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1.
Cell Death Differ ; 23(6): 1060-72, 2016 06.
Article in English | MEDLINE | ID: mdl-26846144

ABSTRACT

Akt activation has been associated with proliferation, differentiation, survival and death of epithelial cells. Phosphorylation of Thr308 of Akt by phosphoinositide-dependent kinase 1 (PDK1) is critical for optimal stimulation of its kinase activity. However, the mechanism(s) regulating this process remain elusive. Here, we report that 14-3-3 proteins control Akt Thr308 phosphorylation during intestinal inflammation. Mechanistically, we found that IFNγ and TNFα treatment induce degradation of the PDK1 inhibitor, 14-3-3η, in intestinal epithelial cells. This mechanism requires association of 14-3-3ζ with raptor in a process that triggers autophagy and leads to 14-3-3η degradation. Notably, inhibition of 14-3-3 function by the chemical inhibitor BV02 induces uncontrolled Akt activation, nuclear Akt accumulation and ultimately intestinal epithelial cell death. Our results suggest that 14-3-3 proteins control Akt activation and regulate its biological functions, thereby providing a new mechanistic link between cell survival and apoptosis of intestinal epithelial cells during inflammation.


Subject(s)
14-3-3 Proteins/metabolism , Proto-Oncogene Proteins c-akt/metabolism , 14-3-3 Proteins/antagonists & inhibitors , 3-Phosphoinositide-Dependent Protein Kinases/antagonists & inhibitors , 3-Phosphoinositide-Dependent Protein Kinases/metabolism , Animals , Apoptosis/drug effects , Autophagy/drug effects , Benzamides/pharmacology , Cell Line , Colitis/chemically induced , Colitis/metabolism , Colitis/pathology , Epithelial Cells/cytology , Epithelial Cells/metabolism , Interferon-gamma/pharmacology , Intestinal Mucosa/cytology , Male , Mice , Mice, Inbred C57BL , Microscopy, Fluorescence , Phosphorylation/drug effects , Protein Kinase Inhibitors/pharmacology , Protein Subunits/antagonists & inhibitors , Protein Subunits/metabolism , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Pyrazoles/pharmacology , Signal Transduction/drug effects , Threonine/metabolism
2.
Acta Ortop Mex ; 28(5): 315-8, 2014.
Article in Spanish | MEDLINE | ID: mdl-26021097

ABSTRACT

INTRODUCTION: Multiple cervical spine fractures are a relatively infrequent entity and thus the available information on them is scarce worldwide. The cases reported are usually managed conservatively, with a combination of skeletal traction and various braces, with variable results. There are only a few reports of multiple fractures treated surgically. Objective: This is a report of a clinical case of a multiple cervical fracture treated surgically in 2 stages at the Mexico City Center for Patients with Spine and Spinal Cord Injury (Centro de Atenci6n a Lesionados Raquimedulares de la Ciudad de Mexico), located at "La Villa" General Hospital, SSDF. MATERIAL AND METHODS: We report the clinical case of a male, 46 year-old patient involved in a motor vehicle accident who sustained spine and spinal cord injuries consisting of ASIA C C2-C6 fractures. It was decided to perform two-stage surgery with posterior and anterior instrumentation. We report the 19-month clinical and radiological follow-up. RESULTS: In the 19-month follow-up visit, the patient was found to be ASIA D according to the neurological assessment, with mild motor deficit of the left thoracic limb. The patient had returned to his usual job and had acceptable cervical spine mobility. CONCLUSIONS: The patient's appropriate course from the neurological perspective and his return to his daily activities leads to recommending the surgical management of multiple fractures, customizing it in each case according to the fractures' characteristics. Favorable results may be expected from this approach.


Subject(s)
Multiple Trauma , Spinal Fractures , Humans , Male , Middle Aged , Multiple Trauma/diagnostic imaging , Multiple Trauma/surgery , Radiography , Spinal Fractures/diagnostic imaging , Spinal Fractures/surgery
3.
Acta Ortop Mex ; 25(6): 366-71, 2011.
Article in Spanish | MEDLINE | ID: mdl-22512100

ABSTRACT

BACKGROUND: Knowledge of the morphometric anatomy of cervical pedicles is essential for the safe and accurate placement of pedicle screws during instrumentation of the cervical spine. Screw placement in the lumbar and thoracic vertebrae is considered as a safe practice, unlike the cervical vertebrae due to the risks involved. There are few reports on this technique. The little available information comes from populations different from the Mexican population. Knowing the measurements of each cervical vertebra will provide proper screw orientation and selection at the time of screw placement. METHODS: Prospective, cross-sectional, descriptive study in subjects who presented at the outpatient and emergency services. Patient's in whom a CAT scan of the cervical spine was ordered as part of the work-up protocol, from April 1st 2010 to October 31st 2010, were included. A morphometric anatomic study was undertaken using the CAT software. In a saggital view: a) Saggital angle, b) Saggital diameter. In an axial view: a) Work distance, b) Cross-sectional angle and c) Cross-sectional diameter. RESULTS: The following measurements were obtained for each segment from C2 to C7: mean, standard deviation, range and minimal and maximal values. CONCLUSIONS AND CLINICAL RELEVANCE: Appropriate preoperative planning prior to cervical transpedicular instrumentation is essential to achieve greater accuracy during screw placement. The information obtained allows performing the procedure. As a result of this, a report based on out center's experience may be disseminated thus sharing our technique with the medical community.


Subject(s)
Cervical Vertebrae/anatomy & histology , Adolescent , Anthropometry , Cross-Sectional Studies , Humans , Mexico , Prospective Studies
4.
Bol Med Hosp Infant Mex ; 46(7): 455-62, 1989 Jul.
Article in Spanish | MEDLINE | ID: mdl-2788434

ABSTRACT

We studied the frequency of isolation and antimicrobial susceptibility of strict anaerobic bacteria isolated in a paediatric hospital. A total of 1,753 samples from purulent material and hemocultures were processed. One hundred and thirty strains were isolated from 95 children: 44 from 48 cases of peritonitis (91.7%), 2 from 8 brain abscesses (25%), 23 from 124 soft tissue abscesses (18.5%), 4 from 64 empyemas or lung abscesses (6.3%) and 22 from 1,509 hemocultures (1.5%). Mixed infection (anaerobic and aerobic bacteria) was detected in 38.5% of the cases; however, in peritonitis 81.3% of the cases showed mixed infection. The more frequently isolated bacteria were: Bacteroides (44.6%), Clostridium (19.2%), Fusobacterium (7.7%) and gram positive cocci (7.7%). Propionibacterium acnes was isolated in 15 specimens; however, most of them were considered as contamination. Bacteroides was isolated more frequently from patients with peritonitis (51.6%). The susceptibility to five antibiotics was tested in 124 strains using the method of serial dilutions in agar plates. The genus Bacteroides showed a high resistance to penicillin (73.1%), moderate to clindamycin (11.5%) and low to cefoxitin, chloramphenicol and metronidazole (6.8%, 2% and 5.8%). The rest of the anaerobic strains tested (other gram negatives and grampositives) were highly sensitive to all the antimicrobials tested, except for clindamycin (26.7% and 36.9% resistance, respectively). Cefoxitin, chloramphenicol and metronidazole had the lower CMI50 and CMI90 for the genus Bacteroides; and for the rest of the bacteria, penicillin had the highest activity (CMI90 less than 0.025). Since the frequency of isolation of anaerobic bacteria in children with severe infections, presumably originated from the digestive tract, paranasal sinus and middle ear is high, anaerobic cultures must be practiced in these patients. Empiric antimicrobial treatment should also be started. This treatment should be with penicillin when the probability of isolation of Bacteroides is low (infections in the face, neck, thorax and soft tissues) and with metronidazole in intraabdominal infections. Because of the severity and probable etiology of brain abscesses, treatment with penicillin and chloramphenicol or metronidazole is recommended in these cases.


Subject(s)
Bacteria, Anaerobic/isolation & purification , Bacterial Infections/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteria, Anaerobic/drug effects , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , Child , Cross Infection/epidemiology , Cross-Sectional Studies , Drug Resistance, Microbial , Humans , Mexico , Microbial Sensitivity Tests
6.
Bol. méd. Hosp. Infant. Méx ; 41(5): 262-7, 1984.
Article in Spanish | LILACS | ID: lil-21497

ABSTRACT

Con el objeto de evaluar la tecnica de coaglutinacion para el diagnostico de la meningoencefalitis por Haemophilus influenzae y por Streptococcus pneumoniae se estudiaron 231 muestras do liquido cefalorraquideo: 41 con cultivo positivo para H.influenzae, 17 por Str. pneumoniae, 85 de ninos con meningitis purulenta sin germen aislado y 88 de un grupo testigo.Se encontro una sensibilidad de 87.8 por ciento para H. influenzae y de 82.3 por ciento para Sr. pneumoniae con valor predictivo negativo de 95.4 y 90.1 por ciento respectivamente. La especificidad y valor predictivo positivo fue del ciento por ciento para ambos germenes. En el 38.8 por ciento de los LCR de ninos em meningitis purulenta sin germen aislado, se logro identificar antigenos de H. influenzae o Str.pneumoniae.La coaglutinacion persistio positiva en la mayoria de los casos, a pesar de la administracion de antimicrobianos durante varios dias


Subject(s)
Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Humans , Haemophilus influenzae , Meningoencephalitis , Streptococcus pneumoniae , Cerebrospinal Fluid
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