Regulation of Hepatocellular Fatty Acid Uptake in Mouse Models of Fatty Liver Disease with and without Functional Leptin Signaling: Roles of NfKB and SREBP-1C and the Effects of Spexin.

The processes causing increased hepatic triglycerides (TGs) in mouse models of hepatic steatosis (HS) due to high fat diet (HFD)-induced obesity (DIO), EtOH consumption, or obesity mutations (ob/ob, db/db) are uncertain. This report summarizes two studies. Study 1 focused on regulation by five transcription factors (TFs) (NfKb, Srebp-lc, AMPK, PPARα, PPARγ) of seven, much-studied hepatic long-chain fatty acid (LCFA) transporters (FABPpm, CD36, FATPl, FATP2, FATP4, FATP5, & Caveolin-1 [CAV-1]), and expression of genes for enzymes of LCFA synthesis (SCD-1, FASN) in mice with HS from various causes. Study 2 examined the effects of spexin, a novel adipokine, on obesity, type 2 diabetes mellitus (T2DM), and HS in these mice. Study 1 showed that: (1) processes underlying HS differed in mice with normal leptin signaling (DIO, EtoH-fed) versus those without it (ob/ob, db/db). Increased hepatocellular LCFA uptake was the principal cause of HS in the former, but increased hepatocellular LCFA synthesis predominated in the latter. (2) Expression of individual transporters was variable in the HS models studied, but strong correlations between TF expression and mean expression of four transporter genes across multiple HS models suggested regulatory interaction, and support the postulate that complexes of several different transporters mediate hepatic LCFA uptake. Study 2 indicated (1) that obese DIO mice often also have T2DM and/or nonalcoholic fatty liver disease (NAFLD); (2) confirmed that spexin treatment caused weight loss in DIO mice; (3) in DIO mice with T2DM, spexin also improved glucose tolerance, decreasing insulin resistance and HbAlc. Incubation with spexin directly inhibited LCFA uptake by hepatocytes isolated from DIO mice with HS/NAFLD by ≤70%. Spexin treatment in vivo for 4 weeks reduced hepatic lipids by 60%, and reduced serum alanine and aspartate aminotransferases. These studies in mice with DIO, T2DM, and HS/NAFLD suggest spexin may be an effective treatment for all three conditions.

Dynamic cystocolpoproctography is superior to functional pelvic MRI in the diagnosis of posterior pelvic floor disorders: results of a prospective study.

AIM: The accuracy of dynamic cystocolpoproctography (DCP) and dynamic MRI were compared in diagnosing posterior pelvic floor disorders. METHOD: Fifty consecutive female patients (mean age 51 years) complaining of posterior compartment pelvic floor disorder and referred to a tertiary centre entered the prospective study. The Institutional Review Board stated that informed consent from the patients was not necessary for this study. Patients underwent a DCP and a supine functional MRI by two different radiologists. Assessment of radiological examinations was prospective and blind. All patients underwent surgery that led to the final diagnosis. Agreement between the operative diagnosis and the diagnoses following DCP and MRI was assessed using the weighted kappa statistic. A matched-pairs McNemar's test was applied to demonstrate whether or not one radiological method was superior to the other. RESULTS: Full-thickness rectal prolapse was best diagnosed by clinical examination. Internal rectal prolapse and peritoneocele were best diagnosed by DCP. A better agreement with the operative diagnosis, which is not true superiority, was observed for DCP compared with functional pelvic MRI for full-thickness rectal prolapse, internal rectal prolapse and peritoneocele. There was no significant difference between DCP and functional pelvic MRI in the diagnosis of internal rectal prolapse (P = 0.125) or peritoneocele (P = 0.10). CONCLUSION: As full-thickness rectal prolapse, internal rectal prolapse and peritoneocele might be missed by functional pelvic MRI, there should still be a place for DCP in particular cases where the clinical diagnosis is not clear in women with symptomatic posterior pelvic floor disorders.

Mental health training experiences among Haitian healthcare workers post-earthquake 2010.

BACKGROUND: After the 2010 earthquake in Haiti, the large number of persons with major limb damage, amputations, shock, trauma, anxiety and depression placed a severe strain on mental health (MH) services. PURPOSE: This qualitative study describes the impact and acceptability of a Mental Health Training Program (MHTP) implemented in the north of Haiti after the earthquake. METHODS: A total of 113 healthcare workers (HCWs) participated in a training program designed to build local MH care capacity. The training curriculum draws on literature related to MH and the impact of the Haiti earthquake. Two focus groups were conducted with 16 HCWs; discussions centred on the personal and professional impact and acceptability of the training program. DISCUSSION: Results demonstrated that the MHTP changed the HCWs' perceptions about MH issues and provided them with the knowledge and skills to respond to growing community MH needs. Acceptability of the MHTP was related to the content covered, to the delivery mode of the content and to the cultural appropriateness of the program. CONCLUSIONS: Disasters of different types will continue to occur and to impact MH in communities around the world. MH training will allow nurses to quickly and effectively respond to disasters. A coordinated emergency plan that is subject to frequent review, rehearsal and evaluation is also essential.

Blood flow vs. venous pressure effects on filtration coefficient in oleic acid-injured lung.

On the basis of changes in capillary filtration coefficient (Kfc) in 24 rabbit lungs, we determined whether elevations in pulmonary venous pressure (Ppv) or blood flow (BF) produced differences in filtration surface area in oleic acid-injured (OA) or control (Con) lungs. Lungs were cyclically ventilated and perfused under zone 3 conditions by using blood and 5% albumin with no pharmacological modulation of vascular tone. Pulmonary arterial, venous, and capillary pressures were measured by using arterial, venous, and double occlusion. Before and during each Kfc-measurement maneuver, microvascular/total vascular compliance was measured by using venous occlusion. Kfc was measured before and 30 min after injury, by using a Ppv elevation of 7 cmH2O or a BF elevation from 1 to 2 l . min-1 . 100 g-1 to obtain a similar double occlusion pressure. Pulmonary arterial pressure increased more with BF than with Ppv in both Con and OA lungs [29 +/- 2 vs. 19 +/- 0.7 (means +/- SE) cmH2O; P < 0. 001]. In OA lungs compared with Con lungs, values of Kfc (200 +/- 40 vs. 83 +/- 14%, respectively; P < 0.01) and microvascular/total vascular compliance ratio (86 +/- 4 vs. 68 +/- 5%, respectively; P < 0.01) increased more with BF than with Ppv. In conclusion, for a given OA-induced increase in hydraulic conductivity, BF elevation increased filtration surface area more than did Ppv elevation. The steep pulmonary pressure profile induced by increased BF could result in the recruitment of injured capillaries and could also shift downstream the compression point of blind (zone 1) and open injured vessels (zone 2).

[Is it useful to maintain specific scores for the early determination of the severity of acute pancreatitis?]. / Faut-il conserver l'utilisation de scores spécifiques pour la détermination précoce de la gravité des pancréatites aiguës?

STUDY AIM: Acute pancreatitis (AP) is a potentially life-threatening disease in which specific severity scoring system has been developed. The aim of this prospective study was to compare efficiency of the general severity of illness scoring system and the most widely used specific scoring system of AP in order to simplify the initial monitoring of AP at the time of admission. PATIENTS AND METHODS: Eighty-seven patients with AP were hospitalized in the same center. There were 47 men and 40 women (mean age: 57 +/- 16 years). Specific scores (Ranson, Imrie, Blarney) and general severity of illness scores (SAPSI, SAPS II, Apache II) were calculated for each patient. Radiological scores (Hill, Balthazar) were also calculated when TDM was early performed (80%). Each scoring system was correlated with severity, morbidity and mortality of AP and its predictive value evaluated by the area under the ROC curve. RESULTS: Aetiology of AP was predominantly biliary (20%) and alcoholic (70%). Eight per cent of the patients died and 29% of AP were classified as severe according to the Atlanta Congress Score. Morbidity rate was 40%. All the scoring systems were significantly correlated with mortality and exhibit ROC curve area between 0.77 and 0.84, resulting in a similar prediction of death. CONCLUSION: Specific scoring system and general severity of illness scoring system have the same predictive efficiency in acute pancreatitis. The use of the specificity scoring system seems to be no more justified in acute pancreatitis.

Chlorine gas induced acute lung injury in isolated rabbit lung.

This study was designed to investigate the pathogenesis of chlorine gas (Cl2) induced acute lung injury and oedema. Isolated blood-perfused rabbit lungs were ventilated either with air (n=7) or air plus 500 parts per million (ppm) of Cl2 (n=7) for 10 min. Capillary pressure, measured by analysing the pressure/time transients of pulmonary arterial, venous and double (both arterial and venous) occlusions, was unchanged in both groups. In Cl2-exposed lungs, the fluid filtration rate increased from -0.228+/-0.25 to 1.823+/-1.23 mL min(-1) x 100 g(-1) (p<0.001) and the filtration coefficient increased from 0.091+/-0.01 to 0.259+/-0.07 mL x min(-1) x cmH2O(-1) x 100 g(-1) (p<0.001). No changes were observed in the control lungs. The extravascular lung water/blood-free dry weight ratio was 8.6+/-1.6 in the Cl2 group and 4.0+/-0.5 in the control group (p<0.001), confirming that the increase in lung weight was related to accumulation of extravascular fluid. Although the alveolar flooding by oedema is explained, in part, by the Cl2-induced epithelial injury, our results suggest that Cl2 exposure induces acute lung injury and oedema due to an increased microvascular permeability.

Time-dependent pressure distortion in a catheter-transducer system: correction by fast flush.

BACKGROUND: Distortion of the pressure wave by a liquid-filled catheter-transducer system leads most often to an overestimation in systolic arterial blood pressure in pulmonary and systemic circulations. The pressure distortion depends on the catheter-transducer frequency response. Many monitoring systems use either mechanical or electronic filters to reduce this distortion. Such filters assume, however, that the catheter-transducer frequency response does not change over time. The current study aimed to study the changes with time of the catheter-transducer frequency response and design a flush procedure to reverse these changes back to baseline. METHODS: An in vitro setup was devised to assess the catheter-transducer frequency response in conditions approximating some of those met in a clinical environment (slow flushing, 37 degrees C, 48-h test). Several flush protocols were assessed. RESULTS: Within 48 h, catheter-transducer natural frequency decreased from 17.89 +/- 0.36 (mean +/- SD) to 7.35 +/- 0.25 Hz, and the catheter-transducer damping coefficient increased from 0.234 +/- 0.004 to 0.356 +/- 0.010. Slow and rapid flushing by the flush device built into the pressure transducer did not correct these changes, which were reversed only by manual fast flush of the transducer and of the catheter. These changes and parallel changes in catheter-transducer compliance may be explained by bubbles inside the catheter-transducer. CONCLUSIONS: Catheter-transducer-induced blood pressure distortion changes with time. This change may be reversed by a manual fast flush or "rocket flush" procedure, allowing a con. stant correction by a filter.

In vivo measurement of lung capillary-alveolar macromolecule permeability by saturation bronchoalveolar lavage.

OBJECTIVE: Measurement of capillary-alveolar permeability to fluorescein isothiocyanate-dextran (FITC-D) (molecular mass, 71,300 daltons) by a sequential bronchoalveolar lavage (BAL) technique. DESIGN: Animal research. SETTING: The Department of Physiology at a scientific and medical university. SUBJECTS: Nine anesthetized and mechanically ventilated dogs. INTERVENTIONS: Two separate experiments were performed in each subject-an initial control experiment followed by an oleic acid-induced lung injury. The indicator was administered at constant blood concentration before serial BAL including eight fluid instillation-recovery cycles. MEASUREMENTS: Plasma to BAL solute clearance at saturation (capillary-alveolar clearance at saturation, mL/min) was calculated and normalized to lavage fluid volume (measured by 1251 serum albumin dilution) to obtain a transport rate (TR) constant. MAIN RESULTS: TR for FITC-D70 was 4.0+/-0.8 and 46.1+/-18.1 x 10(-5) x min(-1) in control and injured lung, respectively (p < .02). Capillary-alveolar clearance of FITC-D70 was not affected by the lavage procedure itself. TR reflected essentially epithelial permeability in normal lung and combined epithelial and endothelial permeability in injured lung. A significant correlation was found between cardiac output and TR in injured lung. CONCLUSIONS: Saturation BAL allowed us to estimate capillary-alveolar macromolecule permeability in vivo in dogs. Further study may allow bedside evaluation of lung injury by BAL in patients.

In vivo quantitation of epithelial lining fluid in dog lung.

We used an original saturation bronchoalveolar lavage (SBAL) technique (Eur. Respir. J. 1995;8[Suppl. 19]398S) to quantitate lung epithelial lining fluid volume (VELF) in dogs in two separate experiments: control and after oleic-acid-induced injury. We confirmed the hypothesis that 99mTc-DTPA, infused at constant plasma activity, reaches equilibrium with epithelial lining fluid after 90 min. We performed eight sequential lavages 215 min after beginning the infusion of 99mTc-DTPA. 99mTc-DTPA activity (Qn) in the lavage fluid increased linearly with time, suggesting transport from the plasma into the alveoli during lavage. We extrapolated Qn to time zero (Q0), when 99mTc-DTPA was not affected by lavage. VELF was calculated from: VELF = Q0/Cp, (Cp: 99mTc-DTPA mean plasma activity). 125I-albumin was used as a nondiffusible alveolar indicator to measure the fluid volume present in the lavaged segment (Vt,n). Vt,n plateaud for n >= 4. VELF/Vt,n(n = 5,8) was 1.7 +/- 0.4 and 25.0 +/- 4.4% (p < 0.05) in control and injury experiments, respectively. SBAL allowed reliable measurements of VELF and detection of alveolar edema fluid in the injured lung.

Comparison of 99mTc-DTPA and urea for measuring cefepime concentrations in epithelial lining fluid.

The efficacy of antimicrobial agents against pulmonary infections depends on their local concentrations in the lung. The aims of the present study were to: 1) compare technetium-99m diethylenetriaminepenta-acetic acid (99mTc-DTPA) and urea as markers of epithelial lining fluid (ELF) dilution for measuring ELF concentrations of pharmaceuticals; 2) quantify ELF cefepime concentrations in normal and injured lung; and 3) measure the increase in permeability to cefepime following oleic acid-induced acute lung injury. A modified bronchoalveolar lavage technique, based on equilibration of infused 99mTc-DTPA, was used to measure ELF volume. Cefepime was administered intravenously at steady plasma levels. Six serial bronchoalveolar lavages were performed 5 h after the beginning of infusion. ELF to plasma cefepime concentration ratios were 95 +/- 17 and 100 +/- 14.5% in normal and injured lung respectively. When urea was used as marker, cefepime concentration ratios were underestimated at 16.4 +/- 2.7 and 73.9 +/- 8.4% respectively. Cefepime blood/ airspace clearance increased from 3.8 +/- 0.7 micro x min(-1) in controls to 39.8 +/- 4.9 microL x min(-1) in acute lung injury. It was concluded that: 1) cefepime concentrations in epithelial lining fluid were in equilibrium with those in plasma in both normal and injured lung after 5 h at steady plasma concentrations; 2) epithelial lining fluid cefepime concentration by the urea method was much less underestimated in injured versus normal lung; and 3) acute lung injury induces a 10-fold elevation of cefepime blood/airspace clearance.