von Willebrand Disease and other hereditary haemostatic factor deficiencies in women with a history of postpartum haemorrhage.

INTRODUCTION: Postpartum haemorrhage (PPH) is the main cause of maternal morbidity and mortality globally, but it is far more important in non-developed countries. PPH represents 25% of all maternal deaths worldwide. Women with von Willebrand disease (VWD) and other inherited haemorrhagic disorders are at increased risk of PPH. Our aim was to establish a probable association of severe PPH in women with a history of haemostatic abnormalities. METHODS: An observational, controlled study of adult women with a one or more episodes of severe PPH requiring treatment in an intensive care unit or >10 units of blood products during the 24-hour period after diagnosis and their controls. The tests performed were blood cell count, blood group, renal, viral, liver function and haemostatic tests, fibrinogen, activity of the plasma factors and specific test to diagnose and classify VWD. RESULTS: We included 124 women with 133 PPH events and their controls. The median age at the first event was 25.5 years old. Results were significantly different between the groups in terms of fibrinogen concentration, VWF:Ag, VWF:RCo and FVIII. A specific diagnosis was established in 69 (55.6) and 4 (3.2%) patients in the PPH group and controls, respectively. Of 61 patients with VWD, 57 had type 1, two had type 2A, and another two had type 2B. CONCLUSION: Our results show a relationship between PPH and inherited haemostatic disorders. VWD was the most frequent diagnosis. Appropriate and opportune diagnosis before pregnancy of inherited haemostatic disorders may be important to effectively prevent and treat PPH.

Effect of a natural supplement containing glucosinolates, phytosterols and citrus flavonoids on body weight and metabolic parameters in a menopausal murine model induced by bilateral ovariectomy.

OBJECTIVE: To evaluate the effect of a herbal preparation containing glucosinolates, phytosterols and citrus flavonoids (supplement) on body weight and metabolic parameters usually impaired by menopause. METHODS: A pre-clinical experimental study carried out in twenty-five Swiss strain mice (Mus musculus) randomly distributed (1:1:1:1:1 ratio) to five groups to receive for ten weeks: (1) oral gelatinized maca extract 0.5625 mg/kg/day + bilateral ovariectomy (Maca + OVX); (2) oral supplement 0.5625 mg/kg/day + bilateral ovariectomy (S1 + OVX); (3) oral supplement 1.6875 mg/kg/day + bilateral ovariectomy (S2 + OVX); (4) oral saline 100 µl/kg/day + bilateral ovariectomy (OVX); and (5) oral saline 100 µl/kg/day + sham surgery (sham). The primary endpoint was change in body weight gain from baseline to final. Secondary endpoints were uterine weight and cholesterol, triglyceride, glucose, and glucose/triglycerides index values at the end of the study. A modified intention-to-treat analysis was performed through linear regression models and using the Bonferroni method to penalized p-values by multiple comparisons. RESULTS: Twenty-three animals completed the study. There was a significant average difference in weight gain, with a greater reduction in the S2 + OVX group compared to the OVX group (difference= -3.5; 95% CI (-5.27; -1.74); p < .001). S2 + OVX group also displayed a significant average reduction of total blood cholesterol (difference: -16.94; 95% CI (-33.73; -0.15); p = .037). No significant effects of the supplement were found on other secondary endpoints. CONCLUSION: In this murine menopausal model, triple oral supplement dose resulted in an average reduction of weight gain and total cholesterol levels, suggesting that the compound could have a potential effect at regulating menopausal altered metabolism.

The regulatory effect of bromocriptine on cardiac hypertrophy by prolactin and D2 receptor modulation.

BACKGROUND: Bromocriptine, a dopamine agonist, used for the treatment of hyperprolactinemia, type 2 diabetes, ovarian hyper-stimulation syndrome, has also effects on the cardiac remodeling process, but the mechanism of action is unknown. The aim of this work was to determinate the effect during hypertrophic process through molecular mechanisms that include prolactin receptor (Prlr) and receptor of dopamine 2 (D2 r) expression. METHODS: We used a model of cardiac hypertrophy induced by an aortocaval fistula (ACF) surgery in rats. Protein concentrations of D2 r and Prlr were determined by western blotting. The treatment consisted in water (control), captopril (50 mg/kg/day), bromocriptine (3 mg/kg/day), and ACF group (n = 6 per group). RESULTS: Our results showed that bromocriptine treatment decreases the hypertrophy index. Treatment with bromocriptine increases the protein expression of Prlr and D2 r in the cardiac tissue of rats with cardiac hypertrophy. CONCLUSIONS: We concluded that bromocriptine has a protective effect on cardiac hypertrophy, and due to this effect, it may modulate the expression of Prlr and D2 r, which are involved in the development of cardiac hypertrophy.

Gram-Negative ESKAPE Bacteria Surveillance in COVID-19 Pandemic Exposes High-Risk Sequence Types of Acinetobacter baumannii MDR in a Tertiary Care Hospital.

The interruption of bacteriological surveillance due to the COVID-19 pandemic brought serious consequences, such as the collapse of health systems and the possible increase in antimicrobial resistance. Therefore, it is necessary to know the rate of resistance and its associated mechanisms in bacteria causing hospital infections during the pandemic. The aim of this work was to show the phenotypic and molecular characteristics of antimicrobial resistance in ESKAPE bacteria in a Mexican tertiary care hospital in the second and third years of the pandemic. For this purpose, during 2021 and 2022, two hundred unduplicated strains of the ESKAPE group (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii) were collected from various clinical sources and categorized by resistance according to the CLSI. An analysis of variance (ANOVA) complemented by the Tukey test was performed to search for changes in antimicrobial susceptibility profiles during the study period. Finally, the mechanisms of resistance involved in carbapenem resistance were analyzed, and the search for efflux pumps and high-risk sequence types in A. baumannii was performed by multilocus analysis (MLST). The results showed no changes in K. pneumoniae resistance during the period analyzed. Decreases in quinolone resistance were identified in E. coli (p = 0.039) and P. aeruginosa (p = 0.03). Interestingly, A. baumannii showed increases in resistance to penicillins (p = 0.004), aminoglycosides (p < 0.001, p = 0.027), carbapenems (p = 0.027), and folate inhibitors (p = 0.001). Several genes involved in carbapenem resistance were identified (blaNDM, blaVIM, blaOXA, blaKPC, blaOXA-40, and blaOXA-48) with a predominance of blaOXA-40 and the adeABCRS efflux pump in A. baumannii. Finally, MLST analysis revealed the presence of globally distributed sequence types (ST369 and ST758) related to hospital outbreaks in other parts of the world. The results presented demonstrate that the ESKAPE group has played an important role during the COVID-19 pandemic as nosocomial antibiotic-resistant pathogens and in particular A. baumannii MDR as a potential reservoir of resistance genes. The implications of the increases in antimicrobial resistance in pathogens of the ESKAPE group and mainly in A. baumannii during the COVID-19 pandemic are analyzed and discussed.

Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN. METHODS: This study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment. DISCUSSION: This study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05521737 Registered on 30 August 2022. International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b].

Dermatoscopic Patterns in Childhood Vitiligo and Their Association With Reflectance Confocal Microscopy Findings.

INTRODUCTION: The diagnosis of vitiligo is mainly based on clinical findings. However, dermoscopy or reflectance confocal microscopy (RCM) could be useful for assessing its progression (stability, pigmen-tation, or depigmentation). OBJECTIVES: To evaluate the correlation of dermatological findings by dermoscopy and RCM in pediatric vitiligo. METHODS: We conducted a cross-sectional, descriptive, and analytical clinical study. Pediatric patients with vitiligo of both sexes, aged > 1 year and < 18 years, with all spectrums of the disease were includ-ed. Vitiligo lesions were evaluated clinically, by dermoscopy, and microscopy. RESULTS: A total of 40 patients with vitiligo were included. Eight dermoscopic patterns were found: reduced/absent pigment network, perifollicular pigmentation, trichromic, tapioca sago, perifollicular depigmentation, starburst, leukotrichia, and erythema. Skin with a normal pigment network showed complete dermal papillary rings and half-rings. Skin with reduced/absent pigment network also had an absence of papillary rings or only showed half-rings and was more common in unstable vitiligo. The trichrome pattern only showed half-rings. The Tapioca sago pattern showed complete papillary rings and appeared in younger patients. Perifollicular pigmentation showed half-rings and complete rings and did not show associations. The diffuse borders did not present complete papillary structures. It was found that vitiligo duration time of fewer than 24 months (Odds Ratio 4.56, CI 1.09-18.99) and absent papillary rings (OR 2.75, CI 1.01-7.51) are associated with unstable prognosis. CONCLUSIONS: Certain dermatoscopic and microscopic findings, such as the reduction/absence of the pigment network, tapioca sago pattern, and absence of papillary rings, can be used to assess the stabil-ity of the disease and provide insight into the clinical behaviour of vitiligo.

Mortality and Survival Factors in Patients with Moderate and Severe Pneumonia Due to COVID-19.

During the pandemic, some mortality-related factors were age, sex, comorbidities (obesity, diabetes mellitus, and hypertension), recovery time, hospitalizations, and biochemical markers. The present work aimed to identify the mortality and survival factors in adults with moderate and severe pneumonia due to COVID-19 during the first and second waves of the pandemic in Mexico at a third-level hospital (High-Specialty Regional Hospital of Ixtapaluca (HRAEI), Ixtapaluca, Estado de Mexico, Mexico). A database was generated using information from the electronic clinical records of patients hospitalized from December 2021 to August 2022. Survival analysis was performed associating age, sex, longer recovery times, and some drugs. The risk factors found were age in the patients between 40 and 60 years (OR = 1.70), male sex (OR = 1.53), the presence of comorbidities (OR = 1.66) and hypertension (OR = 2.19), work occupation (construction workers OR = 5.22, factory workers OR = 3.13, unemployed OR = 2.93), the prehospital use of metamizole sodium (OR = 2.17), cough (OR = 1.73), and in-hospital oxygen therapy (reservoir mask OR = 6.6). The survival factors found in this study were working in the healthcare field (OR = 0.26), the prehospital use of certain medications (paracetamol OR = 0.65, dexamethasone OR = 0.55, and azithromycin OR = 0.47), presenting ageusia (OR = 0.5) and hyporexia (OR = 0.34), and the time using in-hospital oxygen therapy (device 1 OR = 0.72). Prehospital treatment needs to be reevaluated as dexamethasone and azithromycin proved to be protective factors. Likewise, providing aggressive oxygen therapy during hospital admission decreased mortality risk.

Molecular Characterization of Bacterial Agents Causing External Ocular Infections Isolates of Patients in a Third Level Hospital.

Empirical use of antibiotics in the treatment of eye infections leads to bacterial pathogens becoming resistant to antibiotics; consequently, treatment failure and eye health complications occur. The aim of this study was to describe the phenotype and genotype of the resistance and adherence of bacterial agents causing eye infections in patients at Hospital Juárez de México. An observational, prospective, cross-sectional, and descriptive study was carried out in patients with signs and symptoms of ocular infection. Bacterial agents were isolated and identified by classical microbiology and mass spectrometry. Antibiotic resistance and adherence profiles were determined. Finally, resistance (mecA/SCCmec) and virulence (icaA and icaD) genes were detected in the Gram-positive population. The results showed that blepharitis was the most prevalent condition in the study population. A MALDI-TOF analysis revealed that Staphylococcus and Pseudomonas genus were the most prevalent as causal agents of infection. Resistances to ß-lactams were detected of 44 to 100%, followed by clindamycins, aminoglycosides, folate inhibitors, and nitrofurans. A multiple correspondence analysis showed a relationship between mecA genotype and ß-lactams resistance. The identification of SCCmecIII and SCCmecIV elements suggested community and hospital sources of infection. Finally, the coexistence of icaA+/icaD+/mecA(SCCmecIII) and icaA+/icaD+/mecA(SCCmecIV) genotypes was detected in S. aureus. The identification of resistant and virulent isolates highlights the importance of developing protocols that address the timely diagnosis of ocular infections. Herein, implications for the failure of antimicrobial therapy in the treatment of ocular infections in susceptible patients are analysed and discussed.

Typing of Candida spp. from Colonized COVID-19 Patients Reveal Virulent Genetic Backgrounds and Clonal Dispersion.

Advances in the knowledge of the pathogenesis of SARS-CoV-2 allowed the survival of COVID-19 patients in intensive care units. However, due to the clinical characteristics of severe patients, they resulted in the appearance of colonization events. Therefore, we speculate that strains of Candida spp. isolated from COVID-19 patients have virulent genetic and phenotypic backgrounds involved in clinical worsening of patients. The aim of this work was to virutype Candida spp. strains isolated from colonized COVID-19 patients, analyze their genomic diversity, and establish clonal dispersion in care areas. The virulent potential of Candida spp. strains isolated from colonized COVID-19 patients was determined through adhesion tests and the search for genes involved with adherence and invasion. Clonal association was done by analysis of intergenic spacer regions. Six species of Candida were involved as colonizing pathogens in COVID-19 patients. The genotype analysis revealed the presence of adherent and invasive backgrounds. The distribution of clones was identified in the COVID-19 care areas, where C. albicans was the predominant species. Evidence shows that Candida spp. have the necessary genetic tools to be able colonize the lungs, and could be a possible causal agent of coinfections in COVID-19 patients. The detection of dispersion of opportunistic pathogens can be unnoticed by classical epidemiology. Epidemiological surveillance against opportunistic fungal pathogens in COVID-19 patients is an immediate need, since the findings presented demonstrate the potential virulence of Candida spp.

Epidemiological Overview of Urogenital Gonorrhea in Mexico (2003-2020).

In Mexico, urogenital gonorrhea (UG) is one of the main sexually transmitted diseases notifiable by health systems around the world. Epidemiological data on sexually transmitted infections (STIs) in Mexico indicated that UG was "under control" until 2017. However, international epidemiological reports indicate the increase in incidence due to several factors, including an increase during the first year of the COVID-19 pandemic. These factors suggest that this phenomenon may occur in developing countries, including Mexico. Therefore, the aim of this study was to analyze national surveillance data on UG from 2003-2019 and the first year of the COVID-19 pandemic. An epidemiological study of cases and incidence of UG (2003-2020) was performed in the annual reports issued by the General Directorate Epidemiology in Mexico. Cases and incidence were classified and analyzed by year, sex, age group, and seasons (by temperature). Distribution of UG was carried out using heat maps for the whole country. Ultimately, a seasonal and correlation analysis was performed for UG cases versus temperature. The results showed that the distribution of cases and incidence by sex showed that there was no variation over 14 years. From 2016 onward, a significant increase in UG was observed before the pandemic. During the first year of the pandemic, a significant increase was observed in females aged 24-44 years. A heterogeneous distribution of UG was identified; however, border states were ranked among the top states with elevated incidences and cases. Lastly, the occurrence of UG was associated with temperature, related to summer. The information presented is intended to be useful to promote prevention and to contribute to visualize the distribution of UG over the last 18 years for decision making, and to show one of the consequences of the collapse of epidemiological surveillance of UG during the first year of the COVID-19 pandemic.

Effect of chronic administration of estradiol, progesterone, and tibolone on the expression and phosphorylation of glycogen synthase kinase-3ß and the microtubule-associated protein tau in the hippocampus and cerebellum of female rat.

Gonadal hormones regulate expression and activation of protein tau. Tibolone is a drug used as first- choice comprehensive treatment for the relief of menopausal symptoms, because it and its various metabolites have estrogenic properties and progestogenic/androgenic effects; however, the effect on the activation of tau protein and its signaling cascade in the brain is unknown. We studied the effect of chronic administration of estradiol (E2), progesterone (P4), and tibolone (TIB) on the expression and phosphorylation of microtubule-associated protein tau and glycogen synthase kinase-3ß (GSK3ß) in the hippocampus and cerebellum of ovariectomized rats. Ovariectomized adult female rats were implanted with pellets of vehicle, E2, or P4 or were treated with TIB by oral administration for 60 days. The animals were sacrificed, and tissue proteins were analyzed by Western blot. We observed that, in the hippocampus, administration of E2, P4, or TIB significantly decreased the protein content of hyperphosphorylated tau and increased the tau dephosphorylated form, whereas only treatment with TIB increased the content of the phosphorylated form of GSK3ß. In the cerebellum, E2 and TIB treatments resulted in a significant decrease in the expression of hyperphosphorylated tau, whereas E2 and TIB increased phosphorylated GSK3ß; P4 had no effect. These results indicate that chronic administration of gonadal hormones and tibolone modulates tau and GSK3ß phosphorylation in hippocampus and cerebellum of the rat and may exert a neuroprotective effect in these tissues.

Ultra-Processed Food Consumption during Pregnancy and Its Association with Maternal Oxidative Stress Markers.

Ultra-processed food (UPF) consumption during gestation may lead to increased oxidative stress (OS) and could affect pregnancy outcomes. This study aims to evaluate the association of UPF consumption during pregnancy with circulating levels of OS markers. Diet was assessed (average of three assessments) in 119 pregnant women enrolled in the OBESO perinatal cohort (Mexico), obtaining quantitative data and the percentage of energy that UPFs (NOVA) contributed to the total diet. Sociodemographic, clinical (pregestational body-mass index and gestational weight gain) and lifestyle data were collected. Maternal circulating levels of OS markers (malondialdehyde (MDA), protein carbonylation (PC), and total antioxidant capacity (TAC)) were determined at the third trimester of pregnancy. Adjusted linear regression models were performed to analyze the association between UPFs and OS markers. UPFs represented 27.99% of the total energy intake. Women with a lower UPF consumption (<75 percentile°) presented a higher intake of fiber, ω-3, ω-6, and a lower ω-6/3 ratio. Linear regression models showed that UPFs were inversely associated with TAC and MDA. Fiber intake was associated with PC. UPF intake during pregnancy may result in an increase in oxidative stress. When providing nutrition care, limiting or avoiding UPFs may be an intervention strategy that could promote a better antioxidant capacity in the body.

Massive sequencing of the V3-V4 hypervariable region of bronchoalveolar lavage from patients with COVID-19 and VAP reveals the collapse of the pulmonary microbiota.

Background. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is a predisposing factor for the development of healthcare-associated infections, of which ventilator-associated pneumonia (VAP) is one.Hypothesis. VAP is caused by ESKAPE bacteria and other pathogens not detected by microbiological culture.Aim. To elucidate the bacterial pathogens of severe coronavirus disease 2019 (COVID-19) and VAP patients by massive sequencing and to predict their degree of relationship with the age and sex of the patients.Methods. Analysis of ribosomal libraries of the V3-V4 hypervariable region obtained by Illumina sequencing of bronchoalveolar lavages from COVID-19 and VAP (first wave) patients from Hospital Juárez de México.Results. Acinetobacter and Pseudomonas were the main bacterial genera in the bronchoalveolar lavages (BALs) analysed. Other members of the ESKAPE group, such as Enterococcus and Klebsiella, were also identified. Taxonomic composition per patient showed that non-ESKAPE genera were present with significant relative abundances, such as Prevotella, Stenotrophomas, Enterococcus, Mycoplasma, Serratia and Corynebacterium. Kruskal-Wallis analysis proved that VAP acquisition is an adverse event that is not influenced by the sex and age of COVID-19 patients.Discussion. Metagenomic findings in COVID-19/VAP patients highlight the importance of implementing comprehensive microbiological diagnostics by including alternative tools for the detection of the causal agents of healthcare-associated infections (HAIs).Conclusions. Timely identification of bacteria 'not sought' in diagnostic bacteriology laboratories will allow specific and targeted treatments. Implications for the restricted diagnosis of VAP causative agents in COVID-19 patients and the presence of pathogens not detected by classical microbiology are analysed and discussed.

Serum miRNA profile as a potential tool for non-invasive gastric cancer diagnosis in Mexican patients.

INTRODUCTION: Gastric cancer (GC) is the third leading cause of cancer death and a major public health-care problem worldwide. At present, methods for plasma detection of cancer are limited. MicroRNAs (miRNAs) have recently been proposed as genetic regulators, which are deregulated in different types of cancer. The miRNAs are stable in serum/plasma and can be detected. Circulating miRNAs in plasma have been proposed as potential diagnostic biomarkers in GC. MATERIALS AND METHODS: After reviewing the relevant literature, the expression levels of seven miRNAs (miR-16, miR-21, miR-25, miR-26a, miR-92, miR-218, miR-223, and miR-451) were assessed by quantitative reverse transcription polymerase chain reaction using TaqMan microRNA Assays (Applied Biosystems) in plasma samples from GC patients (n = 80) and healthy controls (n = 80). RESULTS: Our results demonstrated that the expression levels of miR-21 and miR-25 were significantly upregulated in GC patients compared to healthy controls with a Fold Change of 11.551 and 60.129, respectively, while miR-223 showed downregulation in GC patients compared to healthy controls with a Fold Change of -247.281. The absolute value of Fold Change > 2 was consider significant, p < 0.05. CONCLUSIONS: Our results indicated that miR-21, miR-25, and miR-223 in plasma samples can be served as a potential noninvasive tool in detection of GC.

INTRODUCCIÓN: El cáncer gástrico (CG) es la tercera causa de muerte por cáncer y un importante problema de salud pública. Actualmente, los métodos para la detección de CG en plasma son limitados. Recientemente se han propuesto los microARNs (miARN) como reguladores genéticos en diferentes tipos de cáncer. Los miARN son estables en plasma, lo que permite una fácil detección, pudiendo usarse como biomarcadores en CG. MATERIALES Y MÉTODOS: Los niveles de expresión de siete miARN seleccionados (miR-16, miR-21, miR-25, miR-26a, miR-92, miR218, miR-223, miR-451) fueron evaluados mediante qRT-PCR mediante análisis con microARN TaqMan (Applied Biosystems) en muestras de plasma de pacientes con CG (n = 80) y controles sanos (n = 80). RESULTADOS: Se observo que los niveles de expresión de miR-21 y miR-25 estaban significativamente regulados al alza en los pacientes con CG en comparación con los controles con un Fold Change de 11.551 y 60.129 respectivamente, mientras que miR-223 mostró una regulación negativa con un cambio de -247,281. El valor absoluto de Fold Change >2 se consideró estadísticamente significativo, P <0,05. CONCLUSIONES: Nuestros resultados indicaron que miR 21, miR 25 y miR-223 en plasma pueden servir como una potencial herramienta no invasiva en la detección de CG.

Antisclerothic effect of tibolone by reducing proinflammatory cytokines expression, ROS production and LDL-ox uptake in THP-1 macrophages.

BACKGROUND: Cardiovascular disease is more frequent in menopausal women, which has been related to factor such as weight gain, altered fat distribution, and increased inflammation markers including adipokines (MCP-1, TNF-α, IL-6) and cytokines (IL-1, IL-6, TNF-α) produced by macrophages. In addition to their phagocytic activity, macrophages secrete cytokines and chemokines that induces cell recruitment, which is a process related to vascular damage that favors the formation of atheromatous plaques. Tibolone (Tb) therapy is used to reduce the symptoms of menopause as well as osteoporosis and it has been shown to decreases the risk of fractures. METHODS: To investigate the effect of tibolone in macrophage enzymatic activity, gene expression of cytokines, and its effect on foam cells formation. We use phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells. The cells were incubated 24 h and 48 h using pre and post-treatment schemes. We evaluated total ROS determination by NBT assay, expression of cytokines (IL-1ß, IL-6, TNF-α, NOS2, ARG1, TGFß) by RT-qPCR and foam cell formation in THP-1 differentiated macrophages stimulated with PMA. RESULTS: It was observed that the minor levels of total ROS determination were obtained with tibolone at 48 h in post-treatment scheme. Also, in a long term we found decrease the proinflammatory cytokines (IL-1ß, IL-6 and TNF-α). Finally, with treatment for 24 h with P4 y Tb we observed fewer LDL vesicles into macrophages cytoplasm. CONCLUSIONS: These results suggest that tibolone reduces the inflammatory process, also inhibits the foam cells formation; suggesting a possible role in reducing cardiovascular risk.

Nutrients, Mitochondrial Function, and Perinatal Health.

Mitochondria are active independent organelles that not only meet the cellular energy requirement but also regulate central cellular activities. Mitochondria can play a critical role in physiological adaptations during pregnancy. Differences in mitochondrial function have been found between healthy and complicated pregnancies. Pregnancy signifies increased nutritional requirements to support fetal growth and the metabolism of maternal and fetal tissues. Nutrient availability regulates mitochondrial metabolism, where excessive macronutrient supply could lead to oxidative stress and contribute to mitochondrial dysfunction, while micronutrients are essential elements for optimal mitochondrial processes, as cofactors in energy metabolism and/or as antioxidants. Inadequate macronutrient and micronutrient consumption can result in adverse pregnancy outcomes, possibly through mitochondrial dysfunction, by impairing energy supply, one-carbon metabolism, biosynthetic pathways, and the availability of metabolic co-factors which modulate the epigenetic processes capable of establishing significant short- and long-term effects on infant health. Here, we review the importance of macronutrients and micronutrients on mitochondrial function and its influence on maternal and infant health.

Efficacy of Diltiazem for the Control of Blood Pressure in Puerperal Patients with Severe Preeclampsia: A Randomized, Single-Blind, Controlled Trial.

BACKGROUND: Postpartum preeclampsia is a serious disease related to high blood pressure that occurs commonly within the first six days after delivery. OBJECTIVE: To evaluate if diltiazem improves blood pressure parameters in early puerperium patients with severe preeclampsia. Methodology. A randomized, single-blind longitudinal clinical trial of 42 puerperal patients with severe preeclampsia was carried out. Patients were randomized into two groups: the experimental group (n = 21) received diltiazem (60 mg) and the control group (n = 21) received nifedipine (10 mg). Both drugs were orally administered every 8 hours. Systolic, diastolic, and mean blood pressures as well as the heart rate were recorded and analyzed (two-way repeated measures ANOVA) at baseline and after 6, 12, 18, 24, 30, 36, 42, and 48 hours. Primary outcome measures were all the aforementioned blood pressure parameters. Secondary outcome measures included the number of hypertension and hypotension episodes along with the length of stay in the intensive care unit. RESULTS: No statistical differences were found between groups (diltiazem vs. nifedipine) regarding basal blood pressure parameters. Interarm differences in blood pressure (systolic, diastolic, and mean) and heart rate were statistically significant between treatment groups from 6 to 48 hours. Patients in the diltiazem group had lower blood pressure levels than patients in the nifedipine group. Significantly, patients who received diltiazem had fewer hypertension and hypotension episodes and stayed fewer days in the intensive care unit than those treated with nifedipine. CONCLUSIONS: Diltiazem controlled arterial hypertension in a more effective and uniform manner in patients under study than nifedipine. Patients treated with diltiazem had fewer collateral effects and spent less time in the hospital. This trial is registered with NCT04222855.

Effects of (-)-epicatechin on neuroinflammation and hyperphosphorylation of tau in the hippocampus of aged mice.

Evidence has implicated oxidative stress (OS) and inflammation as drivers of neurodegenerative pathologies. We previously reported on the beneficial effects of (-)-epicatechin (Epi) treatment on aging-induced OS and its capacity to restore modulators of mitochondrial biogenesis in the prefrontal cortex of 26-month-old male mice. In the present study using the same mouse model of aging, we examined the capacity of Epi to mitigate hippocampus OS, inflammation, hyperphosphorylation of tau protein, soluble ß-amyloid protein levels, cell survival, memory, anxiety-like behavior levels and systemic inflammation. Mice were subjected to 4 weeks of Epi treatment (1 mg kg-1 day-1) and samples of the hippocampus were obtained. Assessments of the OS markers, protein carbonyls, and malondialdehyde levels demonstrated their significant increase (∼3 fold) with aging that were partially suppressed by Epi. The protein levels of the glial fibrillary acidic protein, inflammatory factor 1 (Iba1), pro-inflammatory cytokines, interleukins (IL-1ß, IL-3, 5, 6 and 15), cyclooxygenase 2, tumor necrosis factor α, nuclear factor-activated B cells and interferon γ increase with aging and were also significantly decreased with Epi treatment. However, anti-inflammatory cytokines, IL-1ra, IL-10 and 11 decrease with aging and were restored with Epi. Epi also reversed the aging effects on the hyperphosphorylation of tau, increased soluble ß-amyloid levels (∼2 fold), cellular death (as per caspase 3 and 9 activity), and reduced nerve growth factor and triggering receptor expressed on myeloid cells 2 levels. Measures of anxiety like-behavior and memory demonstrated improvements with Epi treatment. Indicators of systemic inflammation increase with aging and Epi was capable of decreasing blood inflammatory markers. Altogether, the results show a significant capacity of Epi to mitigate hippocampus OS and inflammation leading to improved brain function.

Analysis of Antioxidant Consumption, Body Mass Index and the Waist-Hip Ratio in Early Postmenopause.

Oxidative stress is present in early postmenopause. Antioxidants, present in food, avoid or limit the damage caused by free radicals. The aim of this study was to analyze whether the consumption of vitamin A, vitamin C, and Selenium was adequate in postmenopausal women and its relationship with levels of malondialdehyde. A descriptive, cross-sectional prospective clinical study was carried out with 132 women (45⁻55 years old) in postmenopause. The body mass index (BMI) and the waist-to-hip ratio (WHR) were calculated. The participants were surveyed about their food consumption for seven days. The plasmatic concentration of malondialdehyde was quantified by the methyl-phenyl-indole method. The women were grouped according to their BMI. All groups showed similar consumption of proteins, lipids, and carbohydrates, which exceeded the daily recommended level. According to the WHR, 87% had android fat distribution. Selenium, vitamin C, and vitamin A intake were below the daily recommended/suggested levels. The greater the BMI, the higher the plasmatic concentration of malondialdehyde in the patients. It was observed an elevated caloric intake, android fat distribution, and a greater BMI was accompanied by a lower consumption of antioxidants and an increased level of malondialdehyde.

[Effect of the management of class I obesity with metformin on metalloproteinase activity in patients with chronic periodontitis]. / Efecto del manejo de la obesidad clase I con metformina sobre actividad de metaloproteinasas en pacientes con periodontitis crónica.

INTRODUCTION: Introduction: in Mexico the main problem in public health is obesity and other diseases that are associated whit this condition, including oral health. Objective: to evaluate the effect of metformin treatment in patients with class I obese on the activity of metalloproteinases present in periodontium with chronic periodontitis. Methods: a clinical study was conducted in 68 patients with class I obesity and periodontal disease. They were divided into 4 groups. 2 of them, in addition to the periodontal treatment, were administered metformin 850 mg per day for six weeks; 2 samples were taken per patient of periodontal tissue before and after each treatment, body mass index, plaque index and inflammation were measured. Acrylamide gel zymography was used to measure the activity of metalloproteinases in the sample of tissue collected. The data obtained were analyzed by descriptive statistics, student t for related samples and one-way ANOVA was performed considering p < 0.01 as statistically significant. Results: in the group of patients who were administered metformin at the end of the treatment, there was a decrease in the body mass index, the degree of inflammation and lower metalloproteinase activity, compared with the control group (65% vs 25%; < 0.01). Conclusions: treatment with metformin in patients with obesity class I and periodontal disease decreases BMI, improves the symptoms of chronic periodontitis and decreases the activity of metalloproteinases 1, 3, 8, V present in periodontium of these patients.

INTRODUCCIÓN: Introducción: el principal problema de salud pública en México es la obesidad y sus enfermedades asociadas, incluyendo las bucales. Objetivo: evaluar el efecto del tratamiento con metformina en pacientes obesos de clase I sobre la actividad de las metaloproteinasas presentes en el periodonto con periodontitis crónica. Métodos: se realizó un estudio clínico con 68 pacientes mujeres con obesidad de clase I y enfermedad periodontal. Se dividieron en 4 grupos; a 2 de ellos, además del tratamiento periodontal, se les administro metformina de 850 mg al día durante seis semanas. Se tomaron 2 muestras por paciente de tejido periodontal antes y después de cada tratamiento y se midió el índice de masa corporal (IMC), el índice de placa dentobacteriana y de inflamación. Mediante zimografía en gel de acrilamida se midió la actividad de las metaloproteinasas en la muestra de tejido recolectada. Los datos obtenidos fueron analizados mediante estadística descriptiva t de student para muestras relacionadas y se realizó ANOVA de una vía considerando p < 0,01 como estadísticamente significativa. Resultados: en el grupo de pacientes a las que se les administro metformina al final del tratamiento se observó una disminución del índice de masa corporal, del grado de inflamación y menor actividad de metaloproteinasas respecto al grupo control (65% frente a 25%; p < 0,01). Conclusiones: el tratamiento con metformina en pacientes con obesidad de clase I y enfermedad periodontal disminuye el IMC, mejora los síntomas de la periodontitis crónica y disminuye la actividad de las metaloproteinasas 1, 3, 8 y V presentes en el periodonto de estos pacientes.