Calmodulin antagonists inhibit and phorbol esters enhance transferrin endocytosis and iron uptake by immature erythroid cells

Seven antagonists of the calcium-binding protein calmodulin were found to inhibit iron and transferrin uptake by reticulocytes. This inhibition could be completely accounted for by inhibition of the endocytosis and exocytosis of transferrin. When four of the antagonists were tested with the nucleated erythroid cells from the liver of the fetal rat, inhibition of iron uptake was also observed but at higher concentrations than required for the same degree of inhibition with reticulocytes. The tumor promoters phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDB) were shown to increase the rates of iron and transferrin uptake by reticulocytes and fetal liver erythroid cells by accelerating the rates of transferrin endocytosis and exocytosis. Since these substances are known to stimulate the calcium-activated enzyme protein kinase C while calmodulin antagonists are inhibitory, it is concluded that this enzyme plays an important role in the endocytosis and intracellular cycling of transferrin, and iron uptake by immature erythroid cells. However, the possibilities that calmodulin is also involved or that the inhibitory effects of the calmodulin antagonists are due to nonspecific actions on the cell membrane cannot be excluded.     

Extremely High Body Mass Index is not a Contraindication to Laparoscopic Gastric Bypass

Background: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is an effective operation for morbidly obese patients who have failed conservative weight loss treatments. It is currently indicated for patients with BMI >40 kg/m² or >35 with significant co-morbidities. Controversy exists whether there is an upper limit to BMI beyond which this operation should not be performed. Methods: Between April 1999 and February 2001, 82 patients (19 male, 63 female) underwent LRYGBP. Average age was 43.6, and average BMI was 56 kg/m². These patients were divided into those with BMI <60 and those with BMI ≥60 kg/m². Results:There were 61 patients with BMI <60 and 21 patients with BMI ≥60. The groups were similar in age, gender, distribution or incidence of co-morbid conditions (diabetes, coronary artery disease, hypertension, sleep apnea, asthma) between the groups. The BMI ≥60 group had a significantly longer length of stay (6.6 days vs 5.3 days, P <0.05), and only 1 patient (BMI 85) developed an anastomotic leak and died. 2 patients in this group (BMI 62 and 73) developed small bowel obstruction requiring lysis of adhesions. 1 patient in the BMI <60 group developed a gastrojejunal stricture requiring balloon dilatation. Conclusion: While patients with a BMI ≥60 are at higher risk for postoperative complications, they are also at higher risk from continued extreme obesity. In our series, 85% of these patients had an uneventful postoperative course and began shedding excess weight. BMI ≥60 should not be a contraindication for LRYGBP.     

Spatial learning and neurogenesis: Effects of cessation of wheel running and survival of novel neurons by engagement in cognitive tasks

Physical exercise stimulates cell proliferation in the adult dentate gyrus and facilitates acquisition and/or retention of hippocampal‐dependent tasks. It is established that regular physical exercise improves cognitive performance. However, it is unclear for how long these benefits last after its interruption. Independent groups of rats received both free access to either unlocked (EXE Treatment) or locked (No‐EXE Treatment) running wheels for 7 days, and daily injections of bromodeoxyuridine (BrdU) in the last 3 days. After a time delay period of either 1, 3, or 6 weeks without training, the animals were tested in the Morris water maze (MWM) either in a working memory task dependent on hippocampal function (MWM‐HD) or in a visible platform searching task, independent on hippocampal function (MWM‐NH). Data confirmed that exposure of rats to 7 days of spontaneous wheel running increases cell proliferation and neurogenesis. In contrast, neurogenesis was not accompanied by significant improvements of performance in the working memory version of the MWM. Longer time delays between the end of exercise and the beginning of cognitive training in the MWM resulted in lower cell survival; that is, the number of novel surviving mature neurons was decreased when this delay was 6 weeks as compared with when it was 1 week. In addition, data showed that while exposure to the MWM‐HD working memory task substantially increased survival of novel neurons, exposure to the MWM‐NH task did not, thus indicating that survival of novel dentate gyrus neurons depends on the engagement of this brain region in performance of cognitive tasks. © 2015 Wiley Periodicals, Inc.     

Total hip prosthesis CT with single-energy projection-based metallic artifact reduction: impact on the visualization of specific periprosthetic soft tissue structures

Objectives

To compare the image quality of CT with iterative reconstruction alone and in association with projection-based single-energy metal artifact reduction (SEMAR) for the visualization of specific periarticular soft tissue structures in patients with hip prostheses.

Methods

CT studies from 48 consecutive patients with a hip prosthesis (24 unilateral and 24 bilateral) were retrospectively reconstructed using two different methods: iterative reconstruction (IR) alone and IR associated with SEMAR. The influence of metallic artifacts on the identification of various periarticular structures was evaluated subjectively by two readers. The image quality was compared in patients with unilateral and bilateral prostheses.

Results

Visualization of periprosthetic soft tissue was significantly improved by the SEMAR algorithm (p?<?0.0001). When SEMAR was associated with IR, the gluteus minimus and medius tendons, obturator internus muscle, prostate/uterus and bladder could be seen with medium or high confidence. There were no significant differences in image quality between patients with unilateral or bilateral prosthesis when SEMAR was used (p?>?0.2). This algorithm increased the detection of periarticular masses by 30 %.

Conclusion

SEMAR significantly improves the image quality of periarticular soft-tissue structures in patients with hip prostheses.     

Influence of Calcium on Choline Measurements by 1H MR Spectroscopy of Thigh Muscles

Objective

To study the effects of calcium on the choline peak measurements with 1H MR spectroscopy.

Material and methods

The thigh muscles of two cadaveric specimens were prospectively evaluated on a 3 T MR unit before and after the injection of calcium carbonate (up to 0.4322 g). The choline peaks of 147 spectra from 10 different anatomic locations were quantitatively evaluated. The influence of the calcium concentration and its disposition with respect to the main magnetic field were considered. B₀ phase maps were used to evaluate field inhomogeneities.

Results

The presence of calcium led to a 43 % underestimation of the choline peak and the choline concentration (p?=?0.0002 and 0.0036). The mean choline concentrations before and after CaCO3 injection were 3.53?±?1.72 mmol/l and 1.58?±?0.63 mmol/l. The influence of calcium carbonate on the choline peak estimations was proportional to the calcium concentration. There was a significant position-dependent difference in the estimation of the choline peak amplitude (p?<?0.0154). Calcium injection led to a measurable increase in field inhomogeneities.

Conclusion

There was a significant underestimation of the choline peak amplitude and concentration in the presence of calcium, which might cause misinterpretations of MR spectra.

Key Points

? The presence of calcium led to significant underestimation of choline measurements. ? The influence of calcium is dependent on its concentration and distribution. ? Quantitative MR spectroscopy of calcified tumours should be interpreted with caution.     

Oral administration of antioxidants improves skin wound healing in diabetic mice

Oxidative stress aggravates several long‐term complications in diabetes mellitus. We evaluated the effectiveness of the oral administration of antioxidants (vitamins E and C, 40 and 100 mg/kg b.w., respectively) on skin wound healing acceleration in alloxan‐induced diabetic mice. Mice were wounded 30 days after the induction of diabetes. Antioxidants were effective in preventing oxidative stress, as assessed by TBARS. The enzymes catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were increased in diabetics on the 3rd day post‐wounding; catalase and glutathione peroxidase remained still augmented in diabetics after 14th day postwounding, and the treatment with vitamins restored their activities to control. After 3 days, diabetic mice showed lower infiltration of inflammatory cells (including CD11b⁺ and Ly6G⁺ cells) and reduced levels of KC, TNF‐α, IL‐1β, and IL‐12 p40 when compared with control mice. The treatment restored cytokine levels. After 14 days, diabetic mice showed late wound closure, persistent inflammation and delayed reepithelialization, accompanied by an increase in MIG⁺/CD206^? macrophages whereas CD206⁺/MIG^? macrophages were decreased. Cytokines IL‐12p40, TNF‐α, IL‐1β, and KC were increased and normal levels were restored after treatment with antioxidants. These results suggest that oxidative stress plays a major role in diabetic wound healing impairment and the oral administration of antioxidants improves healing by modulating inflammation and the antioxidant system with no effect on glycemia.