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1.
Artículo en Inglés | MEDLINE | ID: mdl-38797277

RESUMEN

STUDY OBJECTIVE: To assess the effect of preoperative bilateral ultrasound-guided quadratus lumborum nerve block (QLB) on quality of recovery after minimally invasive hysterectomy, in an enhanced recovery after surgery setting. DESIGN: Randomized, controlled, double-blinded trial (Canadian Task Force level I). SETTING: University-affiliated tertiary medical center. PATIENTS: All women undergoing an elective robotic or laparoscopic hysterectomy. Women with chronic pain, chronic anticoagulation, and body mass index >50 kg/m2 were excluded. INTERVENTION: Patients were randomized with a 1:1 allocation, to one of the following 2 arms, and stratified based on robotic versus laparoscopic approach. 1. QLB: QLB (bupivacaine) + sham local trocar sites infiltration (normal saline) 2. Local infiltration: sham QLB (normal saline) + local infiltration (bupivacaine) MEASUREMENTS AND MAIN RESULTS: The primary outcome was defined as the quality of recovery score based on the validated questionnaire Quality of Recovery, completed 24 hours postoperatively. Secondary outcomes included dynamic pain scores, accumulated opioid consumption up to 24 hours, postoperative nausea and vomiting, surgical complications, length of hospital stay, time to first pain medication administration in the postanesthesia care unit, and adverse events. A total of 76 women were included in the study. Demographic characteristics were similar in both groups. Median age was 44 years (interquartile range 39-50), 47% of the participants were African American, and mean body mass index was 32.8 kg/m2 (standard deviation [SD] 8.1). The mean Quality of Recovery score was 179.1 (SD ± 10.3) in the QLB and 175.6 (SD ± 9.7) for the local anesthesia group (p = .072). All secondary outcomes were comparable between groups. CONCLUSIONS: QLBs do not significantly improve quality of recovery after elective robotic or laparoscopic hysterectomy compared with local anesthetic port site infiltration.

2.
Am J Obstet Gynecol ; 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38761838

RESUMEN

BACKGROUND: Single-use materials and equipment are regularly opened by the surgical team during procedures but left unused, potentially resulting in superfluous costs and excess environmental waste. OBJECTIVE: This study aimed to estimate the excess use of surgical supplies in minimally invasive benign gynecologic surgeries. STUDY DESIGN: This is a prospective observational study conducted at a university-affiliated single tertiary medical center. Designated study personnel were assigned to observe surgical procedures performed during July to September 2022. Surgical teams were observed while performing surgeries for benign indications. The teams were not informed of the purpose of the observation to avoid potential bias. Disposable materials and equipment opened during the procedure were documented. Excess supplies were defined as those opened but left unused before being discarded. Costs per item of the excess supplies were estimated on the basis of material and equipment costs provided by the hospital. RESULTS: A total of 99 surgeries were observed, including laparoscopic (32%), robotic (39%), hysteroscopic (14%), vaginal (11%), and laparotomy procedures (3%). Excess use of surgical supplies was documented in all but one procedure. The total cost across all surgeries reached $6357. The contained tissue extraction bag was the most expensive item not used (Applied Medical, Rancho Santa Margarita, CA; $390 per unit) in 4 procedures, contributing 25.54% to the total cost. Raytec was the most common surgical waste, with a total of n=583 opened but unused (average n=5.95 per surgery). A significant difference was found in the rate of excess supplies across the surgical approaches, with robotic surgery contributing 52.19% of the total cost (P=.01). CONCLUSION: Excess use of disposable materials and equipment is common in minimally invasive benign gynecologic surgeries and contributes to superfluous costs and excess environmental waste. It is predominantly attributed to the opening of inexpensive materials that are left unused during the procedure. Increased awareness of costs and generated waste may reduce excess use of surgical supplies and should be further explored in future research.

3.
AJP Rep ; 14(1): e74-e79, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38370330

RESUMEN

Uterine leiomyomas are common benign smooth muscle tumors that often occur during the reproductive years. Although many cases may not result in significant complications, negative pregnancy outcomes have been associated with the size and location of the fibroids. Degeneration of fibroids can occur as early as the late first trimester when they undergo significant volumetric growth, contributing to pain during pregnancy. While myomectomy is typically avoided during pregnancy, conservative management with anti-inflammatory medications may be effective. Surgical removal or preterm delivery may be necessary if symptoms persist. Abdominal compartment syndrome (ACS) is a rare condition characterized by sustained elevated intra-abdominal pressure leading to organ failure. Although ACS resulting from large-volume leiomyomas in the postpartum period has not been previously described, we present a case of a 25-year-old patient with massive uterine fibroids who required indicated preterm delivery via primary cesarean section at 25 weeks gestation. Her postpartum course was complicated by ACS, requiring emergent surgical decompression. When a large fibroid burden is present during pregnancy or in the postpartum period, ACS should be considered in the differential diagnosis. Early diagnosis and timely surgical decompression are necessary to prevent organ dysfunction and worsening maternal outcomes.

4.
Case Rep Oncol ; 16(1): 1274-1279, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37928866

RESUMEN

A 38-year-old female with an etonogestrel implant in place and history of previous ectopic pregnancy presented with acute abdominal pain and vaginal bleeding. She was found to have a beta-hCG of >12,000 mIU/mL and free fluid noted on a focused assessment with sonography in trauma exam. She underwent an emergent diagnostic laparoscopy due to the suspicion of a ruptured ectopic pregnancy. Findings at the time of surgery included a normal-appearing uterus and left fallopian tube, a surgically absent right fallopian tube and large volume hemoperitoneum with a rapidly expanding left retroperitoneal hematoma. A postoperative computerized tomography (CT) angiogram suggested active bleeding from a pseudoaneurysm of the left renal artery which was successfully embolized by interventional radiology. Biopsy confirmed gestational trophoblastic neoplasia (GTN) after metastases to the brain. In this report, we describe the details of this case of GTN with an atypical presentation.

5.
J Minim Invasive Gynecol ; 30(11): 884-889, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37422052

RESUMEN

STUDY OBJECTIVE: To investigate the incidence of venous thromboembolism (VTE) in patients undergoing large specimen hysterectomy for benign indications. To evaluate the impact of route of surgery and operative time in the development of VTE in this population. DESIGN: Retrospective cohort study (Canadian Task Force Classification II2) of targeted hysterectomy data prospectively collected from the American College of Surgeons National Surgical Quality Improvement Program involving over 500 hospitals across the United States. SETTING: National Surgical Quality Improvement Program Database. PATIENTS: Women aged 18 years or older undergoing hysterectomy for benign indications between 2014 and 2019. Patients were further classified into 4 groups according to uterine weight: <100 g, 100-249 g, 250 g-499 g, and specimens ≥500 g. INTERVENTIONS: Current Procedural Terminology codes were used to identify cases. Variables including age, ethnicity, body mass index, smoking status, diabetes, hypertension, blood transfusion, and American Society of Anesthesiologists classification system scores were collected. Cases were stratified by route of surgery, operative time, and uterine weight. MEASUREMENTS AND MAIN RESULTS: A total of 122,418 hysterectomies occurring between 2014 and 2019 were included in our study, of which 28,407 (23.2%) patients underwent abdominal, 75,490 (61.7%) laparoscopic, and 18,521 (15.1%) vaginal hysterectomy. The overall rate of VTE in patients with large specimen hysterectomies (≥500 g) was 0.64%. After multivariable adjustment, there was no significant difference in the odds of VTE between uterine weight groups. Only 30% of the surgeries with uterine weight above 500 g were performed with minimally invasive surgical routes. Patients who underwent minimally invasive hysterectomy had lower odds of VTE via laparoscopic (adjusted odds ratio [aOR] 0.62; confidence interval [CI]: 0.48-0.81) and vaginal (aOR 0.46; CI: 0.31-0.69) routes compared to laparotomy. Prolonged operative time (>120 min) was associated with increased odds of VTE (aOR 1.86; CI:1.51-2.29). CONCLUSION: The occurrence of VTE after a benign large specimen hysterectomy is rare. The odds of VTE is higher with longer operative times and lower with minimally invasive approaches, even for markedly enlarged uteri.


Asunto(s)
Tromboembolia Venosa , Humanos , Femenino , Estados Unidos , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Histerectomía/efectos adversos , Histerectomía Vaginal/efectos adversos
6.
Artículo en Inglés | MEDLINE | ID: mdl-37140589

RESUMEN

BACKGROUND: The aim of this study was to evaluate rate of complications with the use of prophylactic ureteral localization stents (PULSe) in gynecologic surgery. To compare the occurrence of complications according to the indication of surgery. METHODS: This retrospective study included 1248 women who underwent 1275 different gynecologic surgeries with PULSe between 2007 and 2020. Data was collected regarding patient characteristics (age, sex, race, ethnicity, parity, previous pelvic surgery, creatinine), operative characteristics (trainee, guidewire use, indication) and complications in the first 30 days (ureteral injury, urinary tract complication, re-stenting, hydronephrosis, urinary tract infection (UTI), pyelonephritis, emergency room visit, re-admission). RESULTS: Median age was 57 years (range: 18-96 years), most women were Caucasian (88.9%), and had previous pelvic surgery (77.7%). Indication of surgery was benign for 459 (36.0%), female pelvic medicine and reconstructive surgery (FPMRS) for 545 (42.7%), and gynecologic oncology (gyn-onc) for 271 (21.3%). Disabling complications occurred rarely with 8 patients (0.6%) having a ≥III Clavien Dindo Grade (CDG), and only 1 (0.08%) ≥IV CDG. Statistically significant differences between benign, FPMRS, and gyn-onc groups were noted for re-stenting (0.9% vs. 0.0% vs. 1.1%, P=0.020), hydronephrosis (0.9% vs. 0.2% vs. 2.2%, P=0.014), UTI (4.6% vs. 9.4% vs. 7.0%, P=0.016), and re-admission (2.4% vs. 1.1% vs. 4.4%, P=0.014). CONCLUSIONS: The incidence of 30-day CDG III and IV complications after PULSe placement is low. FPMRS patients had a higher rate of complicated UTI, however gyn- onc patients appear to be at overall higher risk of stent related complications when compared to surgeries for FPMRS or benign indications.

7.
bioRxiv ; 2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36865100

RESUMEN

Interferons are essential for innate and adaptive immune responses against a wide variety of pathogens. Interferon lambda (IFN-λ) protects mucosal barriers during pathogen exposure. The intestinal epithelium is the first contact site for Toxoplasma gondii (T. gondii) with its hosts and the first defense line that limits parasite infection. Knowledge of very early T. gondii infection events in the gut tissue is limited and a possible contribution of IFN-λ has not been investigated so far. Here, we demonstrate with systemic interferon lambda receptor (IFNLR1) and conditional (Villin-Cre) knockout mouse models and bone marrow chimeras of oral T. gondii infection and mouse intestinal organoids a significant impact of IFN-λ signaling in intestinal epithelial cells and neutrophils to T. gondii control in the gastrointestinal tract. Our results expand the repertoire of interferons that contribute to the control of T. gondii and may lead to novel therapeutic approaches against this world-wide zoonotic pathogen.

8.
PLoS Pathog ; 19(1): e1011003, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36603017

RESUMEN

Toxoplasma gondii (T. gondii) is a zoonotic apicomplexan parasite that is an important cause of clinical disability in humans. On a global scale, one third of the human population is infected with T. gondii. Mice and other small rodents are believed to be responsible for transmission of T. gondii to the domestic cat, its definitive host. Interferon-inducible Immunity-Related GTPases (IRG proteins) are important for control of murine T. gondii infections. Virulence differences between T. gondii strains are linked to polymorphic rhoptry proteins (ROPs) that cooperate to inactivate individual IRG family members. In particular, the pseudokinase ROP5 isoform B is critically important in laboratory strains of mice. We identified T. gondii ROP39 in complex with ROP5B and demonstrate its contribution to acute T. gondii virulence. ROP39 directly targets Irgb10 and inhibits homodimer formation of the GTPase leading to an overall reduction of IRG protein loading onto the parasitophorous vacuolar membrane (PVM). Maintenance of PVM integrity rescues the parasite from IRG protein-mediated clearance in vitro and in vivo. This study identifies a novel T. gondii effector that is important for specific inactivation of the IRG resistance system. Our data reveal that yet unknown T. gondii effectors can emerge from identification of direct interaction partners of ROP5B.


Asunto(s)
Parásitos , Toxoplasma , Toxoplasmosis , Animales , Ratones , Humanos , Gatos , Toxoplasma/metabolismo , Parásitos/metabolismo , Virulencia , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , GTP Fosfohidrolasas/metabolismo
10.
Nat Commun ; 13(1): 1168, 2022 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-35246532

RESUMEN

The apicomplexan parasite Toxoplasma gondii forms bradyzoite-containing tissue cysts that cause chronic and drug-tolerant infections. However, current in vitro models do not allow long-term culture of these cysts to maturity. Here, we developed a human myotube-based in vitro culture model of functionally mature tissue cysts that are orally infectious to mice and tolerate exposure to a range of antibiotics and temperature stresses. Metabolomic characterization of purified cysts reveals global changes that comprise increased levels of amino acids and decreased abundance of nucleobase- and tricarboxylic acid cycle-associated metabolites. In contrast to fast replicating tachyzoite forms of T. gondii these tissue cysts tolerate exposure to the aconitase inhibitor sodium fluoroacetate. Direct access to persistent stages of T. gondii under defined cell culture conditions will be essential for the dissection of functionally important host-parasite interactions and drug evasion mechanisms. It will also facilitate the identification of new strategies for therapeutic intervention.


Asunto(s)
Fibras Musculares Esqueléticas , Toxoplasma , Animales , Interacciones Huésped-Parásitos , Humanos , Metaboloma , Ratones , Fibras Musculares Esqueléticas/parasitología , Toxoplasma/metabolismo
11.
J Robot Surg ; 16(6): 1273-1280, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35025036

RESUMEN

The advantages of dual console use in robotic surgical education have not been described. The aims of this study are to compare fellow console time, surgical steps performed, and surgical takeovers between attending and fellow surgeons using dual versus single console robotic systems. Participants included minimally invasive gynecologic surgery (MIGS) fellows (N = 3) and subspecialty trained gynecologic surgeons (N = 5). Prospective data were obtained on 126 patients (N = 77 single console, N = 49 dual console) undergoing robotic hysterectomy. Variables included demographics, surgical characteristics (fellow, month of fellowship, attending surgeon, concomitant oophorectomy, additional surgical procedures, estimated blood loss, specimen weight), and outcomes (console time, docking time, console time/docking time ratio, total case time, number of surgical steps performed by the fellow, number of surgical takeovers, complications). After controlling for potential confounders, fellows spent a mean of 25.8 min longer (P < 0.001) at the console in dual console operations compared to single. Dual console surgeries had a greater number of steps performed by the fellow (OR[> 5 steps]: 3.37, P = 0.009), a higher console time/docking time ratio (P < 0.001), and more surgical takeovers between fellow and attending (OR [> 1 takeover]: 3.53, P < 0.001). There were no significant differences between the two groups regarding docking time (P = 0.15), case time (P = 0.79), or complications (P = 0.30). Our findings suggest dual console robotic training provide fellows the opportunity for more "hands-on" experience with longer console time, higher number of surgical steps performed, and added interaction with the attending surgeon when compared with single console training. These surgical metrics provide objectivity in competency-based robotic training without increasing the complications or surgical time.


Asunto(s)
Ginecología , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Femenino , Procedimientos Quirúrgicos Robotizados/métodos , Estudios Prospectivos , Robótica/educación , Becas
13.
J Minim Invasive Gynecol ; 28(11): 1927-1934, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34010696

RESUMEN

STUDY OBJECTIVE: The "illusion of validity" is a cognitive bias in which the ability to interpret and predict surgical performance accurately is overestimated. To address this bias, we assessed participants comparing fundamentals of laparoscopic surgery (FLS) and non-FLS tasks with cadaveric vaginal cuff suturing to determine the most representative simulation task for laparoscopic vaginal cuff suturing. DESIGN: Validity (Messick framework) study comparing FLS and non-FLS tasks with cadaveric vaginal cuff suturing. SETTING: Simulation center cadaver laboratory. PARTICIPANTS: Obstetrics and gynecology residents (n = 21), minimally invasive gynecologic surgery fellows (n = 3), gynecologic surgical subspecialists (n = 4), general obstetrician/gynecologists (n = 10). INTERVENTIONS: Tasks included a simulated vaginal cuff (ipsilateral port placement), needle passage through a metal eyelet loop (contralateral and ipsilateral), and intracorporeal knot tying (contralateral and ipsilateral). Simulation task times were compared with the placement of the first cadaveric vaginal cuff suture time, as well as the in-person and blinded Global Operative Assessment of Laparoscopic Skills (GOALS) score ("relations to other variables" validity evidence). Statistical analyses included Spearman's test of correlation (continuous and ordinal variables) or Wilcoxon rank sum test (categoric variables). MEASUREMENTS AND MAIN RESULTS: There was a stronger association with cadaver cuff suturing time for simulated vaginal cuff suturing time (r = 0.73, p <.001) compared with FLS intracorporeal contralateral suturing time (r = 0.54, p <.001). Additional measures associated with cadaveric performance included subspecialty training (median: 82 vs 185 seconds, p = .002), number of total laparoscopic hysterectomies (r = -0.53, p <.001), number of laparoscopic cuff closures (r = -0.61, p <.001), number of simulated laparoscopic suturing experiences (r = -0.51, p <.001), and eyelet contralateral time (r = 0.52, p <.001). Strong agreement between the in-person and blinded GOALS (intraclass correlation coefficient = 0.80) supports response process evidence. Correlations of cadaver cuff time with in-person (Spearman's r = -0.84, p <.001) and blinded GOALS (r = -0.76, p <.001) supports relations to other variables evidence CONCLUSION: The weaker correlation between FLS suturing and cadaver cuff suturing compared with a simulated vaginal cuff model may lead to an "illusion of validity" for assessment in gynecology. Since gynecology specific validity evidence has not been well established for FLS, we recommend prioritizing the use of a simulated vaginal cuff suturing assessment in addition to FLS.


Asunto(s)
Ilusiones , Laparoscopía , Competencia Clínica , Femenino , Humanos , Técnicas de Sutura , Suturas
14.
Microb Pathog ; 148: 104465, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32860878

RESUMEN

In human ocular toxoplasmosis, serotype is related with greater severity. We analyzed Toxoplasma GRA6 serotype in 23 patients with ocular toxoplasmosis (13 confirmed, two co-infections- and eight unconfirmed cases) and 20 individuals chronically infected with Toxoplasma but without ocular involvement. In patients with ocular toxoplasmosis, we also studied host gene polymorphisms related to immune response (IL-1ß; IL-1α; IL-10; IFN-γ; TNF-α, IL-12), IL-17R, TLR-9, and P2RX7. Additionally, eight patients were studied for the production of TNFα, IL1-ß, IFN-γ and IL-10 by their peripheral leukocytes after ex vivo stimulation with soluble Toxoplasma antigens. There were no differences in the distribution of serotypes (GRA6-I versus GRA6 non-I) between infected individuals with- or without ocular involvement. Seropositivity for GRA6-I was associated with higher number of retinal lesions and higher levels of IL-1ß. Two polymorphisms were associated with specific clinical manifestations of ocular toxoplasmosis: IL-10 -819 C/T with bilateral lesions and IL-12 + 169,774 A/C with synechia. Higher levels of IL-10 were found in patients with the allele G/G at the polymorphic region IL-10 -1082. People with a GRA6 I serotype and possessing the allele G/G at the polymorphic region TNFα-857 suffered from an increased number of retinal lesions. We found a positive association between host cytokine genes polymorphisms and GRA6 serotypes correlated with specific clinical manifestations and immune response in ocular toxoplasmosis.


Asunto(s)
Toxoplasma , Toxoplasmosis Ocular , Citocinas/genética , Humanos , Interleucina-12 , Polimorfismo Genético , Serotipificación , Toxoplasma/genética , Toxoplasmosis Ocular/genética
15.
Minerva Ginecol ; 72(5): 310-315, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32403916

RESUMEN

BACKGROUND: Office hysteroscopy (OH) is becoming increasingly popular. Our objective was to determine the use patterns, reported pain scores, and success rates of OH with the 2.9 mm Storz TrophyScope® and handheld portable Cooper surgical Endosee® device in a clinic without previous office hysteroscopy experience. METHODS: A prospective cohort study of a hysteroscopy quality improvement database was conducted in a tertiary care center gynecology clinic. Patients undergoing OH with either the Storz TrophyScope® or Cooper Surgical Endosee® device were included. RESULTS: Of the 171 office hysteroscopies, 77 utilized the TrophyScope®, with 8 (10%) being inadequate, while 94 utilized Endosee®, with 13 (14%) being inadequate (P=0.50). Of the 13 inadequate Endosee® hysteroscopies, 4 (31%) were due to visualization, 4 (31%) to patient intolerance, 3 (23%) to cervical stenosis, and 2 (15%) to a combination of these factors. Of the 8 inadequate TrophyScope® hysteroscopies, 7 (87%) were due to patient intolerance and 1 (13%) to cervical stenosis. Of the 150 adequate office procedures performed, 52 cases underwent subsequent procedures in the operating room (OR). Of these, 26 (84%) of 31 Endosee® cases and 18 (86%) of 21 TrophyScope® cases were in agreement with OR procedure findings. A subgroup analysis comparing mean pain levels did not significantly differ between the two hysteroscopes. CONCLUSIONS: There was no difference in accuracy with OR pathologic diagnoses, adequacy of procedure, and reported pain scores when comparing the TrophyScope® and Endosee® in this prospective cohort. Larger studies are needed to confirm the sensitivity, and specificity for these newer, disposable office hysteroscopic devices.


Asunto(s)
Histeroscopios , Histeroscopía , Procedimientos Quirúrgicos Ambulatorios , Femenino , Humanos , Dolor , Embarazo , Estudios Prospectivos
16.
Artículo en Inglés | MEDLINE | ID: mdl-31867288

RESUMEN

Toxoplasma gondii ROP16 and ROP18 proteins have been identified as important virulence factors for this parasite. Here, we describe the effect of ROP16 and ROP18 proteins on peripheral blood mononuclear cells (PBMCs) from individuals with different clinical status of infection. We evaluated IFN-γ, IL-10, and IL-1ß levels in supernatants from PBMCs cultures infected with tachyzoites of the T. gondii wild-type RH strain or with knock-out mutants of the rop16 and rop18 encoding genes (RHΔrop16 and RHΔrop18). Cytokine secretion was compared between PBMCs obtained from seronegative individuals (n = 10), with those with chronic asymptomatic (n = 8), or ocular infection (n = 12). We also evaluated if polymorphisms in the genes encoding for IFN-γ, IL-10, IL-1ß, Toll-like receptor 9 (TLR9), and purinoreceptor P2RX7 influenced the production of the encoded proteins after ex vivo stimulation. In individuals with chronic asymptomatic infection, only a moderate effect on IL-10 levels was observed when PBMCs were infected with RHΔrop16, whereas a significant difference in the levels of inflammatory cytokines IFN-γ and IL-1ß was observed in seronegative individuals, but this was also dependent on the host's cytokine gene polymorphisms. Infection with ROP16-deficient parasites had a significant effect on IFN-γ production in previously non-infected individuals, suggesting that ROP16 which is considered as a virulence factor plays a role during the primary infection in humans, but not in the secondary immune response.


Asunto(s)
Leucocitos Mononucleares/inmunología , Proteínas Serina-Treonina Quinasas/inmunología , Proteínas Tirosina Quinasas/inmunología , Proteínas Protozoarias/inmunología , Toxoplasma/inmunología , Toxoplasmosis/inmunología , Toxoplasmosis/parasitología , Citocinas/metabolismo , Fibroblastos , Interacciones Huésped-Parásitos/genética , Interacciones Huésped-Parásitos/inmunología , Humanos , Leucocitos Mononucleares/metabolismo , Polimorfismo Genético , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT6/metabolismo , Toxoplasma/patogenicidad , Toxoplasmosis/genética , Virulencia , Factores de Virulencia/inmunología
17.
Nat Commun ; 10(1): 1645, 2019 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-30948711

RESUMEN

The original version of this Article contained an error in the Acknowledgements, which incorrectly omitted the following: 'C.C., C.A., and J.C.H. were supported by the Fundação Calouste Gulbenkian through a grant from the Instituto Gulbenkian de Ciência and by the research infrastructure Congento, project LISBOA-01-0145-FEDER-022170, co-financed by Lisboa Regional Operational Programme (Lisboa 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and Foundation for Science and Technology (Portugal).' This has been corrected in both the PDF and HTML versions of the Article.

18.
Nat Commun ; 10(1): 1233, 2019 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-30874554

RESUMEN

Some strains of the protozoan parasite Toxoplasma gondii (such as RH) are virulent in laboratory mice because they are not restricted by the Immunity-Related GTPase (IRG) resistance system in these mouse strains. In some wild-derived Eurasian mice (such as CIM) on the other hand, polymorphic IRG proteins inhibit the replication of such virulent T. gondii strains. Here we show that this resistance is due to direct binding of the IRG protein Irgb2-b1CIM to the T. gondii virulence effector ROP5 isoform B. The Irgb2-b1 interface of this interaction is highly polymorphic and under positive selection. South American T. gondii strains are virulent even in wild-derived Eurasian mice. We were able to demonstrate that this difference in virulence is due to polymorphic ROP5 isoforms that are not targeted by Irgb2-b1CIM, indicating co-adaptation of host cell resistance GTPases and T. gondii virulence effectors.


Asunto(s)
GTP Fosfohidrolasas/inmunología , Interacciones Huésped-Parásitos/inmunología , Proteínas Protozoarias/inmunología , Toxoplasma/patogenicidad , Toxoplasmosis Animal/inmunología , Animales , Resistencia a la Enfermedad/genética , Resistencia a la Enfermedad/inmunología , Femenino , Fibroblastos , GTP Fosfohidrolasas/genética , GTP Fosfohidrolasas/metabolismo , Células HEK293 , Interacciones Huésped-Parásitos/genética , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Isoformas de Proteínas , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Selección Genética/inmunología , Toxoplasma/inmunología , Toxoplasmosis Animal/parasitología , Virulencia/inmunología
19.
Pharm Biol ; 55(1): 96-100, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27927103

RESUMEN

CONTEXT: Agastache mexicana ssp. mexicana (Kunth) Lint & Epling (Lamiaceae), popularly known as 'toronjil morado', is used in Mexican traditional medicine for the treatment of several diseases such as hypertension, anxiety and respiratory disorders. OBJECTIVE: This study investigates the relaxant action mechanism of A. mexicana ssp. mexicana essential oil (AMEO) in guinea-pig isolated trachea model. MATERIALS AND METHOD: AMEO was analyzed by GC/MS. The relaxant effect of AMEO (5-50 µg/mL) was tested in guinea-pig trachea pre-contracted with carbachol (3 × 10 - 6 M) or histamine (3 × 10 - 5 M) in the presence or absence of glibenclamide (10 - 5 M), propranolol (3 × 10 - 6 M) or 2',5'-dideoxyadenosine (10 - 5 M). The antagonist effect of AMEO (10-300 µg/mL) against contractions elicited by carbachol (10 - 15-10 - 3 M), histamine (10 - 15-10 - 3 M) or calcium (10-300 µg/mL) was evaluated. RESULTS: Essential oil composition was estragole, d-limonene and linalyl anthranilate. AMEO relaxed the carbachol (EC50 = 18.25 ± 1.03 µg/mL) and histamine (EC50 = 13.3 ± 1.02 µg/mL)-induced contractions. The relaxant effect of AMEO was not modified by the presence of propranolol, glibenclamide or 2',5'-dideoxyadenosine, suggesting that effect of AMEO is not related to ß2-adrenergic receptors, ATP-sensitive potassium channels or adenylate cyclase activation. AMEO was more potent to antagonize histamine (pA2' = -1.507 ± 0.122) than carbachol (pA2' = -2.180 ± 0.357). Also, AMEO antagonized the calcium chloride-induced contractions. CONCLUSION: The results suggest that relaxant effect of AMEO might be due to blockade of calcium influx in guinea-pig trachea smooth muscle. It is possible that estragole and d-limonene could contribute majority in the relaxant effect of AMEO.


Asunto(s)
Agastache/química , Broncoconstricción/efectos de los fármacos , Broncodilatadores/farmacología , Relajación Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Aceites Volátiles/farmacología , Extractos Vegetales/farmacología , Tráquea/efectos de los fármacos , Animales , Broncodilatadores/aislamiento & purificación , Señalización del Calcio/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Cromatografía de Gases y Espectrometría de Masas , Cobayas , Técnicas In Vitro , Masculino , Músculo Liso/metabolismo , Aceites Volátiles/aislamiento & purificación , Fitoterapia , Componentes Aéreos de las Plantas , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Tráquea/metabolismo
20.
Am J Perinatol ; 34(4): 403-408, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27606778

RESUMEN

Objective The American Congress of Obstetricians and Gynecologists (ACOG) task force on hypertension in pregnancy introduced a new definition of superimposed preeclampsia (SIP) adding severe features (SF) as new criteria to define severe disease. They also recommended that those with SIP be delivered ≥ 37 weeks, whereas those with SF be delivered ≤ 34 weeks. Our aim was to investigate the validity of this new definition by comparing adverse pregnancy outcomes in SIP with (SIP-SF) and without SF (SIP). Study Design Women with chronic hypertension (CHTN) enrolled in a multicenter trial were studied. SIP was reclassified according to the new definition to SIP and SIP-SF (persistent systolic blood pressure [BP] > 160 or diastolic BP > 110, platelets < 100 K, liver function tests > 70, creatinine > 1.1, or persistent central nervous system/abdominal symptoms). Composite adverse outcomes including rates of indicated preterm birth, abruptio placentae, postpartum hemorrhage, and maternal death were compared by chi-square. Adjustment was done with a multivariate logistic-regression analysis and all statistical tests were two-sided. Results A total of 216 women (28%) out of 774 with CHTN developed SIP, 87 (11%) had SIP-SF, and 129 (17%) didn't have SF. Baseline characteristics including maternal age, baseline BP, and assignment to low-dose aspirin were similar between groups. Using univariate analysis, the composite adverse outcome was higher among the SIP-SF group (p = 0.04), as well as indicated preterm birth (p = 0.02), cesarean section (p = 0.02), and SGA (p = 0.02). After adjustment, composite adverse outcomes were not significantly different between groups. The rate of SGA, however, was higher among SIP-SF (adjusted odds ratio: 3.12, p = 0.02). Conclusion The rate of SIP-SF in this study was 11% of all women with CHTN. Surprisingly, pregnancy outcomes were not significantly different in those with and without SF. We suggest a prospective observational study to determine the optimal timing for delivery in those with SIP using new ACOG diagnostic criteria.


Asunto(s)
Desprendimiento Prematuro de la Placenta/epidemiología , Hipertensión/fisiopatología , Mortalidad Materna , Hemorragia Posparto/epidemiología , Preeclampsia/fisiopatología , Nacimiento Prematuro/epidemiología , Adulto , Presión Sanguínea , Enfermedades del Sistema Nervioso Central/etiología , Enfermedad Crónica , Comorbilidad , Creatinina/sangre , Femenino , Humanos , Hipertensión/complicaciones , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Pruebas de Función Hepática , Recuento de Plaquetas , Embarazo , Resultado del Embarazo/epidemiología , Índice de Severidad de la Enfermedad
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