Mitochondrial dysfunction occurs before transport or tight junction deficits in biliary epithelial cells exposed to bile from methylenedianiline-treated rats.

Methylenedianiline (DAPM) rapidly injures biliary epithelial cells (BEC) in vivo. Prior to evident BEC injury, biliary glucose and inorganic phosphate appreciably rise, which could stem from loosened tight junctions (TJ). Concurrently, ultrastructural abnormalities in BEC mitochondria of DAPM-treated animals are observed, suggesting other impairments. Our objective was to develop an in vitro BEC model to assess the time course of impairments in TJ integrity, glucose uptake, and mitochondrial function following DAPM exposure. We exposed monolayers of primary, polarized rat BEC to bile collected from rats prior to (Basal Bile) or after oral treatment (DAPM-Bile) with 50 mg DAPM/kg. DAPM-Bile collected during 0-60 min (1st Hr) and during 61-120 min (2nd Hr) after treatment was pooled from four to six rats. When monolayers were exposed to 1st Hr DAPM-Bile for 120 min, metabolic activity (XTT assay) decreased approximately 75%, and transepithelial resistance decreased approximately 16% in agreement with an approximately 65% increase in leakage of a glucose analog, methyl-alpha-D-glucopyranoside (AMG), from apical to basolateral media. By 60 min, AMG uptake was decreased approximately 40%. Mitochondrial function was very rapidly compromised, with approximately 120% increases in the green-to-red fluorescence ratio of JC-1 (mitochondrial membrane potential dye) at 15 min and approximately 55% decreases in ATP levels at 30 min. This sequence of events indicates that DAPM impairs BEC mitochondria prior to impairments in glucose uptake or TJ integrity. Thus, our in vitro primary rat BEC/bile exposure model mimics in vivo observations and yields basic information about the time course of events that occur during DAPM-induced injury.     

Tolerabilidad y efectividad del citrato de fentanilo oral transmucosa en el tratamiento a largo plazo del dolor irruptivo en pacientes oncológicos: estudio ECODIR

INTRODUCTION: Oral trans-mucosal fentanyl citrate (OTFC) is the one drug specifically developed for the management of breakthrough pain. This study assesses the long-term safety and efficacy of OTFC standard clinical conditions. Patients and methods. Six-month observational study performed on cancer patients with episodes of breakthrough pain. Safety was assessed by recording the advent of adverse events and efficacy by the evaluating the intensity of breakthrough pain. RESULTS: 174 cancer patients were recruited into the study. All adverse reactions reported were mild or moderate. OTFC was significantly faster (time to the commencement of pain relief: 12.7 +/- 11.4 vs 32.7 +/- 18.4 minutes; p < 0.001) and potent (post-treatment pain intensity: 3.4 +/- 1.5 vs 4.3 +/- 1.5; p < 0.001) than the previously-used drugs. CONCLUSIONS: This observational study confirms the good safety profile of OTFC as well as its effectiveness over long-term period treatment of breakthrough pain.     

Oftalmoplejía completa izquierda por metástasis ósea de cáncer de próstata

Prognosis in prostate cancer is determined, in greater part, by the presence of metastases. Bone metastases can occur in any part of the skeleton even, for example, at the base of the skull. We present a case of a 78 year old male who, in December 2001, presented with paralysis of the third cranial nerve. The NMR and CAT scans were normal and circulating levels of PSA were elevated. He was referred to the Urology Service where the treatment guidelines included complete androgen block. Subsequently, he developed retro-orbital pain, divergent strabismus and palpebral ptosis. CAT and NMR indicated a soft tissue mass at the sphenoid level. Treatment was Gamma Knife Radio-surgery. Since August 2004, in conjunction with the latest rise in PSA, the patient's general status deteriorated considerably and he was referred to the Oncology Service. there was an increase in the paralysis of the third, fourth and sixth cranial nerve (complete left ophthalmoplegia) and left-central facial paralysis. Metastases from prostate cancer can be disseminated via the lymphatic or the blood system. Currently, there are more metastases from large-size tumours. Metastases are critical in prostate cancer because of their adverse effect on the patient's survival. Measurements of circulating levels of prostate specific antigen and prostate acid phosphatase are very useful in the clinical diagnosis of the primary tumour, or its metastases.     

Locoregional anesthesia for external ear surgery and postoperative analgesia

OBJECTIVES: To evaluate a change in the classical technique for local-regional anesthesia (periauricular "V" infiltration) for surgery on the outer ear, specifically adding a new infiltration of the osteocartilaginous juncture of the external acoustic meatus and the auditory foramen, as an alternative to general anesthesia in adults, including assessment of postoperative analgesia. PATIENTS AND METHODS: The new technique was used in 45 operations on 23 patients. We analyzed pain during and after surgery on a simple verbal scale. RESULTS: After modifying the technique it was possible to perform surgery on the outer ear without causing pain, patients reporting "0" pain on a scale of 0 to 10. Eight patients reported "0" for postoperative pain, while one assessed pain as "4" and one as "2". No signs of emesis or cardiac events were observed. CONCLUSIONS: The described local-regional blockade of the outer ear used as the only anesthetic method, is indicated for both cosmetic surgery and repair of outer ear injuries, given its excellent analgesia during and after surgery. The characteristics of this type of block of the pavilion make it ideal for major outpatient surgery and a valid alternative to general anesthesia in adults.     

Efficacy of a single dose of urapidil for preventing arterial hypertension during the pre-bypass period in coronary surgery

OBJECTIVES: To assess the effect of a single prophylactic dose of urapidil for arterial hypertension during the period before start of extracorporeal circulation. PATIENTS AND METHODS: Forty-four patients with good ventricular function (ejection fraction < 40%) scheduled for coronary surgery were enrolled for prospective study. The patients were randomly assigned to receive 0.5 mg/kg of urapidil (group U, n = 22) or nothing (group N, n = 22) 3 min before skin incision. If hypertension developed sodium nitroprusside was administered, starting with a dose of 0.5 microgram/kg/min. Monitoring of arterial pressure, heart rate and ST segment (DII and V5) was continuous. The study ended with cannulation of the aorta. RESULTS: The demographic features, cardiovascular history, medication and duration of surgery were comparable in the two groups. Six patients in group U (27%) and 19 in group N (86%) developed arterial hypertension (p < 0.001), the duration of which was 2.23 +/- 4.49 min in group U and 9.64 +/- 9.7 min in group N (p < 0.05). Arterial hypotension was observed in 13 group U patients and 7 group N patients (NS). No significant differences in duration of tachycardia, bradycardia or myocardial ischemia were found. CONCLUSIONS: The administration of a single dose of urapidil prevents arterial hypertension during the phase before extracorporeal circulation for coronary surgery and reduces the need for nitroprusside. No clinically relevant side effects are evident.     

Executive function and general intellectual functioning in dyskinetic cerebral palsy: Comparison with spastic cerebral palsy and typically developing controls

AimTo comprehensively describe intellectual and executive functioning (EF) in people with dyskinetic cerebral palsy (DCP), by comparing their performance with that of: 1) age- and sex-matched typically developing controls (TDC); and 2) participants with spastic cerebral palsy (SCP) matched for age, sex, term/preterm and gross motor function classification system (GMFCS).MethodThis cross-sectional study was conducted by the University of Barcelona in collaboration with five institutions. Participants were people with DCP (n = 52; 24 females, median age 20.5 y: 5mo, interquartile range [IQR] = 13.75 y: 7mo; GMFCS I–V). As comparison groups, participants with SCP (n = 20; 10 females, median age = 20.5 y: 5.5mo, IQR = 13.75 y 9mo; GMFCS I–V) and TDC (n = 52; 24 females, median age = 20 y: 4mo, IQR = 12 y 7mo) were included. Intelligence and EF were assessed using common tests in all participants.ResultsBoth CP groups had lower intelligence than TDC and performed poorer in almost all EF tasks. Intelligence was higher in DCP than SCP (z = ?2.51, p = 0.01). Participants with DCP also performed significantly better in goal-setting tasks (z = 2.27, p = 0.03) and information processing (z = ?2.54, p = 0.01) than those with SCP.ConclusionPeople with DCP present lower general intellectual functioning and poorer EF across multiple domains than typically developing controls. People with DCP have higher general intellectual functioning and better EF than people with SCP when levels of motor severity are similar.     

The effects of hyperammonemia in learning and brain metabolic activity

Ammonia is thought to be central in the development of hepatic encephalopathy. However, the specific relation of ammonia with brain energy depletions and learning has not been studied. Our work attempts to reproduce an increase in rat cerebral ammonia level, study the hyperamonemic animals’ performance of two learning tasks, an allocentric (ALLO) and a cue guided (CG) task, and elucidate the contribution of hyperammonemia to the differential energy requirements of the brain limbic system regions involved in these tasks. To assess these goals, four groups of animals were used: a control (CHA) CG group (n?=?10), a CHA ALLO group (n?=?9), a hyperammonemia (HA) CG group (n?=?7), and HA ALLO group (n?=?8). Oxidative metabolism of the target brain regions were assessed by histochemical labelling of cytochrome oxidase (C.O.). The behavioural results revealed that the hyperammonemic rats were not able to reach the behavioural criterion in either of the two tasks, in contrast to the CHA groups. The metabolic brain consumption revealed increased C.O. activity in the anterodorsal thalamus when comparing the HA ALLO group with the CHA ALLO group. Significant differences between animals trained in the CG task were observed in the prelimbic, infralimbic, parietal, entorhinal and perirhinal cortices, the anterolateral and anteromedial striatum, and the basolateral and central amygdala. Our findings may provide fresh insights to reveal how the differential damage to the brain limbic structures involved in these tasks differs according to the degree of task difficulty.