Effects of intermittent exposure to aflatoxin B1 on DNA and RNA adduct formation in rat liver: dose-response and temporal patterns.

We studied the effects of intermittent exposure to aflatoxin B1 (AFB1) on hepatic DNA and RNA adduct formation. Fisher-344 male rats were fed 0.01, 0.04, 0.4, or 1.6 ppm of AFB1 intermittently for 8, 12, 16, and 20 weeks, alternating with 4 weeks of dosing and 4 weeks of rest. Other groups of rats were fed 1.6 ppm of AFB1 continuously for 4, 8, 12, and 16 weeks. Control rats received AFB1-free NIH-31 meal diet. AFB1-DNA and -RNA adducts were measured by HPLC with fluorescence detection. The data are presented as total DNA or RNA adducts. The DNA and RNA adduct levels increased or decreased depending on the cycles of dosing and rest. Rats removed from treatment 1 month after 1 or 2 dosing cycles (8 and 16 weeks of intermittent exposure) showed approximately a twofold decrease in DNA adduct levels and a two- to elevenfold decrease in RNA adduct levels compared with rats euthanized immediately after the last dosing cycle (12 and 20 weeks of intermittent exposure). Our data indicate that DNA and RNA adducts increased linearly, from 0.01 ppm to 1.6 ppm of AFB1 after 12 and 20 weeks of intermittent treatment. A linear dose response was also apparent for DNA but not for RNA adducts after 8 and 16 weeks of treatment. As biomarkers of exposure, AFB1-RNA adducts were three to nine times more sensitive than AFB1-DNA adducts but showed greater variability. These results suggest that binding of AFB1 to hepatic DNA is a linear function of the dose, regardless of the way this is administered. The dose-response relationship for RNA adducts depends on the length of the no-dosing cycles and on the turnover rate of RNA.     

An animal component free medium that promotes the growth of various animal cell lines for the production of viral vaccines

IPT-AFM is a proprietary animal component free medium that was developed for rabies virus (strain LP 2061) production in Vero cells. In the present work, we demonstrated the versatility of this medium and its ability to sustain the growth of other cell lines and different virus strains. Here, three models were presented: Vero cells/rabies virus (strain LP 2061), MRC-5 cells/measles virus (strain AIK-C) and BHK-21 cells/rabies virus (strain PV-BHK21). The cell lines were first adapted to grow in IPT-AFM, by progressive reduction of the amount of serum in the culture medium. After their adaptation, BHK-21 cells grew in suspension by forming clumps, whereas MRC-5 cells remained adherent. Then, kinetics of cell growth were studied in agitated cultures for both cell lines. In addition, kinetics of virus replication were investigated.     

Outcomes and treatments of patients with immunoglobulin light chain amyloidosis who progress or relapse postautologous stem cell transplant

Immunoglobulin light chain (AL) Amyloidosis is a condition whereby misfolded proteins generated by plasma cells deposit in tissues causing organ dysfunction. Chemotherapy and autologous stem cell transplant when eligible are standard treatment options. Several studies report long‐term outcomes of patients post‐transplant. However, there is a paucity of literature describing outcomes of relapsed patients post‐transplant. We performed a retrospective study to assess outcomes and therapies employed upon relapse after transplant. Between 1996 and 2009, 410 patients received transplant at the Mayo Clinic as first‐line therapy. Of those patients, 42 (10%) died within 3 months of transplant, 64 (16%) died without documented relapse, 158 (38%) were alive without documented progression, and 146 (36%) had documented progression. Those 146 patients are the subject of our study, and their median time to hematologic relapse/progression was 23.6 months (95%CI 18.3, 26.3 months). Their median overall survival and 5‐yrs overall survival from post‐transplant relapse/progression was 51.7 months (95%CI 34.1–62.3) and 39%, respectively. The most common first regimen for treatment after relapse was lenalidomide or thalidomide. In conclusion, our study indicates that patients with AL amyloidosis fare well post‐transplant relapse/progression. Additionally, it provides a yardstick to design clinical trials to determine best treatment options.     

Infection-related ventilator-associated complications in ICU patients colonised with extended-spectrum β-lactamase-producing Enterobacteriaceae

Purpose

To investigate the clinical significance of infection-related ventilator-associated complications (IVAC) and their impact on carbapenem consumption in mechanically ventilated (MV) patients colonised with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLE).

Methods

Inception cohort study from the French prospective multicenter OUTCOMEREA database (17 ICUs, 1997–2015) including all ESBLE carriers (systematic rectal swabbing at admission then weekly and/or urinary or superficial surgical site colonisation) with MV duration?>?48 h and?≥?1 episode of IVAC after carriage documentation. All ICU-acquired infections were microbiologically documented.

Results

The 318 enrolled ESBLE carriers (median age 68 years; males 67%; medical admission 68%; imported carriage 53%) experienced a total of 576 IVAC comprising 361 episodes (63%) without documented infection, 124 (21%) related to infections other than ventilator-associated pneumonia (VAP), 73 (13%) related to non-ESBLE VAP and 18 (3%) related to ESBLE VAP. Overall, ESBLE infections accounted for only 43 episodes (7%). Carbapenem exposure within the preceding 3 days was the sole independent predictor of ESBLE infection as the causative event of IVAC, with a protective effect (adjusted odds ratio 0.2, 95% confidence interval 0.05–0.6; P?<?0.01). Carbapenems were initiated in 9% of IVAC without infection, 15% of IVAC related to non-VAP infections, 42% of IVAC related to non-ESBLE VAP, and 56% of IVAC related to ESBLE VAP (ESBLE VAP versus non-ESBLE VAP: P?=?0.43).

Conclusions

IVAC in ESBLE carriers mostly reflect noninfectious events but act as a strong driver of empirical carbapenem consumption. ESBLE infections are scarce yet hard to predict, strengthening the need for novel diagnostic approaches and carbapenem-sparing alternatives.

     

Hemolytic-uremic syndrome secondary to scorpion envenomation (apropos of 2 cases)

HUS was recently described following scorpion sting. We report 2 cases of HUS in the intensive care unit of a university hospital. Two children aged respectively 10 months and 1 year were admitted in the ICU after severe scorpion envenomation (with coma and pulmonary oedema) having required dobutamine and mechanical ventilation. Evolution was marked with acute anaemia without bleeding requiring blood transfusion, acute renal failure, low platelets and signs of haemolysis. Our experience and the previously reported case suggest that scorpion sting could be added to the list of causes of the HUS.     

Impact of sertraline on weight,waist circumference and glycemic control: A prospective clinical trial on depressive diabetic type 2 patients

Aim

Depression is prevalent in patients with type 2 diabetes. It may have a negative impact on the management of diabetes mellitus and could affect weight. The main aim of the investigation was to evaluate the effect of antidepressant treatment (sertraline) on anthropometric variables and glycemic control in depressed type 2 diabetic patients.