[Prognostic scale for in-hospital mortality in patients with COVID-19 viral pneumonia].

Background: The COVID-19 pandemic represented a challenge in medical care. A tool would be very useful to establish the prognosis of in-hospital death that is reliable and can be applied to the Mexican population entitled to the IMSS.

Objective: To propose a prognostic scale to stratify patients with viral pneumonia COVID-19 in the emergency services.

The motility of Entamoeba histolytica: finding ways to understand intestinal amoebiasis.

The pathogenic amoeba Entamoeba histolytica is able to migrate within various compartments of the human body. The present article reviews progress in understanding the mechanisms of cell motility in E. histolytica during human intestinal invasion and, in particular, how the three-dimensional characteristics of the environment regulate the parasite's behaviour.

Role of Cysteine Residues in the Carboxyl-Terminus of the Follicle-Stimulating Hormone Receptor in Intracellular Traffic and Postendocytic Processing.

Posttranslational modifications occurring during the biosynthesis of G protein-coupled receptors include glycosylation and palmitoylation at conserved cysteine residues located in the carboxyl-terminus of the receptor. In a number of these receptors, these modifications play an important role in receptor function and particularly, in intracellular trafficking. In the present study, the three cysteine residues present in the carboxyl-terminus of the human FSHR were replaced with glycine by site-directed mutagenesis.

Effects of the lifestyle habits in breast cancer transcriptional regulation.

Through research carried out in the last 25 years about the breast cancer etiology, it has been possible to estimate that less than 10 % of patients who are diagnosed with the condition are carriers of some germline or somatic mutation. The clinical reports of breast cancer patients with healthy twins and the development of disease in women without high penetrance mutations detected, warn the participation more factors in the transformation process. The high incidence of mammary adenocarcinoma in the modern woman and the urgent need for new methods of prevention and early detection have demanded more information about the role that environment and lifestyle have on the transformation of mammary gland epithelial cells.

Mutations in G protein-coupled receptors that impact receptor trafficking and reproductive function.

G protein coupled receptors (GPCRs) are a large superfamily of integral cell surface plasma membrane proteins that play key roles in transducing extracellular signals, including sensory stimuli, hormones, neurotransmitters, or paracrine factors into the intracellular environment through the activation of one or more heterotrimeric G proteins. Structural alterations provoked by mutations or variations in the genes coding for GPCRs may lead to misfolding, altered plasma membrane expression of the receptor protein and frequently to disease. A number of GPCRs regulate reproductive function at different levels; these receptors include the gonadotropin-releasing hormone receptor (GnRHR) and the gonadotropin receptors (follicle-stimulating hormone receptor and luteinizing hormone receptor), which regulate the function of the pituitary-gonadal axis.

Normal testicular function without detectable follicle-stimulating hormone. A novel mutation in the follicle-stimulating hormone receptor gene leading to apparent constitutive activity and impaired agonist-induced desensitization and internalization.

Activating mutations in the follicle-stimulating hormone (FSH) receptor (FSHR) gene are rarely detected due to the absence of a clearly defined phenotype, particularly in men. We here report the biochemical features of a novel mutation in the first extracellular loop of the FSHR. The mutation (N431I) was detected in an asymptomatic man exhibiting normal spermatogenesis, suppressed serum FSH, and normal or elevated levels of biochemical markers of FSH action.

Pharmacoperones: a new therapeutic approach for diseases caused by misfolded G protein-coupled receptors.

G Protein-coupled receptors (GPCRs) are cell membrane proteins that recognize specific chemical signals such as drugs and hormones and transduce these signals into cellular responses by activating G-proteins. As is the case for all newly synthesized proteins, GPCRs are subjected to conformational scrutiny at the endoplasmic reticulum prior to processing and trafficking to the cell surface membrane. Because of this stringent quality control screening mechanism, mutations that result in protein misfolding frequently lead to retention in the endoplasmic reticulum, aggregation or other misrouting and, eventually, to disease.

Biochemical mechanism of pathogenesis of human gonadotropin-releasing hormone receptor mutants Thr104Ile and Tyr108Cys associated with familial hypogonadotropic hypogonadism.

The pathogenic mechanisms whereby the Thr104Ile and Tyr108Cys mutations in the gonadotropin-releasing hormone receptor (GnRHR) gene cause hypogonadotropic hypogonadism in humans are unknown. Transient expression of Thr104Ile and Tyr108Cys mutants in COS-7 cells revealed that both GnRHR mutants neither bind nor respond to agonist. Removal of Lys191 rescued function of both mutants, while addition of a carboxyl-terminal targeting sequence only rescued function of the Thr104Ile mutant.

[Comparison of climacteric syndrome symptoms among perimenopausal women from Mexico City and one Zapotec community of Oaxaca, Mexico].

Background: Climacteric syndrome accompanies the menopause and it has been studied in different cultures, with different results among them.

Objective: To compare the differences in the presentation of the climacteric syndrome among urban and rural women.

Material And Method: A transverse, study was carried out, in which climacteric symptoms were evaluated with the previously validated modified SUMEVA scale in two groups of perimenopausal women.

Dominant negative effects of human follicle-stimulating hormone receptor expression-deficient mutants on wild-type receptor cell surface expression. Rescue of oligomerization-dependent defective receptor expression by using cognate decoys.

Current evidence indicates that G protein-coupled receptors form dimers that may affect biogenesis and membrane targeting of the complexed receptors. We here analyzed whether expression-deficient follicle-stimulating hormone receptor (FSHR) mutants exert dominant negative actions on wild-type FSHR cell surface membrane expression. Co-transfection of constant amounts of wild-type receptor cDNA and increasing quantities of mutant (R556A or R618A) FSHR cDNAs progressively decreased agonist-stimulated cAMP accumulation, [(125)I]-FSH binding, and plasma membrane expression of the mature wild-type FSHR species.

Reproductive axis function and gonadotropin microheterogeneity in a male rat model of diet-induced obesity.

Obesity causes complex metabolic and endocrine changes that may lead to adverse outcomes, including hypogonadism. We herein studied the reproductive axis function in male rats under a high-fat diet and analyzed the impact of changes in glycosylation of pituitary LH on the bioactivity of this gonadotropin. Rats were fed with a diet enriched in saturated fat (20% of total calories) and euthanized on days 90 or 180 of diet.

Targeting of G protein-coupled receptors to the plasma membrane in health and disease.

G protein-coupled receptors (GPCRs) are cell surface membrane proteins that recognize specific signals (ligands) from an immense number of chemically diverse substances. These receptors act as signal transducers for messages carried by external, systemic, or local stimuli. As complex molecular structures, which must attain specific shapes, newly synthesized GPCRs are subjected to conformational scrutiny at the endoplasmic reticulum level before their passage to the plasma membrane.

Conformational effects of Lys191 in the human GnRH receptor: mutagenesis and molecular dynamics simulations studies.

In the present study, we analyzed the role of Lys191 on function, structure, and dynamic behavior of the human GnRH receptor (hGnRHR) and the formation of the Cys14-Cys200 bridge, which is essential for receptor trafficking to the plasma membrane. Several mutants were studied; mutants lacked either the Cys14-Cys200 bridge, Lys191 or both. The markedly reduced expression and function of a Cys14Ser mutant lacking the 14-200 bridge, was nearly restored to wild-type/DeltaLys191 levels upon deletion of Lys191.

[Relation between hormonal therapy and tibolone with SERMs in postmenopausal women's myomes growth].

Myomas (both leiomyomas and fibromas) are the most frequent benign uterine tumors in women, they can be found in 77% of hysterectomy specimens. There are reports that previous hormonal therapy (estrogen-progestin), more than five years, is associated with high risk (fourfold higher) of leiomyomas. A study in patients without myomas demonstrated this type tumors production (5%) after receiving transdermical-oral hormonal combination during 24 months, and they were absent in patients with only oral therapy.

[Comparison between clinical and ultrasonographic measurements to estimate fetal weight during labor: a new clinical calculation formula].

Background: Fetal weight estimation is an important parameter in decision making during labor to avoid delivery complications.

Objectives: To evaluate the reliability of clinical and ultrasonographic measurements in fetal weight estimation during active delivery, as well as to define which is the best method for calculate it.

Material And Methods: Study of 115 healthy pregnant women during labor.

[Critical reading aptitude of clinical research texts in teaching specialist doctors].

Background: Learning can be divided in two types: the unconscious learning and the significant learning. The critical aptitude for reading clinical research articles is a learning experience that reflects the doctor's active participation in article reading.

Objective: To know the degree of aptitude for critical reading of clinical research articles in specialists under training.

Modeling and molecular dynamics simulation of the human gonadotropin-releasing hormone receptor in a lipid bilayer.

In the present study, a model for the human gonadotropin-releasing hormone receptor embedded in an explicit lipid bilayer was developed. The final conformation was obtained by extensive molecular dynamics simulations of a homology model based on the bovine rhodopsin crystal structure. The analysis of the receptor structure allowed us to detect a number of specific contacts between different amino acid residues, as well as water- and lipid-mediated interactions.

Multiple facets of follicle-stimulating hormone receptor function.

Follicle-stimulating hormone (FSH) is a glycoprotein hormone produced by the anterior pituitary gland. This gonadotropin plays an essential role in reproduction. Its receptor (FSHR) belongs to the superfamily of G protein-coupled receptors (GPCR), specifically the family of rhodopsin-like receptors.

Functional and structural roles of conserved cysteine residues in the carboxyl-terminal domain of the follicle-stimulating hormone receptor in human embryonic kidney 293 cells.

The carboxyl-terminal segment of G protein-coupled receptors has one or more conserved cysteine residues that are potential sites for palmitoylation. This posttranslational modification contributes to membrane association, internalization, and membrane targeting of proteins. In contrast to other members of the glycoprotein hormone receptor family (the LH and thyroid-stimulating hormone receptors), it is not known whether the follicle-stimulating hormone receptor (FSHR) is palmitoylated and what are the effects of abolishing its potential palmitoylation sites.

Brachial artery responses in menopausal women using tibolone.

Objective: To determine the effect of tibolone treatment on brachial artery pulsatility index (PI), resistance index (RI), and flux-mediated dilation (FMD) in postmenopausal Mexican women.

Method: The FMD, PI, and RI of the right brachial artery were measured in 19 postmenopausal women before and after they received a hyperemic stimulus, first at baseline and then following a 6-month treatment with 2.5 mg of tibolone per day.

Regulation of Clara cell secretory protein gene expression by the CCAAT-binding factor NF-Y.

Analysis of the transcriptional regulation of the Clara cell secretory protein (CCSP) gene has resulted in the characterization of several trans-acting factors that regulate the activity of this gene. However, little is known about negative regulatory elements involved in CCSP gene transcription. Using transient transfections of luciferase reporter constructs driven by various fragments of the Neotomodon CCSP (nCCSP) promoter, we identified an inhibitory region that contains an inverted CCAAT box located -225 to -221 bp upstream of the transcriptional start site.

Role of the intracellular domains of the human FSH receptor in G(alphaS) protein coupling and receptor expression.

The human (h) follicle-stimulating hormone receptor (FSHR) belongs to the superfamily of G protein-coupled receptors (GPCRs). This receptor consists of 695 amino acid residues and is preferentially coupled to the G(s) protein. This receptor is highly conserved among species (overall homology, 85%), with a 25-69% homology drop when compared to the human LH and TSH receptors.

Effects of metformin on inappropriate LH release in women with polycystic ovarian syndrome and insulin resistance.

The role of hyperinsulinaemia in neuroendocrine abnormalities in polycystic ovarian syndrome (PCOS) is controversial. The present study applied frequent blood sampling to assess the response of LH to metformin treatment in insulin-resistant women with PCOS. Thirteen predominantly overweight women with PCOS were studied before and after treatment with 1.

Genetic variation in the interleukin-8 gene promoter and vaginal concentrations of interleukin-8 are not associated with bacterial vaginosis during pregnancy.

Interleukin-8 (IL-8) may play a role in the activation of the vaginal immune system during bacterial vaginosis. However, contradictory results were obtained regarding the involvement of IL-8 in the immunological response during bacteria vaginosis. These apparently contradictory results could be due to different genetic variations of the study groups.

Functional significance of the BBXXB motif reversed present in the cytoplasmic domains of the human follicle-stimulating hormone receptor.

The minimal structural motif, BBXXB (where B represents a basic amino acid residue and X a non-basic residue), located in particular regions of the intracellular domains of cell surface membrane receptors is involved in the G protein-activating activity of a number of G protein-coupled receptors. The human FSH receptor (hFSHR) exhibits a reversed BBXXB motif (BXXBB) in the juxtamembrane region of the third intracellular loop (IL3) and the carboxyl terminus (Ctail) of the receptor; however the importance of this sequence on receptor function remains unclear. In the present study, we analyzed the effects of mutations in this structural motif on hFSHR expression, receptor-mediated effector activation and agonist-provoked receptor internalization.