Thyrotropin activates guanosine 5'-diphosphate/guanosine 5'-triphosphate exchange on the rate-limiting endocytic catalyst, Rab5a, in human thyrocytes in vivo and in vitro

CONTEXT: We have previously reported that the TSH receptor/cAMP cascade enhances the coordinate expression of the rate-limiting endocytic catalysts, Rab5a and Rab7, which respectively promote thyroglobulin (Tg) internalization and transfer to lysosomes, thereby accelerating thyroid hormone secretion. OBJECTIVE: We address whether TSH further controls Rab5a activity by promoting its GTP-bound state. DESIGN: We compared Rab5a activation in seven pairs of hyperactive and corresponding quiescent thyroid tissues; TSH effect was reproduced on polarized cultures of normal human thyrocytes. PATIENTS: We studied seven euthyroid patients bearing hyperactive autonomous adenomas; normal thyroid tissue for culture. MAIN OUTCOME MEASUREMENTS: Rab5a GDP/GTP exchange factor activity [Rab5a-guanine nucleotide exchange factor (GEF)], expression of Rabex-5 (a Rab5a-GEF), and function of thyrocytes in vitro were the main outcome measures. RESULTS: In autonomous adenomas, constitutive activation increased both total activity and sedimentability (membrane recruitment) of Rab5a-GEF, compared with perinodular tissues. Increased Rab5a-GEF activity correlated with increased expression of Rabex-5 and Rab5a, as well as with Tg store depletion. In polarized human thyrocyte monolayers, TSH did not affect total Rab5a-GEF activity after 2 h but promoted its membrane recruitment; after 4 d, TSH increased both Rab5a-GEF activity and Rabex-5 expression and recruitment onto membranes where Rabex-5 coimmunoprecipitated with Rabaptin-5 and Rab5a. Sedimentable Rab5a-GEF perfectly correlated with apical endocytosis and lysosomal transfer of 125I-Tg, and with basolateral secretion of 125I-derived hormones. CONCLUSION: This study provides the first clinical and experimental evidence that regulation of the activity of a rate-limiting endocytic catalyst finely tunes a tightly controlled cellular function that ultimately governs whole body metabolism.     

An update on anemia in less developed countries

The highest prevalence of anemia exists in the developing world where its causes are multi-factorial. Anemia is responsible for significant morbidity and mortality, particularly in less developed countries (LDCs). Understanding causes of anemia and potential mechanisms are crucial to our ability to intervene to reduce this burden. In the past decade, our understanding of the etiology and mechanisms of anemia in LDCs has advanced significantly. This review will focus on recent advances in our understanding of the burden of anemia in specific sub-groups, the causes and mechanisms of anemia, and consequences of anemia for the human host.     

Assessment of acute ankle sprain with os subfibularein children

Children commonly present with acute inversion injuries of the ankle. Radiographs occasionally show small fragments under the tip of the lateral malleolus. The purpose of our study was to clarify their origin. A prospective standardized clinical examination and a magnetic resonance imaging were carried out. Among the 116 included patients, seven of them showed an os subfibulare. They presented more pains on the lateral ankle area than the other children. We found also more injuries on the anterior talofibular ligament. The os subfibulare could be secondary to an accessory ossification but the lateral area of the ankle would be likely to be injured.     

Prevalence of compulsive buying among customers of a Parisian general store

Compulsive buying is defined by the presence of repetitive impulsive and excessive buying, leading to personal and family distress. The objective of this study is to assess the prevalence of compulsive buying among "normal consumers" and to describe the specificities in the buying style of compulsive buyers. We tried to answer several questions. (1) Does compulsive buying occur more often during sales or periods of sales campaigns? (2) Is compulsive buying more impulsive and unplanned than normal buying? (3) Are compulsive buyers more "affectively" involved in their purchases (preference for specific brands they have a narcissistic relationship with, tendency to consider purchases as exceptional special occasions)? (4)Do women who buy compulsively use shopping Web sites and the Internet in general more than controls? We interviewed 200 women successively entering Les Galeries Lafayette, a famous Parisian department store. We diagnosed compulsive buying with standardized criteria and a specific rating scale. All subjects answered an additional questionnaire assessing their buying behavior. We also rated their duration of connection to the Web, the number of e-mails sent and received, and the time spent speaking on a cellular phone. Prevalence of compulsive buying was 32.5%. The proportion of married women was lower among compulsive buyers (66%) than in controls (85%). Compulsive buyers do not seek sales more than controls. Their decision to buy is more often made during their stay in the shop (48% vs 24%, chi(2) = 117, P < .001). Women buying compulsively consider more often their purchases as opportunities not to be passed by (33.7% vs 23.1%, P = .006). They have a higher tendency to use items less than expected (23.4% vs 14.4% in the control group, P < .001). They more often make purchases to impress others (6.5% vs 2.5%, P = .04) and consider more often their purchases as personally gratifying (44% vs 23%, P < .001). Their connections to online shopping sites are longer and more frequent. They spend significantly more time than controls speaking on their cellular phones.     

A pilot randomized study comparing high and low volume hemofiltration on vasopressor use in septic shock

OBJECTIVE: High volume hemofiltration (HVHF) has shown potential benefits in septic animals and a few reports suggested a hemodynamic improvement in humans. However, randomized studies are still lacking. Our goal was to evaluate the hemodynamic effects of HVHF in septic shock patients with acute renal failure (ARF). DESIGN AND SETTING: Prospective randomized study in an intensive care unit (ICU). PATIENTS: Twenty patients with septic shock and ARF. INTERVENTIONS: Patients were randomized to either high volume hemofiltration [HVHF 65 ml/(kg h)] or low volume hemofiltration [LVHF 35 ml/(kg h). Vasopressor dose was adjusted to reach a mean arterial pressure (MAP) > 65 mmHg. MEASUREMENTS AND RESULTS: We performed six hourly measurements of MAP, norepinephrine dose, PaO(2)/FiO(2) and lactate, and four daily urine output and logistic organ dysfunction (LOD) score. Baseline characteristics of the two groups were comparable on randomization. Mean norepinephrine dose decreased more rapidly after 24 h of HVHF treatment compared to LVHF treatment (P = 0.004) whereas lactate and PaO(2)/FiO(2) did not differ between the two treatment groups. During the 4-day follow-up, urine output was slightly increased in the HVHF group (P = 0.059) but the LOD score evolution was not different. Duration of mechanical ventilation, renal replacement therapy and ICU length of stay were also comparable. Survival on day 28 was not affected. CONCLUSION: HVHF decreased vasopressor requirement and tended to increase urine output in septic shock patients with renal failure. However, a larger trial is required to confirm our results and perhaps to show a benefit in survival.