Umbilical cord mesenchymal stromal cells transplantation delays the onset of hyperglycemia in the RIP-B7.1 mouse model of experimental autoimmune diabetes through multiple immunosuppressive and anti-inflammatory responses.

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder specifically targeting pancreatic islet beta cells. Despite many efforts focused on identifying new therapies able to counteract this autoimmune attack and/or stimulate beta cells regeneration, TD1M remains without effective clinical treatments providing no clear advantages over the conventional treatment with insulin. We previously postulated that both the inflammatory and immune responses and beta cell survival/regeneration must be simultaneously targeted to blunt the progression of disease. Umbilical cord-derived mesenchymal stromal cells (UC-MSC) exhibit anti-inflammatory, trophic, immunomodulatory and regenerative properties and have shown some beneficial yet controversial effects in clinical trials for T1DM. In order to clarify conflicting results, we herein dissected the cellular and molecular events derived from UC-MSC intraperitoneal administration (i.p.) in the RIP-B7.1 mouse model of experimental autoimmune diabetes. Intraperitoneal (i.p.) transplantation of heterologous mouse UC-MSC delayed the onset of diabetes in RIP-B7.1 mice. Importantly, UC-MSC i. p. transplantation led to a strong peritoneal recruitment of myeloid-derived suppressor cells (MDSC) followed by multiple T-, B- and myeloid cells immunosuppressive responses in peritoneal fluid cells, spleen, pancreatic lymph nodes and the pancreas, which displayed significantly reduced insulitis and pancreatic infiltration of T and B Cells and pro-inflammatory macrophages. Altogether, these results suggest that UC-MSC i. p. transplantation can block or delay the development of hyperglycemia through suppression of inflammation and the immune attack.

Algoritmo de manejo de la vía aérea en la paciente obstétrica / Airway management algorithm in the obstetrics patient

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Algoritmo de la vía aérea difícil en pediatría / No disponible

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Sección completa del ciático poplíteo externo durante una meniscectomía externa por artroscopia / Complete section of the external popliteal sciatic nerve during arthroscopic lateral meniscectomy

Objetivo: Comunicar la lesión del nervio ciático poplíteo externo (CPE) como complicación inusual tras una artroscopia de rodilla. Caso clínico: Presentamos el caso clínico de un paciente que presenta una sección completa del nervio CPE, tras una meniscectomía externa por artroscopia, que precisó la realización de injerto nervioso para conseguir la recuperación. Discusión: Las lesiones neurológicas tras la artroscopia de rodilla son infrecuentes, no hemos encontrado un caso de sección completa con pérdida de continuidad neurológica tras una meniscectomía y existen casos publicados similares que son comentados. Conclusiones: Aunque infrecuente, es posible la lesión de estructuras nerviosas durante la práctica de una artroscopia de rodilla (AU)

Purpose: The aim of this paper is to present a case of external popliteal sciatic nerve injury, which is an unusual complication following knee arthroscopy. Clinical case: We present the case of a patient who suffered a complete rupture of the external popliteal sciatic nerve (EPSN), following arthroscopic lateral meniscectomy, which required the use of a nerve graft to facilitate recovery. Discussion: Nerve lesions following knee arthroscopy are rare. We have found no instances of complete nerve rupture accompanied by a break in neurologic continuity following meniscectomy. We have however found a few similar cases, which we report on in the paper. Conclusions: Although uncommon, injury to nerve structures is possible during knee arthroscopy (AU)

Bortezomib decreases Rb phosphorylation and induces caspase-dependent apoptosis in Imatinib-sensitive and -resistant Bcr-Abl1-expressing cells.

The use of c-abl-specific inhibitors such as Imatinib (IM) or Dasatinib has revolutionized the treatment of chronic myeloid leukemia (CML). However, a significant percentage of patients become resistant to IM. In this report, we have analyzed the possibility of using the proteasome as a molecular target in CML. Our results show that cells that express Bcr-Abl1 are more sensitive to the inhibition of the proteasome with Bortezomib (Btz) than control cells. This treatment reduces the proliferation of Bcr-Abl1-expressing cells, by inactivating NF-kappaB2 and decreasing the phosphorylation of Rb, eventually leading to an increase in caspase-dependent apoptosis. Furthermore, we show that Btz also induces cell-cycle arrest and apoptosis in cells expressing Bcr-Abl1 mutants that are resistant to IM. These results unravel a new molecular target of Btz, that is the Rb pathway, and open new possibilities in the treatment of CML especially for patients that become resistant to IM because of the presence of the T315I mutation.

Short-term exposure to sublethal tebuconazole induces physiological impairment in male zebrafish (Danio rerio).

The aim of the present study was to assess the physiological response of male zebrafish Danio rerio to the fungicide tebuconazole and recovery in fungicide-free water. Acute toxicity tests were carried out and the median lethal concentration (LC(50)) from 24 to 96 h was calculated. The fish were exposed to a sublethal fungicide concentration of 230 microg/L for 7 or 14 days and allowed to recover for 7 or 14 more days, respectively. Whole-body levels of vitellogenins, triglycerides, cholesterol, glucose, lactate and proteins as well as the activities gamma-glutamil transpeptidase (gamma-GT), alanin aminotransferase (AlAT), alkaline phosphatase (AP) and lactate dehydrogenase (LDH) were assayed; corpulence factor (k) was also calculated. Fish exhibited significant increase of vitellogenins (Vtg), which continued to increase after 14 days of recovery. Levels of glucose, lactate, cholesterol and triglycerides increased after 7 and 14 days of exposure. Finally, cholesterol and glucose recovered after 14 days of recovery whereas triglycerides and lactate continued to be elevated. Proteins and k remained unaltered the entire experiments. AAT, AlAT and AP enhanced during exposure and did not recover at the end (except AlAT). A longer recovery period should be necessary to re-establish fish physiology. These results alert about the multiple disruptive physiological actions that tebuconazole may have on fish.

Combined closed avulsion of the central slip and terminal tendon of the finger extensor mechanism.

This clinical case describes a patient who suffered a combined closed avulsion of the central slip and the terminal tendon of the index finger extensor mechanism, associated with a unicondylar fracture of the middle phalanx and a spiroid fracture of the second metacarpal.

Disturbances in energy metabolism of Daphnia magna after exposure to tebuconazole.

This study was conducted to investigate the change of some biochemical parameters in the aquatic invertebrate Daphnia magna following exposure to the fungicide tebuconazole and to determine the most sensitive biomarker among the ones tested in this species. Four biochemical biomarkers (protein, glycogen, lipids and caloric content) were correlated with feeding behaviour studies of D. magna after fungicide exposure. Juveniles of D. magna were exposed to four sublethal concentrations of tebuconazole (0.41, 0.52, 0.71 and 1.14 mgL(-1)) for 5d. Daphnid samples were taken from each test and control group at 24, 48, 72, 96 and 120 h after the start of the experiment. Tebuconazole EC(50) values were calculated on D. magna in our laboratory as 56.83 and 40.10 mgL(-1) at 24 and 48 h, respectively. Results showed that daphnid energy content decreased as tebuconazole concentration increased, especially after 96-120 h of exposure to 0.52 mgL(-1) and higher fungicide concentrations. The data suggest that tebuconazole is moderately toxic to D. magna but also that it seriously impairs the metabolic functions, resulting in alterations in biochemical constituents. In the D. magna feeding study, algae feeding rates were inhibited after fungicide exposure. Such findings indicate the importance of feeding studies in laboratory toxicity test as well as their relationship with others studies. The results emphasize the importance of considering different kind of biomarkers to identify and evaluate the biological effect of a fungicide in the aquatic environment. Although the biochemical biomarkers used resulted good indicators of tebuconazole toxicity, feeding rates in D. magna decreased after only 5h exposure to the fungicide resulting in the most sensitive parameter of daphnid fungicide exposure.

Effects of propanil on the European eel Anguilla anguilla and post-exposure recovery using selected biomarkers as effect criteria.

The aim of this study was to assess the physiological response of Anguilla anguilla to propanil and the degree of recovery after being moved to clean water. Preliminary acute toxicity test was carried out in the laboratory and the median lethal concentration (LC50) at 96 h was calculated as 31.33 mg/L (29.60-33.59 mg/L). NOEC and LOEC values (at 96 h) were also calculated as 20 and 25mg/L, respectively. The fish were exposed to 0.63 and 3.16 mg/L of propanil for 72 h and allowed to recover for 144 h. Total proteins (TPs), gamma-glutamil transpeptidase (gamma-GT), alanin aminotransferase (AlAT), alkaline phosphatase (AP), lactate dehydrogenase (LDH) and water content (WC) were assayed in muscle and liver tissues, liver somatic index (LSI) was also determined. Liver TPs and gamma-GT activity decreased after propanil exposure while AlAT and LDH increased. Muscular AP, AlAT and proteins decreased in intoxicated eels while LDH and gamma-GT activities increased. WC increased in both tissues after herbicide exposure as well as LSI. These results revealed that propanil affects the intermediary metabolism of A. anguilla and that the assayed enzymes can be used as good biomarkers of herbicide contamination. However a longer recovery period should be necessary to re-establish eel physiology. The parameters measured in the present study can be used as herbicide toxicity indicators and are recommended for environmental monitoring assessments.

[Fetoscopic tracheal occlusion for the treatment of severe congenital diaphragmatic hernia: preliminary results]. / Oclusión traqueal fetoscópica (FETO) para el tratamiento de la hernia diafragmática congénita severa: resultados preliminares.

OBJECTIVES: To evaluate survival and lung growth in fetuses with severe congenital diaphragmatic hernia (CDH) treated with fetoscopic tracheal occlusion (FETO) compared with control fetuses and to analyze possible complications of the anesthetic techniques used. PATIENTS AND METHODS: This prospective study was performed on fetuses with CDH. FETO was undertaken before the 29th week of gestation on fetuses with a lung-to-head ratio (LHR) less than 1. FETO was not performed on fetuses with an LHR between 1.0 and 1.5 or those with an LHR less than 1 where consent was not given. Lung growth was monitored by means of LHR. FETO was performed under fetal intramuscular anesthesia and maternal epidural anesthesia and sedation with remifentanil. RESULTS: Seventeen fetuses were included in the study. FETO was performed on 11 fetuses and was effective in 9. The median percentage difference between LHR at diagnosis and prior to FETO was 1.15% (P=.183); between diagnosis and before removing the balloon, the difference was 130.5% (P=.003); and between diagnosis and before delivery, 90.18% (P=.003). In the control group (n=6), the median percentage difference between LHR at diagnosis and before delivery was 49.25% (P=.028). No significant hemodynamic or respiratory changes occurred in either mother or fetus during fetoscopy. All the fetuses in the control group died; 45.5% of those in the FETO group survived. CONCLUSIONS: The use of FETO in cases of CDH appears to increase survival and lung growth. Fetal anesthesia in association with maternal epidural anesthesia and sedation makes it possible to place and remove the endotracheal balloon via fetoscopy with acceptable maternal comfort and without notable complications.

Oclusión traqueal fetoscópica (FETO) para el tratamiento de lahernia diafragmática congénita severa: resultados preliminares / Fetoscopic tracheal occlusion for the treatment of severe congenital diaphragmatic hernia: preliminary results

OBJETIVOS: Evaluar la supervivencia y crecimientopulmonar de fetos con hernia diafragmática congénitasevera (HDCs) tratados con oclusión traqueal fetoscópica(FETO) comparado con aquellos en que no se realizóy analizar posibles complicaciones de las técnicas anestésicas.PACIENTES Y MÉTODOS: Estudio prospectivo en fetoscon HDCs. FETO fue realizada antes de la 29 SG a fetoscon un lung head ratio (LHR) < 1. No se realizó FETO alos pacientes con LHR entre 1,0 y 1,5 o con LHR<1 queno dieron consentimiento. El crecimiento pulmonar fuemonitorizado con el LHR. Las fetoscopias se realizaronbajo anestesia intramuscular fetal asociada a anestesiaepidural y sedación materna con remifentanilo.RESULTADOS: Se incluyeron 17 fetos. En 11 se realizóFETO que fue efectiva en 9, la mediana de la diferenciade porcentajes del LHR respecto al diagnóstico fue1,15% (p = 0,183) previamente FETO, 130,5% (p =0,003) antes de retirar el balón y 90,18% (p = 0,003)antes del parto. En los “no FETO” (n=6) la diferencia deporcentajes del LHR antes del parto respecto al diagnósticofue 49,25% (p = 0,028). Durante las fetoscopiasno se produjeron cambios significativos hemodinámicoso respiratorios maternos ni fetales. En el grupo "FETO" 45,5% sobrevivieron mientras que en el "no FETO" todos murieron. CONCLUSIONES: FETO en la HDCs parece aumentar lasupervivencia y el crecimiento pulmonar. La anestesiafetal asociada a anestesia epidural y sedación maternapermiten colocar y retirar el balón endotraqueal fetoscópicamentecon buena confortabilidad materna sin complicacionesimportantes (AU)

OBJECTIVES: To evaluate survival and lung growth infetuses with severe congenital diaphragmatic hernia(CDH) treated with fetoscopic tracheal occlusion(FETO) compared with control fetuses and to analyzepossible complications of the anesthetic techniques used.PATIENTS AND METHODS: This prospective study wasperformed on fetuses with CDH. FETO was undertakenbefore the 29th week of gestation on fetuses with a lungto-head ratio (LHR) less than 1. FETO was notperformed on fetuses with an LHR between 1.0 and 1.5or those with an LHR less than 1 where consent was notgiven. Lung growth was monitored by means of LHR.FETO was performed under fetal intramuscularanesthesia and maternal epidural anesthesia andsedation with remifentanil.RESULTS: Seventeen fetuses were included in thestudy. FETO was performed on 11 fetuses and waseffective in 9. The median percentage difference betweenLHR at diagnosis and prior to FETO was 1.15%(P=.183); between diagnosis and before removing theballoon, the difference was 130.5% (P=.003); andbetween diagnosis and before delivery, 90.18% (P=.003).In the control group (n=6), the median percentagedifference between LHR at diagnosis and before deliverywas 49.25% (P=.028). No significant hemodynamic orrespiratory changes occurred in either mother or fetusduring fetoscopy. All the fetuses in the control groupdied; 45.5% of those in the FETO group survived. CONCLUSIONS: The use of FETO in cases of CDHappears to increase survival and lung growth. Fetalanesthesia in association with maternal epidural anesthesiaand sedation makes it possible to place and remove theendotracheal balloon via fetoscopy with acceptablematernal comfort and without notable complications (AU)

[Two cases of congenital airway obstruction managed with ex utero intrapartum treatment procedures: anesthetic implications]. / Dos casos de obstrucción congénita de la vía aérea sometidos a E.X.I.T. ("ex-utero intrapartum treatment"): implicaciones anestésicas.

An ex utero intrapartum treatment (EXIT) procedure provides sufficient time to gain control of the potentially obstructed fetal upper airway while uterine placental circulation is maintained during cesarean section. We report 2 cases in which fetal congenital upper airway obstruction was managed without complications during EXIT procedures. We also discuss general considerations concerning the obstetric patient and the performance of intramuscular fetal anesthesia. Before the hysterotomy, sevoflurane at 1.5 minimum alveolar concentration was administered to assure sufficient uterine relaxation during EXIT. The 2 parturients remained hemodynamically stable during the procedure and uterine and placental perfusion was adequate. Nasotracheal intubation was possible in 1 fetus after a cervical mass was dissected. In the other, a tracheostomy was created. After the umbilical cord was clamped, the concentration of sevoflurane anesthetic gas was reduced and oxytocin and methylergometrine were administered to induce adequate uterine contractions within a few minutes. Both neonates survived the EXIT procedure with no complications.

Dos casos de obstrucción congénita de la vía aérea sometidos a E.X.I.T. ("ex-utero intrapartum treatment"): implicaciones anestésicas / Two cases of congenital airway obstruction managed with ex utero intrapartum treatment procedures: anesthetic implications

El procedimiento E.X.I.T. (“Ex-Utero Intrapartum Treatment”) proporciona un tiempo adecuado para conseguir el control de una vía aérea fetal potencialmente obstruida mientras se mantiene la circulación útero-placentaria durante la cesárea. Describimos dos casos clínicos de fetos con obstrucción congénita de la vía aérea alta en los que la estrategia E.X.I.T. permitió permeabilizar con éxito y sin complicaciones en la vía aérea. Además de tomarse las consideraciones generales de la paciente obstétrica y de realizarse anestesia fetal intramuscular, previamente a la histerotomía se administró sevofluorano a 1,5 CAM para conseguir una adecuada relajación uterina durante el procedimiento. Las dos gestantes permanecieron hemodinámicamente estables durante el procedimiento con una adecuada perfusión útero-placentaria. En un feto la intubación nasotraqueal fue posible tras disecar la masa cervical mientras que en el otro se realizó una traqueostomía. Tras el clampaje del cordón umbilical se redujo la concentración de halogenado y se administraron oxitocina y metilergometrina para conseguir una contracción uterina adecuada en pocos minutos. Ambos neonatos sobrevivieron al procedimiento sin complicaciones

An ex utero intrapartum treatment (EXIT) procedure provides sufficient time to gain control of the potentially obstructed fetal upper airway while uterine placental circulation is maintained during cesarean section. We report 2 cases in which fetal congenital upper airway obstruction was managed without complications during EXIT procedures. We also discuss general considerations concerning the obstetric patient and the performance of intramuscular fetal anesthesia. Before the hysterectomy, sevoflurane at 1.5 minimum alveolar concentration was administered to assure sufficient uterine relaxation during EXIT. The 2 parturients remained hemodynamically stable during the procedure and uterine and placental perfusion was adequate. Nasotracheal intubation was possible in 1 fetus after a cervical mass was dissected. In the other, a tracheostomy was created. After the umbilical cord was clamped, the concentration of sevoflurane anesthetic gas was reduced and oxytocin and methylergometrine were administered to induce adequate uterine contractions within a few minutes. Both neonates survived the EXIT procedure with no complications