Vécus psychologiques des démarches d'assistance médicale à la procréation

Assisted Reproductive Technologies (ART) come along with important emotional and psychological burden, as well as the physical constraints, for both the woman and her partner. Couples entering ART programs are usually infertile ones, but some specific settings, like serodiscordant couples where the male partner is HIV positive, involving fertile couples. These couples are usually well-adjusted and motivated ones. During the treatments, waiting for the outcome, and the unsuccessful cycles are among the most stressfull experiences. Common reactions are stress, anxiety and depression, but for some couples, the difficulties are so great that they discontinue the program after only one attempt. When parents, the couples usually experience good parenting competencies, and the “precious” children, despite a greater genetic risk, usually have a normal development, but some specific psychological difficulties may arise, that may request a specific help.     

CD1 assembly and the formation of CD1-antigen complexes

The CD1 antigen presentation system presents lipid antigens to effector T cells, which have diverse roles in antimicrobial responses, antitumor immunity and in regulating the balance between tolerance and autoimmunity. The trafficking of CD1 molecules and lipid antigens facilitates their intersection and binding in specific intracellular compartments. Recent studies have now identified unexpected accessory molecules that are critical to CD1 assembly and lipid loading. The atomic structures of CD1-antigen complexes have defined both the orientation of polar headgroups between the alpha1 and alpha2 helices of CD1 and the manner in which distinct CD1 isoforms bind a range of lipids that have different lengths and numbers of hydrocarbon chains.     

Comparison of action of the anti-neoplastic drug lonidamine on drug-sensitive and drug-resistant human breast cancer cells:31 P and 13C nuclear magnetic resonance studies

Lonidamine (LND) is a relatively new anti-cancer drug,and several clinical trials have indicated that it may be effectivein combinations with other therapeutic modalities. LND isclassified within the metabolic inhibitor agents. Multidrugresistance (MDR) phenomenon is often associated with increasedenergy requirements, and enhanced glycolysis rate. These studieswere performed to delineate the mechanism of action of LNDon MDR human breast cancer cells, and to investigate whetherLND as a single agent, or in combination with anotheranti-metabolism drug, 2-deoxyglucose (2-DG), may be usefulagainst MDR tumors. The effects of LND on intact perfuseddrug-sensitive (WT) and 33-fold resistant to Adriamycin(Adr) MCF-7 cells, embedded in alginate micro capsules, were continuouslymonitored by ³¹P and ¹³C nuclearmagnetic resonance (NMR) spectroscopy. ³¹PNMR studies showed that LND induced intracellular acidificationand depletion of NTP in both WT and Adr cells. However, pH and NTPlevels decreased less in the Adr cells than in the WT cells(p < 0.05 for both parameters). ¹³CNMR demonstrated that LND inhibited lactate transport,and lactate signals were elevated in both cell lines. However, theintracellular lactate levels increased to a greater extentin the WT than in the Adr cells (p < 0.05).There were major differences in the effects of LND onmetabolism between sensitive and resistant cells.While LND enhanced glucose uptake in the WT cells, and itsadministration was followed by continuous increase oflactate signal, both processes were not affected by LNDin the Adr cells. 2-DG is a glucose analogue that inhibitsboth cellular uptake and utilization of glucose, leading to cell starvation. Combined treatment with LND and2-DG yielded at best additive, but not synergistic,cellular toxicity, and the metabolic effects of LNDwere attenuated by 2-DG. These results showed that the principalmechanism of action of LND is inhibition of lactate transportleading to intracellular lactate accumulation and acidificationin both WT and Adr cells. The Adr cells were only 2-fold resistantto LND (compared to the WT cells), and since cellular uptakeof alkaloid chemotherapy is improved in acidic environment,LND may have a role in the treatment protocols of MDR tumors,especially when given as the initial means for inductionof intracellular acidification.     

Chronic Pain and Premature Aging – The Moderating Role of Physical Exercise

Chronic pain induces a multitude of harmful effects; recently it has been suggested that chronic pain is also associated with premature aging, manifested in shortened telomere length (TL). However, evidence for this hypothesis is scarce and inconsistent. The aim was twofold: 1) Investigate whether chronic pain is associated with premature aging, and 2) Determine whether physical exercise (PE) moderates this association if it exists. Participants were 116 male subjects, with (n = 67) and without chronic pain (n = 49). Blood samples for TL analysis were collected and participants were interviewed and completed questionnaires. As a part of the cohort, we included people with physical disability; this variable was controlled in the analysis. The TL of individuals with chronic pain was significantly shorter than that of pain-free individuals. Regression analysis revealed a significant moderating effect of PE on chronic pain and TL, above and beyond the effects of disability, age, and weight. Whereas chronic pain was associated with shorter telomeres in participants who did not exercise, this association was nonsignificant among participants who did exercise. The results suggest that chronic pain is associated with premature ageing; however, PE may mitigate this association and may protect individuals against the harmful effects of chronic pain.PerspectiveThe study suggests that it is important to monitor signs of premature ageing among chronic pain patients as they are at risk. However, chronic pain patients may benefit from regular PE in this respect as it may moderate premature ageing.     

Intracellular labile iron pools as direct targets of iron chelators: a fluorescence study of chelator action in living cells

The primary targets of iron chelators used for treating transfusional iron overload are prevention of iron ingress into tissues and its intracellular scavenging. The present study was aimed at elucidating the capacity of clinically important iron chelators such as deferiprone (DFP), desferrioxamine, and ICL670 to (a) gain direct access to intracellular iron pools of key cells of iron accumulation (macrophages, hepatocytes, and cardiomyocyte cell lines); (b) chelate the labile iron present in discrete cell compartments/organelles; and (c) prevent labile iron involvement in the generation of reactive oxidant species. Chelation of cytosolic and organellar cell iron was visualized dynamically and quantitatively in living cells by fluorescence microscopic imaging of fluorescent metallosensors (used as iron-quenched complexes of calceins) targeted to either cytosol, endosome-lysosomes, or mitochondria. The rate and extent of fluorescence recovery provided an in situ measure of the accessibility of chelators to particular cell sites/organelles. Complementary, fluorogenic redox probes associated with cell compartments enabled identification of chelator-sensitive, localized reactive oxidant production. Our studies indicate that chelation by desferrioxamine is slow and is enhanced in cells with relatively high endocytic activities, while ICL670 and DFP readily enter most cells and efficiently reach the major intracellular sites of iron accumulation.     

Initial exposed phosphatidylserine levels correlate with cellular response to cytotoxic drugs

Phosphatidylserine's (PS) membranal distribution is associated with an expanding variety of biological processes. We studied the relevance of preliminarily exposed membranal PS levels to cellular effects of cytotoxic agents. PBL of normal controls (n = 18) and patients with doxorubicin-treated breast carcinoma (n = 27) or 5'-fluorouracil-treated colorectal cancer (n = 32) were assayed before and after drug infusion. Membranal expression levels of PS, adhesion molecules (CD18, CD11a-c, CD63) and Fas-R of leukocyte subtypes were assessed by flow cytometer. Statistical analysis was implemented. Our results demonstrate external expression of PS on all leukocyte subpopulations despite non-apoptotic light scatter characteristics. Several distinct features were observed of which the more prominent were: leukocyte subtypes each display characteristic PS levels; cancer patients' PBL display higher preliminary PS levels than normal controls in all cell groups; and existence of negative correlations between initial membranal PS levels and drug-induced changes in its expression. Our findings underscore the complex involvement of PS in PBL apoptosis and possibly drug resistance.     

Primary angioplasty with routine stenting compared with thrombolytic therapy in elderly patients with acute myocardial infarction

Background

Prior studies have yielded conflicting data on the advantage of primary angioplasty compared with thrombolysis in elderly patients with acute myocardial infarction (AMI). These studies, however, were performed before the contemporary widespread use of intracoronary stents and glycoprotien IIb/IIIa antagonists.

Methods

We prospectively compared the outcome of 130 consecutive elderly patients (aged ≥70 years) with ST-elevation AMI who were admitted to 2 similar neighboring medical centers. Patients were assigned to receive either thrombolytic therapy with accelerated tissue-type plasminogen activator (center I) or primary angioplasty with routine stenting (center II).

Results

Of the patients assigned to receive primary angioplasty, 91% underwent stenting. At 6 months, patients treated with primary angioplasty, compared with those treated with thrombolytic therapy, had a lower incidence of reinfarction (2% vs 14%, P = .053) and revascularization for recurrent ischemia (9% vs 61%, P < .001) and a significant reduction in the prespecified combined end point of death, reinfarction, or revascularization for recurrent ischemia (29% vs 93%, P < .01). Primary angioplasty remained an independent predictor of the triple combined end point after controlling for potential covariables (relative risk 0.63, 95% CI 0.38-0.84). Major bleeding complications were also significantly reduced in the primary angioplasty group (0% vs 17%, P = .03).

Conclusions

Compared with thrombolysis, primary angioplasty with routine stenting in elderly patients with AMI is associated with better clinical outcomes and a lower risk of bleeding complications.     

Vascular complications in steroid treated patients undergoing transfemoral aortic valve implantation

• Steroids if taken chronically or periprocedurally contribute to delayed wound healing and decreased vascular patency
• Access site complications after diagnostic interventional procedures carry significant morbidity, increased cost, and prolonged hospital stay
• TAVI offers high risk surgical candidates with severe aortic stenosis a significant survival advantage

     

Transfusion-Related Acute Lung Injury

Transfusion-related acute lung injury (TRALI) is related to the transfusion of blood components. Typically, it is a clinical syndrome, characterized by the sudden onset of dyspnea, hypoxemia and bilateral non-cardiogenic pulmonary edema. A 83-year-old female patient with a history of AML developed TRALI after receiving 6 units of platelets. TRALI symptoms was started 10 min later the transfusion. AML is a risky group for TRALI. While giving transfusion to the risky groups of TRALI one must be more careful. The mortality rate caused by TRALI will decrease if the patient who is thought to have TRALI or who has bilateral pulmonary edema without any other reason showing the existance of TRALI is given ventilatory support at the right time.