[Nanopsychiatry. The potential role of nanotechnologies in the future of psychiatry. A systematic review]. / La nanopsychiatrie. Le rôle potentiel des nanotechnologies dans l'avenir de la psychiatrie. Une revue systématique.

INTRODUCTION: Nanomedicine is defined as the area using nanotechnology's concepts for the benefit of human beings, their health and well being. The field of nanotechnology opened new unsuspected fields of research a few years ago. AIM OF THE STUDY: To provide an overview of nanotechnology application areas that could affect care for psychiatric illnesses. METHODS: We conducted a systematic review using the PRISMA criteria (preferred reporting items for systematic reviews and meta-analysis). Inclusion criteria were specified in advance: all studies describing the development of nanotechnology in psychiatry. The research paradigm was: "(nanotechnology OR nanoparticles OR nanomedicine) AND (central nervous system)" Articles were identified in three research bases, Medline (1966-present), Web of Science (1975-present) and Cochrane (all articles). The last search was carried out on April 2, 2012. Seventy-six items were included in this qualitative review. RESULTS: The main applications of nanotechnology in psychiatry are (i) pharmacology. There are two main difficulties in neuropharmacology. Drugs have to pass the blood brain barrier and then to be internalized by targeted cells. Nanoparticles could increase drugs' bioavailability and pharmacokinetics, especially improving safety and efficacy of psychotropic drugs. Liposomes, nanosomes, nanoparticle polymers, nanobubbles are some examples of this targeted drug delivery. Nanotechnologies could also add new pharmacological properties, like nanohells and dendrimers; (ii) living analysis. Nanotechnology provides technical assistance to in vivo imaging or metabolome analysis; (iii) central nervous system modeling. Research teams have modelized inorganic synapses and mimicked synaptic behavior, essential for further creation of artificial neural systems. Some nanoparticle assemblies present the same small world and free-scale network architecture as cortical neural networks. Nanotechnologies and quantum physics could be used to create models of artificial intelligence and mental illnesses. DISCUSSION: Even if nanotechnologies are promising, their safety is still tricky and this must be kept in mind. CONCLUSION: We are not about to see a concrete application of nanomedicine in daily psychiatric practice. However, it seems essential that psychiatrists do not forsake this area of research the perspectives of which could be decisive in the field of mental illness.

Influence of in vitro maturation of engineered cartilage on the outcome of osteochondral repair in a goat model.

This study was designed to determine if the maturation stage of engineered cartilage implanted in a goat model of cartilage injury influences the repair outcome. Goat engineered cartilage was generated from autologous chondrocytes cultured in hyaluronic acid scaffolds using 2 d, 2 weeks or 6 weeks of pre-culture and implanted above hydroxyapatite/hyaluronic acid sponges into osteochondral defects. Control defects were left untreated or treated with cell-free scaffolds. The quality of repair tissues was assessed 8 weeks or 8 months post implantation by histological staining, modified O'Driscoll scoring and biochemical analyses. Increasing pre-culture time resulted in progressive maturation of the grafts in vitro. After 8 weeks in vivo, the quality of the repair was not improved by any treatment. After 8 months, O'Driscoll histology scores indicated poor cartilage architecture for untreated (29.7 ± 1.6) and cell-free treated groups (24.3 ± 5.8). The histology score was improved when cellular grafts were implanted, with best scores observed for grafts pre-cultured for 2 weeks (16.3 ± 5.8). As compared to shorter pre-culture times, grafts cultured for 6 weeks (histology score: 22.3 ± 6.4) displayed highest type II/I collagen ratios but also inferior architecture of the surface and within the defect, as well as lower integration with native cartilage. Thus, pre-culture of engineered cartilage for 2 weeks achieved a suitable compromise between tissue maturity and structural/integrative properties of the repair tissue. The data demonstrate that the stage of development of engineered cartilage is an important parameter to be considered in designing cartilage repair strategies.

Are ankle chondrocytes from damaged fragments a suitable cell source for cartilage repair?

OBJECTIVE: To characterize the post-expansion cartilage-forming capacity of chondrocytes harvested from detached fragments of osteochondral lesions (OCLs) of ankle joints (Damaged Ankle Cartilage Fragments, DACF), with normal ankle cartilage (NAC) as control. DESIGN: DACF were obtained from six patients (mean age: 35 years) with symptomatic OCLs of the talus, while NAC were from 10 autopsies (mean age: 55 years). Isolated chondrocytes were expanded for two passages and then cultured in pellets for 14 days or onto HYAFF-11 meshes (FAB, Italy) for up to 28 days. Resulting tissues were assessed histologically, biochemically [glycosaminoglycan (GAG), DNA and type II collagen (CII)] and biomechanically. RESULTS: As compared to NAC, DACF contained significantly lower amounts of DNA (3.0-fold), GAG (5.3-fold) and CII (1.5-fold) and higher amounts of type I collagen (6.2-fold). Following 14 days of culture in pellets, DACF-chondrocytes generated tissues less intensely stained for Safranin-O and CII, with significantly lower GAG contents (2.8-fold). After 28 days of culture onto HYAFF((R))-11, tissues generated by DACF-chondrocytes were less intensely stained for Safranin-O and CII, contained significantly lower amounts of GAG (1.9-fold) and CII (1.4-fold) and had lower equilibrium (1.7-fold) and dynamic pulsatile modulus (3.3-fold) than NAC-chondrocytes. CONCLUSION: We demonstrated that DACF-chondrocytes have inferior cartilage-forming capacity as compared to NAC-chondrocytes, possibly resulting from environmental changes associated with trauma/disease. The study opens some reservations on the use of DACF-derived cells for the repair of ankle cartilage defects, especially in the context of tissue engineering-based approaches.

[Life-threatening postpartum hemorrhage and recombinant activated factor rFVIIa NovoSeven use]. / Hémorragie de la délivrance "menaçant la vie" et utilisation du facteur VII recombinant activé rFVIIa NovoSeven.

Postpartum haemorrhage remains a dangerous obstetrical complication, which is the main cause of maternal mortality in developing countries. The diagnosis must be immediate and its management is both medically and surgically in life-threatening haemorrhage. We present a case of a thirty-three-year-old woman who asked a pregnancy interruption for premature rupture of membranes at 21(th) gestational week for her second pregnancy; she underwent a caesarean section at term for her first pregnancy. She delivered vaginally and developed a postpartum haemorrhage with hemorrhagic shock which was resistant to medical, surgical and radiological management. We decided to use recombinant activated factor VII (rFVIIa, NovoSeven) as a final attempt to rescue the patient. During surgery, two intravenous bolus injections (60, 120 mug/kg) were successfully given with a control of bleeding and haemoglobin. The patient developed later a splenic thrombosis that can be related to either rFVIIa or to the hypovolemic shock or to the sepsis. Recombinant activated factor VII is an interesting and promising haemostatic agent in the management of life-threatening postpartum haemorrhage unresponsive to conventional treatment.

Cartilage tissue engineering by expanded goat articular chondrocytes.

In this study we investigated whether expanded goat chondrocytes have the capacity to generate cartilaginous tissues with biochemical and biomechanical properties improving with time in culture. Goat chondrocytes were expanded in monolayer with or without combinations of FGF-2, TGF-beta1, and PDGFbb, and the postexpansion chondrogenic capacity assessed in pellet cultures. Expanded chondrocytes were also cultured for up to 6 weeks in HYAFF-M nonwoven meshes or Polyactive foams, and the resulting cartilaginous tissues were assessed histologically, biochemically, and biomechanically. Supplementation of the expansion medium with FGF-2 increased the proliferation rate of goat chondrocytes and enhanced their postexpansion chondrogenic capacity. FGF-2-expanded chondrocytes seeded in HYAFF-M or Polyactive scaffolds formed cartilaginous tissues with wet weight, glycosaminoglycan, and collagen content, increasing from 2 days to 6 weeks culture (up to respectively 2-, 8-, and 41-fold). Equilibrium and dynamic stiffness measured in HYAFF M-based constructs also increased with time, up to, respectively, 1.3- and 16-fold. This study demonstrates the feasibility to engineer goat cartilaginous tissues at different stages of development by varying culture time, and thus opens the possibility to test the effect of maturation stage of engineered cartilage on the outcome of cartilage repair in orthotopic goat models.

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Molecular cloning of a hemopexin-like cDNA from rainbow trout liver.

Hemopexin is an abundant heme-binding serum protein synthesized in the liver and for which the sequence is determined only for mammals. Little is known about fish heme-binding proteins. We have cloned a rainbow trout complementary DNA that encodes a 445 amino acid polypeptide exhibiting an overall 30% homology with human hemopexin and 69% with the goldfish warm temperature acclimation-related 65-kDa protein. Structural homology, deduced from hydrophobic cluster analysis (HCA), was strong between the trout and human proteins since global HCA scores of 76% were obtained when the N- or C-terminal halves of the two proteins were compared. Moreover, several characteristics of hemopexin were found in the trout protein; finally, the trout hemopexin-like messenger RNA was specifically expressed in the liver. We conclude that the trout protein is a good candidate for a true fish hemopexin.

[Cesarean section for failed vacuum extraction: risk factors and maternal and neonatal outcomes]. / Césarienne pour échec d'extraction par ventouse obstétricale: facteurs de risque et conséquences maternelles et néonatales.

OBJECTIVE: To evaluate risk factors associated with failed attempts of vacuum extraction and their outcomes. PATIENTS AND METHODS: All trial vacuum extractions (metal Minicup) from 1992 to 2000 in Besançon University Hospital Center were retrospectively analysed, namely 2447 cases. Univariate and multivariate analyses of failed vacuum extraction risk factors and descriptive analyse of outcomes were performed. RESULTS: The rate of failed vacuum extractions was 3.47% (85/2447). A multivariate analysis showed the following independent risks factors in failed extraction: extraction above pelvic level + 2 (OR = 1.8; CI 95%: 1.1-3), newborn weight (OR = 2.9; CI 95%: 1.8-4.9), parity >2 (OR = 0.08; CI 95%: 0.01-0.6). In case of failed vacuum extraction, newborns had a significantly higher rate of Apgar score <7 at 1 min (P = 0.0002), but not at 5 min. These newborns were most regularly admitted in pediatric care units (P = 0.01). CONCLUSION: The failed trial attempt vacuum extraction rate stays low. These failed instrumental extractions are more common in an extraction above pelvic + 2, a high fetal weight and an arrest during the second stage of labor. There is an increased adverse neonatal outcome. Clinical fetal weight estimation and diagnosis of presentation level in mother pelvis must be performed before vacuum extraction.

[Lactate measurements and acid-base balance in cord blood]. / Lactates et équilibre acido-basique au sang du cordon.

OBJECTIVE: To compare two techniques of lactate measurements in cord blood: either by electrochemical strip method with Lactate Pro of KDK in the umbilical artery alone (series 1) or by enzymatic method with Rapid lab Analyzer of Bayer in the two vessels (series 2) with acid base balance being also determined. SUBJECTS AND METHODS: Series 1 included 353 neonates with a mean gestational age of 37 (+/- 3.6) weeks and series 2 included 410 newborns with a mean gestational age of 38 (+/- 3.1) weeks. RESULTS: Data was presented as mean and SD. In the first series mean umbilical artery lactate concentration was 3.71 (+/- 1.81) mmol/l. In the second series mean umbilical artery blood gas and lactate levels were as follows: pH = 7.25 (+/- 0.9), pCO2 = 6.55 (+/- 1.39) kPa; BD = 6.61 (+/- 3.33) mmol/l, lactate 3.92 (+/- 1.81) mmol/l. The 3rd percentile of pH was 7.05 whereas the 97th percentile of lactate was 7.54 mmol/l. There was a close correlation between lactate and pH, and lactate and BD. Lactate concentration was higher in case of instrumental delivery compared to spontaneous one: 4.65 versus 3.76 mmol/l (p = 0.0001, Student test). No perfect correlation was found between lactate level and neonatal outcome but there was not a significant number of neonates with immediate complication. CONCLUSION: Lactate measurements obtained with single use strip method are valuable and easy to perform.

Nanopsychiatry--the potential role of nanotechnologies in the future of psychiatry: a systematic review.

Nanomedicine is defined as the area using nanotechnology's concepts for the benefit of human beings' health and well being. In this article, we aimed to provide an overview of areas where nanotechnology is applied and how they could be extended to care for psychiatric illnesses. The main applications of nanotechnology in psychiatry are (i) pharmacology. There are two main difficulties in neuropharmacology: drugs have to pass the blood-brain barrier and then to be internalized by targeted cells. Nanoparticles could increase drugs bioavailability and pharmacokinetics, especially improving safety and efficacy of psychotropic drugs. Liposomes, nanosomes, nanoparticle polymers, nanobubbles are some examples of this targeted drug delivery. Nanotechnologies could also add new pharmacological properties, like nanoshells and dendrimers (ii) living analysis. Nanotechnology provides technical assistance to in vivo imaging or metabolome analysis (iii) central nervous system modeling. Research teams have succeeded to modelize inorganic synapses and mimick synaptic behavior, a step essential for further creation of artificial neural systems. Some nanoparticle assemblies present the same small worlds and free-scale networks architecture as cortical neural networks. Nanotechnologies and quantum physics could be used to create models of artificial intelligence and mental illnesses. We are not about to see a concrete application of nanomedicine in daily psychiatric practice. Even if nanotechnologies are promising, their safety is still inconsistent and this must be kept in mind. However, it seems essential that psychiatrists do not forsake this area of research the perspectives of which could be decisive in the field of mental illness.

[Bleeding secondary to vitamin K antagonist treatment: adaptation of the International Normalized Ratio (INR) determination during high hypertriglyceridemia]. / Accident hémorragique sous antagonistes de la vitamine K: adaptation de la détermination de l'International Normalized Ratio (INR) dans les hypertriglycéridémies majeures.

Vitamin K antagonists (VKA) are the first cause of iatrogenic mortality in France. Therefore, it is crucial to monitor these treatments with the International Normalized Ratio (INR) determination, which can be altered by several plasma elements. We report a patient who presented a serious bleeding event while under VKA treatment related to INR determination difficulties due to a high hypertriglyceridemia. We suggest some solutions (fasting and mechanic method in INR determination) in order to improve the control of the VKA treatment for patients with hypertriglyceridemia.

Engineered cartilage generated by nasal chondrocytes is responsive to physical forces resembling joint loading.

OBJECTIVE: To determine whether engineered cartilage generated by nasal chondrocytes (ECN) is responsive to different regimens of loading associated with joint kinematics and previously shown to be stimulatory of engineered cartilage generated by articular chondrocytes (ECA). METHODS: Human nasal and articular chondrocytes, harvested from 5 individuals, were expanded and cultured for 2 weeks into porous polymeric scaffolds. The resulting ECN and ECA were then maintained under static conditions or exposed to the following loading regimens: regimen 1, single application of cyclic deformation for 30 minutes; regimen 2, intermittent application of cyclic deformation for a total of 10 days, followed by static culture for 2 weeks; regimen 3, application of surface motion for a total of 10 days. RESULTS: Prior to loading, ECN constructs contained significantly higher amounts of glycosaminoglycan (GAG) and type II collagen compared with ECA constructs. ECN responded to regimen 1 by increasing collagen and proteoglycan synthesis, to regimen 2 by increasing the accumulation of GAG and type II collagen as well as the dynamic modulus, and to regimen 3 by increasing the expression of superficial zone protein, at the messenger RNA level and the protein level, as well as the release of hyaluronan. ECA constructs were overall less responsive to all loading regimens, likely due to the lower extracellular matrix content. CONCLUSION: Human ECN is responsive to physical forces resembling joint loading and can up-regulate molecules typically involved in joint lubrication. These findings should prompt future in vivo studies exploring the possibility of using nasal chondrocytes as a cell source for articular cartilage repair.

Crossed retroperitoneal approach to the internal iliac artery: a preliminary anatomical study.

The internal iliac arteries (IIA), and especially the distal segment, course very deep in the pelvis and are generally difficult to access surgically. The recent development of simple and reliable methods to investigate proximal ischemia of the lower extremities has led to discovery of more candidates for elective revascularization of the IAA. The classic approaches to the IAA, i.e., the transperitoneal and homolateral retroperitoneal routs have certain disadvantages. We present a new crossed retroperitoneal approach to the IAA and the results of such method in six cadavers. In all six cases, the entire IAA could be exposed without any particular problems. This novel approach to the IAA seems to be both simple and reproducible.

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No complement receptor 1 stumps on podocytes in human glomerulopathies.

BACKGROUND: Type one complement receptor (CR1) is the only physiological inhibitor of complement on podocytes. CR1 is lost in different glomerulopathies, in particular in lupus nephritis, in which it has been suggested that CR1 is removed by proteolysis from the cell membrane. METHODS: To define whether proteolytic cleavage of CR1 on podocytes is a general phenomenon, we analyzed the expression of CR1 in different glomerulopathies using a monoclonal antibody against epitopes present on the extracellular portion of the molecule and a polyclonal antibody directed at the intracellular tail of CR1. The two antibodies were applied on sequential serial histologic sections of renal biopsy. RESULTS: In normal glomeruli, the two antibodies provided similar results, that is, strong staining of podocytes, and both were shown to recognize specifically CR1. Decreased expression of the extracellular portion of CR1 was observed in lupus nephritis (8/8), focal and segmental glomerulosclerosis (FSGS; 7/7), IgA nephritis (6/6), membranous glomerulonephritis (3/3), and minimal change disease (3/3). In each case, the decreased expression was accompanied by a simultaneous decrease of the expression of the intracellular tail of CR1 (Spearman's correlation coefficient rs = 0.951, P < 0.001). This observation was confirmed by analyzing focal glomerular lesions on sequential serial sections. CONCLUSION: These data indicate that there are no CR1 stumps on podocytes, even in lupus nephritis, and suggest that the CR1 loss on podocytes is not due to consumption but to decreased synthesis. A loss of CR1 synthesis might render podocytes highly sensitive to complement attack.