (73.64-112.30) and 1129.11 (944.10-1452.02) pg/mL, respectively. PM2.5 and PM10 levels for the whole pregnancy period were 22.2 µg/m3 and 41.63 µg/m3, respectively. Employing multivariable linear regression models adjusted for maternal age, newborn sex, smoking before pregnancy, maternal occupation and newborns' length and height, we observed a 2.47 pg/mL (95%CI: -4.67, -0.27) decrease in BNP associated with PM2.5 exposure during second trimester. Adjusted for the same set of confounders, third trimester PM10 exposure was inversely associated with ANP concentrations (beta estimate: -0.90; 95% CI: -1.80, -0.03). Neither PM10 nor PM2.5 were associated with CNP at any trimester of pregnancy. (4) Conclusions: Prenatal exposure to particulate matter was associated with ANP and BNP decrease in newborns.

Metformina: interacciones moleculares, celulares y su repercusión en la Obstetricia. Revisión bibliográfica / Metformin: Cellular and molecular interactions and its' impact in obstetrics. Literature review

Resumen OBJETIVO: Identificar los mecanismos celulares más reconocidos de la metformina y su relación con patologías en Obstetricia y determinar las moléculas y vías involucradas con potencial terapéutico. METODOLOGÍA: Estudio retrospectivo efectuado con base en la búsqueda de artículos registrados en Pubmed y Cochrane publicados en inglés entre los años 2000 a 2019 que contuvieran las palabras clave (MeSH): "Metformin"; "Celular mechanisms"; "AMPK"; "LKB1"; "Gestational diabetes", "Abortion" y "Preeclampsia". RESULTADOS: Se encontraron 1750 artículos que contenían las palabras clave de búsqueda; al final solo se analizaron 57. En estos se concluye que la intervención con este fármaco inhibe el complejo I de la cadena respiratoria mitocondrial, con repercusión en varios procesos celulares. La diabetes gestacional, el aborto y la preeclampsia se consideraron por su incidencia y relevancia obstétrica, y por la indicación de la metformina en su tratamiento. Se identificaron los mecanismos involucrados en el efecto colateral gastrointestinal y la asociación con los mecanismos celulares influidos por la metformina. En los padecimientos obstétricos se identificaron los procesos metabólicos para tratamiento común, la diabetes gestacional fue la más identificada por la experiencia en diabetes mellitus. CONCLUSIONES: Si bien la metformina tiene una indicación clara en pacientes con diabetes gestacional, los resultados son insuficientes para aborto; en preeclampsia los mecanismos intervenidos pueden tener mayor potencial terapéutico y preventivo.

Abstract OBJECTIVE: Identify the most recognized cellular mechanisms and their relations to obstetric pathology, determining molecular pathways for potential therapeutic use. METHODOLOGY: After a bibliographical search done in Pubmed and Cochrane database of MeSH terms: "metformin", "cellular mechanisms", "AMPK", "LKB1", "gestational diabetes", "abortion", "preeclampsia", in the periods comprehending 2000 through 2019, a total of 49 references were selected, on the basis of the criteria established by the objective of this review. RESULTS: With 49 selected references, we found that metformin regulates adenosine monophosphate protein kinase (AMPK) and LKB1, both who which participate in metabolic mechanisms, activating second messengers who stimulate or inhibit processes like gluconeogenesis, steroid and protein synthesis and cellular growth. This drug actually acts by inhibiting complex I of the mitochondrial respiration process, impacting various cell functions. Gestational diabetes, abortion and preeclampsia are three obstetric pathologies selected due to their incidence and relevance, as well as the fact that metformin is being used for their treatment. We also identified the mechanisms for gastrointestinal symptoms where OCT-1, PMAT and 5-HT are involved and may be therapeutic targets. The association of cell mechanisms influenced by metformin are part of various metabolic pathways, being the ones in gestational diabetes the most, well known due to experience with diabetes mellitus. CONCLUSIONS: Although metformin has a clear role in gestational diabetes, results are insufficient to identify its' role in abortion. As for preeclampsia, the mechanisms identified have a greater preventive and therapeutic potential.

Complex Laparoscopic Myomectomy with Severe Adhesions Performed with Proper Preventive Measures and Power Morcellation Provides a Safe Choice in Certain Infertility Cases.

Laparoscopic myomectomy offers a real benefit to infertile patients with uterine fibroids and peritoneal adhesions. The procedure requires a skilled surgeon and laparoscopy technique to minimize adhesion formation and other proven benefits. Restrictions arise since this procedure requires power morcellation for fibroid tissue extraction. Two years ago, the Food and Drug Administration in the United States of America (FDA) issued the alert on power morcellation for uterine leiomyomas, addressing the risk of malignant cell spreading within the abdominal cavity (actual risk assessment from 1 in 360 to 1 in 7400 cases). We review a 30-year-old female, without previous gestations, hypermenorrhea, intermenstrual bleeding, and chronic pelvic pain. Transvaginal ultrasound reports multiple fibroids in the right portion of a bicornuate uterus. Relevant history includes open myomectomy 6 years before and a complicated appendectomy, developing peritonitis within a year. Laparoscopy revealed multiple adhesions blocking uterine access, a bicornuate uterus, and myomas in the expected site. Myomectomy was performed utilizing power morcellation with good results. FDA recommendations have diminished this procedure's selection, converting many to open variants. This particular case was technically challenging, requiring morcellation, and safety device deployment was impossible, yet the infertility issue was properly addressed. Patient evaluation, safety measures, and laparoscopy benefits may outweigh the risks in particular cases as this one.

Robotics in Gynecology: Why is this Technology Worth Pursuing?

Robotic laparoscopy in gynecology, which started in 2005 when the Da Vinci Surgical System (Intuitive Surgical Inc) was approved by the US Food and Drug Administration for use in gynecologic procedures, represents today a modern, safe, and precise approach to pathology in this field. Since then, a great deal of experience has accumulated, and it has been shown that there is almost no gynecological surgery that cannot be approached with this technology, namely hysterectomy, myomectomy, sacrocolpopexia, and surgery for the treatment of endometriosis. Albeit no advantages have been observed over conventional laparoscopy and some open surgical procedures, robotics do seem to be advantageous in highly complicated procedures when extensive dissection and proper anatomy reestablishment is required, as in the case of oncologic surgery. There is no doubt that implementation of better logistics in finance, training, design, and application will exert a positive effect upon robotics expansion in gynecological medicine. Contrary to expectations, we estimate that a special impact is to be seen in emerging countries where novel technologies have resulted in benefits in the organization of health care systems.

[Diagnosis of molar pregnancy by hysteroscopy]. / Diagnóstico de embarazo molar por histeroscopia.

BACKGROUND: Gestational trophoblastic disease has a high incidence worldwide. Proper pre-evacuation diagnosis must be performed due to the risk of malignant complications associated with hydatidiform moles. Diagnosis of early molar pregnancies might be elusive due to atypical clinical manifestations and inconclusive ultrasonographic findings. OBJECTIVE: Report on the efficiency and precision by hysteroscopy for the diagnosis of molar pregnancy in one particular case. CLINICAL CASE: Thirty-year old woman, 5.6-week pregnant, suffering from pelvic pain, uterine bleeding and high concentrations of human chorionic gonadotropin beta fraction (beta-hCG). Ultrasonography suggested inconclusively either a hematoma or a gestational sac so that further evaluation by hysteroscopy had to be performed in order to reach a proper diagnosis. RESULTS: Hysteroscopic evaluation provided conclusive diagnostic images of hydropic degeneration of the chorionic villi. Histopathological evaluation confirmed a molar pregnancy. The mole was removed by uterine curettage and beta-hCG tests followed. CONCLUSIONS: Hysteroscopy is a useful tool for diagnostic protocol in case of early atypical molar pregnancy.

[Family planning methods based on fertility awareness]. / Métodos de planificación familiar basados en el conocimiento de la fertilidad.

The desire to limit fertility is recognized both by individuals and by nations. The concept of family planning is based on the right of individuals and couples to regulate their fertility and is based in the area of health, human rights and population. Despite the changes in policies and family planning programs worldwide, there are large geographic areas that have not yet met the minimum requirements in this regard, the reasons are multiple, including economic reasons but also ideological or religious. Knowledge on the physiology of the menstrual cycle, specifically ovulation process has been further enhanced due to the advances in reproductive medicine research. The series of events around ovulation are used to detect the "fertile window", this way women will look for the possibility of postponing their pregnancy or actually start looking for it. The aim of this article is to review the current methods of family planning based on fertility awareness, from the historical methods like the core temperature determination and rhythm, to the most popular ones like the Billings ovulation method, the Sympto-thermal method and current methods like the two days, and the standard days method. There are also mentioned methods that require electronic devices or specifically computer designed ones to detect this "window of fertility". The spread and popularity of these methods is low and their knowledge among physicians, including gynecologists, is also quite scarce. The effectiveness of these methods has been difficult to quantify due to the lack of well designed, randomized studies which are affected by small populations of patients using these methods. The publications mention high effectiveness with their proper use, but not with typical use, what indicates the need for increased awareness among medical practitioners and trainers, obtaining a better use and understanding of methods and reducing these discrepancies.

[Robotics in gynecology. Background, feasibility and applicability]. / La robótica en Ginecología. Antecedentes, viabilidad y conveniencia.

BACKGROUND: Robotic surgery is a technology that emerged from the fusion and improvement of laparoscopy, robotics and telepresence. All these three technologies underwent a long experimentation process in which several applications and innovations were tested until the only system approved for use in humans was developed: the Da Vinci system by Intuitive Surgical Inc. Gynecology, being one of the pioneer branches of Medicine involved in the development of laparoscopy, is one of the fields with the greatest possibilities for robotics, which offers great diversity of applications in hysterectomies, myomectomies, endometriosis, and in the fields of urogynecology and, most importantly, oncology. There are no publications in Mexico with a proper description of the clinical experience with gynecologic robotic surgery, though a great amount of clinical experience has been accumulated in institutions that already have such equipment. A serious evaluation of the cost-benefit ratio is required because of the high cost of this technology. OBJECTIVE: Evaluate and analyze the accumulated experience on this technology of foreign institutions in order to assess the benefits, cost and effectiveness of robotic surgery. CONCLUSION: The key to the optimal use of robotic technology is to diminish costs and speed the learning curve, and this implies the entry of other systems into the market as well as institutions with a high volume of patients and determined to invest in a highly trained and skilled surgical team. In order to recommend its implementation in our country an assessment of the efficiency and advantages of robotic technology considering institutional needs is mandatory.

Resolución laparoscópica de translocación abdominal de dispositivo intrauterino: Reporte de un caso / Laparoscopic removal of an intra-abdominal translocated intrauterine device: Case report

A partir de que Richter R, en 1909, realizó la primera publicación sobre el uso de dispositivos intrauterinos con fines anticonceptivos, la forma, los materiales, las indicaciones, así como las contraindicaciones han evolucionado hasta convertirse en el método de planificación familiar más usado en el mundo. El riesgo de perforación durante la inserción es bajo; sin embargo, ha sido referida. En la literatura se ha descrito el uso de la laparoscopia para la extracción de dispositivos intrauterinos migrados a cavidad abdominal. En la presente publicación se reporta el caso clínico de una mujer de 29 años de edad, con antecedente de colocación de dispositivo intrauterino, dos años previos, por vía vaginal sin complicación aparente; comenta sólo dolor de cólico posterior a la colocación que va cediendo a analgésicos vía oral no especificados, sin sintomatología hasta la fecha. Acude a revisión y realización de citología cervical donde no se encuentran hilos guía del dispositivo intrauterino. Mediante radiografía simple de abdomen y bajo fluoroscopia se determina la localización intraabdominal del testigo radiopaco del dispositivo, es valorada por el Servicio de Cirugía General y se determina a realizar la extracción del mismo por vía laparoscópica sin complicaciones; se encontró el dispositivo con adherencias a omento mayor, sin afección aparente de órganos intraabdominales. La Organización Mundial de la Salud recomienda la extracción inmediata de los dispositivos intrauterinos que han migrado. La migración del dispositivo intrauterino a la cavidad abdominal es una complicación poco frecuente, y la presentación como hallazgo en pacientes asintomáticas es aún menos frecuente; en una revisión sistemática de la literatura, Richdeep S y cols. valoraron 49 artículos en los que encontraron 179 casos de manejo laparoscópico, reportando al omento como el sitio más frecuente de localización (26.7%). La relevancia del presente caso radica en la presentación asintomática dos años posteriores a su inserción, la ruta diagnóstica utilizando radiografías simples y fluoroscopia, así como la extracción sin complicaciones y con excelente resultado, vía laparoscópica.

Since Richter R. in 1909 performed the first publication on the use of intrauterine devices; materials, forms, indications and contraindications of these have evolved to become the method most widely used family planning in the world. Although the risk of perforation during insertion is low, it exists. The literature has described the use of laparoscopy for removal of intrauterine devices migrated to the abdominal cavity. Case report: 29 years old woman who two years before suffers colic pain posterior to application of an intrauterine device with no complications, and diminishes with the use of unspecified analgesics, and stays asymptomatic to date. She attended a review, and underwent to cervical cytology, during the procedure, was impossible to see the strings of the intrauterine device. Plain abdominal radiography and fluoroscopy were done to determine the location of the radiopaque intraabdominal witness. Assessed by the General Surgery Service we determined extraction of the device by laparoscopy and was done without any complication. Findings: strong omentum adhesions to the device, but no apparent damage to other abdominal organs. The World Health Organization recommends the immediate removal of intrauterine devices that have migrated. The migration of the intrauterine devices into the abdominal cavity is a rare complication, and the presentation as an incidental finding in asymptomatic patients is even less common, a systematic review of literature, Richdeep S. et al, evaluated 49 items found 179 cases of laparoscopic management reporting the omentum as the most common site of localization (26.7%). The relevance of this case lies in the asyntomatic presentation two years after insertion, the diagnostic route using radiographs and fluoroscopy, and extraction without complications and with excellent results laparoscopically.

[Comparison of laparoscopic vs. laparotomy treatment in ovarian teratomas]. / Comparación del tratamiento laparoscópico vs laparotomía en teratomas ováricos.

BACKGROUND: Benign cystic teratoma is one of the most common benign tumors of the ovary, according to international series represents between 44 and 62% of all ovarian tumors diagnosed in women younger than 40 years. OBJECTIVES: To evaluate and compare the efficacy and safety between laparoscopy and laparotomy in the management of ovarian teratomas, as well as the recurrence between both techniques. MATERIALS AND METHOD: Retrospective, clinical series study involving 169 cases of ovarian teratomas operated at the Instituto Nacional de Perinatología Isidro Espinosa de los Reyes in the period comprehended between 2000-2008. The cases were divided into the ones solved by laparoscopy, corresponding to group 1 (102 cases) and 67 cases solved by laparotomy, corresponding to group 2. RESULTS: Group 1 (laparoscopic approach) consisted of 102 patients (60.3%), and group 2 (laparotomy approach) had 67 patients (39.7%). Surgical bleeding: 55.7 +/- 21.4 mL vs. 91.6 +/- 29.2 mL (p < 0.0001), hospital stay: 1.6 +/- 0.57 vs. 2.7 +/- 0.42 days (p < 0.0001), surgical time: 110.3 +/- 27.2 vs. 83.6 +/- 26.9 minutes (p < 0.0001), teratoma size: 7.2 +/- 2.3 vs. 11.5 +/- 4.2 cm (p < 0.0001) in groups 1 and 2, respectively. Teratoma rupture had 57.8% incidence (59 cases) in group 1, and 16.4% in group 2 (11 cases). Laparoscopy was a risk factor for broken open for ovarian cyst (OR: 6.9; CI 95%: 3.3-14.8). Not a single case was complicated by chemical peritonitis in any study group. CONCLUSIONS: Laparoscopic approach to teratomas is a safe and efficient procedure, it does not increase complications in comparison to the laparotomy approach; it presents less bleeding and short hospital stay, offering a quick recovery.

[Total laparoscopic hysterectomy: descriptive study of institutional experience with 198 cases]. / Histerectomía total laparoscópica: estudio descriptivo de la experiencia institucional con 198 casos.

BACKGROUND: Total laparoscopic hysterectomy is a useful surgery in current gynecology, specially, in cases where abdominal access is indicated. Total laparoscopic hysterectomy performance has increased in recent years. OBJECTIVE: To analyze the clinical characteristics and surgical variables of patients undergoing laparoscopic total hysterectomy for benign disease, performed at the Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes, between 2007 and 2009. MATERIAL AND METHOD: Retrospective, longitudinal and descriptive study. Medical records of all patients with a noncancer diagnosis underwent laparoscopic hysterectomy were reviewed, at the Instituto Nacional de Perinatologia, between January 1, 2007 and December 31, 2009. RESULTS: 594 hysterectomies were performed, of which 37.3% were by laparoscopic surgery, within these 89.1% were through the total laparoscopic hysterectomy technique. Surgical indications were 58.6% for fibroids, 23.2% abnormal uterine bleeding and 18.2% for adenomiosis. Studied variables revealed an average surgical time of 139 + 66.9 min (range: 75-225 min), average surgical bleeding of 119.7 +/- 60.5 mL (50-350 mL), average uterine longitude of 12.4 +/- 2 cm (8-16 cm), average uterine weight 222.7 +/- 113.8 g (90-860 g), and average hospital stay of 2.3 +/- 0.5 days (2-4 days), all of these results within the range reported in the literature. CONCLUSIONS: Previous surgical interventions were observed as complications risk factors, 162 (81%) patients had previous surgeries, 29% with 2 c-sections, 20% with 3 or more and 27% had other non-obstetrical interventions. This technique is safe and reliable, it does not replace the vaginal access and with adequate training and equipment it may be performed in an efficient manner with satisfactory results in our population.

[Endometriosis: physiopathology and investigation lines (part two)]. / Endometriosis: fisiopatología y líneas de investigación (segunda parte).

Sampson's menstrual reflux theory (1927) is widely accepted as an explanation of endometriosis physiopathology, it proposes five basic necessary processes to its development: adhesion, invasion, recruitment, angiogenesis and proliferation. Several factors and physiologic processes are necessary for the survival and growth of endometrial tissue. Clinical manifestations of these disease are: dysmenorrhoea, dyspareunia, and peritoneal adhesions, that with other findings reveal an inflammatory process that requires cytokines, macrophages, NK cells, lymphocytes and prostaglandins whose qualitative functions may be compromised or may contribute to the peripheral generation of estrogens. Angiogenesis benefits the development of these endometrial tissue foci and probably stimulates several vascular growth factors, and sexual steroids. Endocrine factors are capital for this entity, as is demonstrated by the presence of estrogen receptors in macrophages, fibroblasts and endometrium among others, as well as the clinical symptoms control trough the blockage of the hypothalamus-pituitary-ovary axis. Studies on the genetic and antioxidant factors have revealed key points that may be helpful in determining a proper diagnosis and treatment for endometriosis.

[Endometriosis: physiopathology and investigation trends (first part)]. / Endometriosis: fisiopatología y líneas de investigación (primera parte).

Until today endometriosis continues to be a diagnostic challenge since the only way to confirm a diagnosis, based on clinical criteria, is through direct visualization of the endometriosis lesions. This has a direct impact in the development of proper statistics on the incidence and prevalence of endometriosis. Current research has been focused on the basis of the Retrograde Menstruation theory, establishing the involvement of various biochemical, immunologic and molecular factors within the physiopathology of endometriosis. The development of endometriosis has been divided into 5 basic processes: adhesion, invasion, recruiting, angiogenesis and proliferation, here, we have revised the first two due to the importance they potentially contain with regards to diagnosis and therapy. Research on adhesion has led to studies on the peritoneal epithelium structure, the role of integrins, intercellular adhesion molecules (ICAM), cadherins and hyaluronic acid; invasiveness has led to the study of the tumor necrosis factor alpha (TNF-alpha), various protocols on metaloproteinases and their inhibitors as well as their interactions and response to sexual steroids, tumor growth factor beta (TGF-beta), interleukins and metalloproteinase polymorphisms. These advances have been crucial, though various observations leads us to believe that the etiology is multifactorial, there are factors whose antagonists, inhibitors or suppressors may actually have a role as molecular markers or therapeutic agents of endometriosis.

Regulation of G protein-coupled receptor trafficking by inefficient plasma membrane expression: molecular basis of an evolved strategy.

Despite the prevalence of G protein-coupled receptors as transducers of signals from hormones, neurotransmitters, odorants, and light, little is known about mechanisms that regulate their plasma membrane expression (PME), although misfolded receptors are recognized and retained by a cellular quality control system (QCS). Convergent evolution of the gonadotropin-releasing hormone (GnRH) receptor (GnRHR) progressively decreases inositol phosphate production in response to agonist, validated as a measure of PME of receptor. A pharmacological chaperone that optimizes folding also increases PME of human, but not of rat or mouse, GnRHR because a higher percentage of human GnRHRs are misfolded structures due to their failure to form an apparent sulfhydryl bridge, and they are retained by the QCS. Bridge formation is increased by deleting (primate-specific) Lys191. In rat or mouse GnRHR that lacks Lys191, the bridge is non-essential and receptor is efficiently routed to the plasma membrane. Addition of Lys191 alone to the rat sequence did not diminish PME, indicating that other changes are required for its effects. A strategy, based on identification of amino acids that both 1) co-evolved with the Lys191 and 2) were thermodynamically unfavorable substitutions, identified motifs in multiple domains of the human receptor that control the destabilizing influence of Lys191 on a particular Cys bridge, resulting in diminished PME. The data show a novel and underappreciated means of posttranslational control of a G protein-coupled receptor by altering its interaction with the QCS and provide a biochemical explanation of the basis of disease-causing mutations of this receptor.

[Ovarian denervation and polycystic ovary]. / Denervación y poliquistosis ováricas.

BACKGROUND: Ovarian inervation is limited to the superior pedicle and ovarian artery to loose itself within the gonadal smooth muscle. Hence, it is far from clear how is it that the ovary preserves its communication with hypothalamic and pituitary structures for feedback regulation. There is a lack of precision concerning structures and mechanisms involved in the genesis of polycystic disease. OBJECTIVE: To know the role of inervation associated to hormone stimuli in developing polycystic ovaries. MATERIAL AND METHODS: Groups of Sprague Dawley rats were studied: group 1, whom received cornoil (vehicle) served as controls; group 2 had estradiol valerianate (EV) and group 3 was exposed to phenol for denervation and also received estradiol valerianate (EV). After sacrifice, ovaries were exposed and saved in a formol solution until preparation and staining with hematoxilin-eosin and for immunochemical reaction using specific monoclonal antibodies for nerve tissue (PS-100 & GFAP). RESULTS: Biologic response was considered when follicle dilation was seen under microscopy evaluation. The ovaries with higher follicle development belonged to group 2 (EV) while preserving intrinsic follicular nervous activity as shown by a positive immunoreaction to PS-100 & GFAP. Those denervated and exposed to EV (group 3) did not show significant changes in follicular size resembling controls. CONCLUSIONS: The presence of neural activity is vital for development of cysts and the neural mechanisms involved seemed to lie within the ovarian cells.