Benznidazole vs benznidazole in multilamellar liposomes: how different they interact with blood components?

In spite of its widespread use, benznidazole's (BNZ) toxicity and low efficacy remains as major drawbacks that impair successful treatments against Chagas disease. Previously, attempting to increase the selectivity and reduce its toxicity on infected tissues, multilamellar liposomes (MLV) composed of hydrogenated soybean phosphatidylcholine (HSPC): distearoyl-phosphatidylglycerol (DSPG): cholesterol (CHOL) 2:1:2 mol:mol loaded with BNZ (MLV-BNZ) were designed. In this work we compared different properties of MLV-BNZ with those of BNZ. Opposite to other hydrophobic drugs, the results indicated that slight changes of BNZ×s association degree to proteins and lipoproteins should not modify the percentage of unbound drug available to exert pharmacological action. On the other hand, when loaded in MLV, BNZ reduced its association to plasma proteins in 45% and became refractory to the sinking effect of blood, dropping 4.5 folds. Additionally, when loaded in MLV, BNZ had higher volume distribution (160 ± 20 vs 102 ± 15 ml/kg) and total clearance (35.23 ± 2.3 vs 21.9 ± 1.4 ml/h.kg), and lower concentration-time curve (7.23 ± 0.2 vs 9.16 ± 0.5 µg.h/ml) than BNZ. Hence, these studies showed that for MLV-BNZ, the amount of BNZ can be substantially increased, from 25 to 70%, being this formulation more rapidly cleared from circulation than free drug; also due to the lower interaction with blood components, lower side effects can be expected.

Paralysies laryngées unilatérales [Unilateral laryngeal paralysis].

Investigations, diagnosis and treatment of laryngeal paralysis depend upon history taking and examination of phonation, swallowing and of the pharyngo-larynx. In unilateral paralysis, the main symptom is dysphonia. Dysphagia lasting more than 10 days may indicate a proximal vagus nerve lesion. Voice and swallowing therapy may be undertaken. If this remains insufficient after one month, a temporary or definitive vocal fold medialisation may be considered. Paralysis is considered to be definitive if lasting for more than 12 months. A minimal of one-year follow-up is indicated in case of idiopathic paralysis.

Recurrence of keratoconus characteristics: a clinical and histologic follow-up analysis of donor grafts.

PURPOSE: To report on clinical corneal topography, histopathologic analysis, and fine structure findings in failed grafts after penetrating keratoplasty (PK) for keratoconus (KC). DESIGN: Retrospective, consecutive, interventional case series with histologic and clinical correlation. PARTICIPANTS: Twelve corneal buttons were obtained from consecutive patients undergoing repeated PK 10 to 28 years after the initial PK for KC. The indication for regrafting was endothelial deficiency in seven cases, irreversible immune graft rejection in two cases, and corneal ectasia in three cases. METHODS: Removed corneal buttons were examined by light and transmission electron microscopy. A potential correlation between the clinical and videokeratoscopic findings and the microscopic structural observations was analyzed. RESULTS: Preoperative simulated keratometry measured by TMS-1 (Tomey, New York, NY) or EyeSys CAS (EyeSys Technology, Houston, TX) ranged from 49.8 to 66.1 diopters. A pattern compatible with KC characteristics was observed in all cases. Fine structure analysis revealed Bowman's layer disruption or folds and stromal deposits in all corneal buttons. However, central corneal thinning was not present in any of the removed buttons. CONCLUSIONS: Structure changes compatible with the diagnosis of KC were observed in all donor buttons many years after PK on KC recipients. Recurrence of the KC characteristics may result from graft repopulation by recipients' keratocytes, aging of the grafted tissue, or both.

Keratouveitis caused by sap of Euphorbia myrsinites plant.

BACKGROUND: Euphorbia plants grow in many gardens. Their milky latex is, however, a strong irritant which may induce various ocular lesions from keratoconjunctivitis to severe uveitis. HISTORY AND SIGNS: A 86-year-old woman developed a unilateral severe anterior chamber inflammation associated with descemtic folds after direct contact with sap of Euphorbia. Visual acuity was limited to counting fingers. Her eye was operated from filtering surgery ten years previously. The patient was closely followed to rule out the diagnosis of bacterial endophthalmitis. THERAPY AND OUTCOME: Symptoms progressively resolved after topical administration of 3 mg/mL ofloxacine and 1 % prednisolone acetate. CONCLUSIONS: Euphorbia sap toxicity may take different forms from keratoconjunctivitis to severe uveitis. Euphorbia sap-induced uveitis should be kept in mind when the patient has seen in contact with freshly cut plants.

Sib-sib communication and the risk of prey theft in the barn owl Tyto alba

Conflicts among siblings are widespread and their resolution involves complex physical and communication tools. Observations in the barn owl Tyto alba showed that siblings vocally communicate in the absence of parents to negotiate priority of access to the impending food resources that parents will bring. In the present paper, we hypothesize and provide correlative evidence that after a parent brought a food item to their progeny, sibling competition involves vocal sib-sib communication. A food item takes a long time to be entirely consumed, and hence siblings continue to compete over prey monopolization even after parents gave a food item to a single offspring. When physical competition is pronounced and thereby the risk of prey theft is high, the individual that received a prey item consumes it in a concealed place. Concomitantly, nestlings vocalize intensely probably to indicate their motivation to siblings to not share their food item, since this vocal behaviour was particularly frequent in younger individuals for which the risk of being robbed is higher than in their older siblings. Furthermore, nestlings consumed more rapidly a food item when their siblings vocalized intensely presumably because the intensity of siblings' vocalizations is associated with a risk of prey theft. Our correlative study suggests that sibling competition favoured the evolution of sib-sib communication under a wide range of situations.

Ghrelin-induced orexigenic effect in rats depends on the metabolic status and is counteracted by peripheral CB1 receptor antagonism.

Ghrelin is an endogenous regulator of energy homeostasis synthesized by the stomach to stimulate appetite and positive energy balance. Similarly, the endocannabinoid system is part of our internal machinery controlling food intake and energy expenditure. Both peripheral and central mechanisms regulate CB1-mediated control of food intake and a functional relationship between hypothalamic ghrelin and cannabinoid CB1 receptor has been proposed. First of all, we investigated brain ghrelin actions on food intake in rats with different metabolic status (negative or equilibrate energy balance). Secondly, we tested a sub-anxiogenic ultra-low dose of the CB1 antagonist SR141716A (Rimonabant) and the peripheral-acting CB1 antagonist LH-21 on ghrelin orexigenic actions. We found that: 1) central administration of ghrelin promotes food intake in free feeding animals but not in 24 h food-deprived or chronically food-restricted animals; 2) an ultra-low dose of SR141716A (a subthreshold dose 75 folds lower than the EC50 for induction of anxiety) completely counteracts the orexigenic actions of central ghrelin in free feeding animals; 3) the peripheral-restricted CB1 antagonist LH-21 blocks ghrelin-induced hyperphagia in free feeding animals. Our study highlights the importance of the animaĺs metabolic status for the effectiveness of ghrelin in promoting feeding, and suggests that the peripheral endocannabinoid system may interact with ghrelińs signal in the control of food intake under equilibrate energy balance conditions.

Resuscitated sudden cardiac death caused by left main coronary artery compression by an aneurysm of the sinus of Valsalva.

A 49-year-old woman, without known cardiovascular risk factors. Hoarseness of voice caused by a paralysis of left vocal cord. She was admitted to hospital because of acute coronary syndrome, associated to resuscitated cardiac arrest (asystolia documented) without later neurology sequels. Physical examination was anodyne. Echocardiographic study demonstrated a compatible image with a large left sinus of Valsalva aneurysm (SVA) (Panel A) and mild aortic regurgitation. Cardiac catheterization confirmed the presence of left SVA (Panel B) that produced extrinsic compression of the left main coronary artery (Panels C and D). Repair surgery was made by means of closing the aneurysmal orifice with a patch of dacron. Intra-operatory echocardiographic control study found severe aortic regurgitation, so valvular replacement with 19 mm mechanical prosthesis and extension of the valve annulus with patch of dacron was performed, associated with bypass with safena vein graft to left coronary artery. SVA is a very infrequent cardiac anomaly, generally with silent clinical course until it ruptures. Myocardial ischaemia caused by coronary artery compression is unusual. We described the case of a patient diagnosed of left SVA, whose initial clinical manifestation was the appearance of resuscitated sudden cardiac death in the context of an acute coronary syndrome.

A functional and structural study of the major metalloprotease secreted by the pathogenic fungus Aspergillus fumigatus.

Fungalysins are secreted fungal peptidases with the ability to degrade the extracellular matrix proteins elastin and collagen and are thought to act as virulence factors in diseases caused by fungi. Fungalysins constitute a unique family among zinc-dependent peptidases that bears low sequence similarity to known bacterial peptidases of the thermolysin family. The crystal structure of the archetype of the fungalysin family, Aspergillus fumigatus metalloprotease (AfuMep), has been obtained for the first time. The 1.8 Å resolution structure of AfuMep corresponds to that of an autoproteolyzed proenzyme with separate polypeptide chains corresponding to the N-terminal prodomain in a binary complex with the C-terminal zinc-bound catalytic domain. The prodomain consists of a tandem of cystatin-like folds whose C-terminal end is buried into the active-site cleft of the catalytic domain. The catalytic domain harbouring the key catalytic zinc ion and its ligands, two histidines and one glutamic acid, undergoes a conspicuous rearrangement of its N-terminal end during maturation. One key positively charged amino-acid residue and the C-terminal disulfide bridge appear to contribute to its structural-functional properties. Thus, structural, biophysical and biochemical analysis were combined to provide a deeper comprehension of the underlying properties of A. fumigatus fungalysin, serving as a framework for the as yet poorly known metallopeptidases from pathogenic fungi.

An individualized approach to abdominoplasty in the presence of bilateral subcostal scars after open gastric bypass.

BACKGROUND: Patients requiring surgical skin excision after massive weight loss are challenging and require an individualized approach. The characteristic abdominal deformity includes a draping apron of panniculus, occasionally associated with previous transverse surgical scars from open gastric bypass surgery in the upper abdomen, which compromise blood supply of the abdominal skin. METHODS: We propose four different surgical techniques for safe abdominal body contouring in the presence of such scars: (1) a limited abdominoplasty of the lower abdomen is performed, and then contouring is completed by a reversed abdominoplasty with scar positioning in the submammary folds; (2) a one-stage procedure characterized by skin resection in the upper and lower abdomen, in which blood supply of the skin island between the submammary and suprapubic incisions is ensured by periumbilical perforators; (3) a perforator-sparing abdominoplasty with selective dissection of periumbilical abdominal wall perforators to secure flap blood supply and allow complete flap undermining up to the xyphoid process; (4) for patients with extensive excess skin, a modified Fleur-de-Lys abdominoplasty performed in such a way that the old transverse scar is transformed into a vertical scar. RESULTS: The treatment of four exemplary patients is described. All techniques yielded good esthetic and functional results through preservation of abdominal blood supply. CONCLUSION: Through an individualized approach, adequate abdominal body contouring can be performed safely, even in the presence of transverse surgical scars in the upper abdomen.

Structural and metamorphic evolution of the northern Himachal Himalaya, NW India - (Spiti-eastern Lahul-Parvati valley traverse)

The Himalayan orogen is the result of the collision between the Indian and Asian continents that began 55-50 Ma ago, causing intracontinental thrusting and nappe formation. Detailed mapping as well as structural and microfabric analyses on a traverse from the Tethyan Himalaya southwestward through the High Himalayan Crystalline and the Main Central Thrust zone (MCT zone) to the Lesser Himalayan Sequence in the Spiti-eastern Lahul-Parvati valley area reveal eight main phases of deformation, a series of late stage phases and five stages of metamorphic crystallization. This sequence of events is integrated into a reconstruction of the tectonometamorphic evolution of the Himalayan orogen in northern Himachal Pradesh. The oldest phase D-1 is preserved as relies in the High Himalayan Crystalline. Its deformational conditions are poorly known, but the metamorphic evolution is well documented by a prograde metamorphism reaching peak conditions within the upper amphibolite facies. This indicates that D-1 was an important tectonometamorphic event including considerable crustal thickening. The structural, metamorphic and sedimentary record suggest that D-1 most probably represents an early stage of continental collision. The first event clearly attributed to the collision between India and Asia is documented by two converging nappe systems, the NE-verging Shikar Beh Nappe and the SW-verging north Himalayan nappes. The D-2 Shikar Beh Nappe is characterized by isoclinal folding and top-to-the NE shearing, representing the main deformation in the High Himalayan Crystalline. D-2 also caused the main metamorphism in the High Himalayan Crystalline that was of a Barrovian-type, reaching upper amphibolite facies peak conditions. The Shikar Beh Nappe is interpreted to have formed within the Indian crust SW of the subduction zone. Simultaneously with NE-directed nappe formation, incipient subduction of India below Asia caused stacking of the SW-verging north Himalayan Nappes, that were thrust from the northern edge of the subducted continent toward the front of the Shikar Beh Nappe. As a result, the SW-verging folds of the D-3 Main Fold Zone formed in the Tethyan Himalaya below the front of the north Himalayan nappes. D-3 represents the main deformation in the Tethyan Himalaya, associated with a greenschist facies metamorphism. Folding within the Main Fold Zone subsequently propagated toward SW into the High Himalayan Crystalline, where it overprinted the preexisting D-2 structures. After subduction at the base of the north Himalayan nappes, the subduction zone stepped to the base of the High Himalayan Crystalline, where D-3 folds were crosscut by SW-directed D-4 thrusting. During D-4, the Crystalline Nappe, comprising the Main Fold Zone and relies of the Shikar Beh Nappe was thrust toward SW over the Lesser Himalayan Sequence along the 4 to 5 kms thick Main Central Thrust zone. Thrusting was related to a retrograde greenschist facies overprint at the base of the Crystalline Nappe and to pro-grade greenschist facies conditions in the Lesser Himalayan Sequence. Simultaneously with thrusting at the base of the Crystalline Nappe, higher crustal levels were affected by NE-directed D-5 normal extensional shearing and by dextral strike-slip motion, indicating that the high-grade metamorphic Crystalline Nappe was extruded between the low-grade metamorphic Lesser Himalayan Sequence at the base and the north Himalayan nappes at the top. The upper boundary of the Crystalline Nappe is not clearly delimited and passes gradually into the low-grade rocks at the front of the north Himalayan nappes. Extrusion of the Crystalline Nappe was followed by the phase D-6, characterized by large-scale, upright to steeply inclined, NE-verging folds and by another series of normal and extensional structures D-7+D-8 that may be related to ongoing extrusion of the Crystalline Nappe. The late stage evolution is represented by the phases D-A and D-B that indicate shortening parallel to the axis of the mountain chain and by D-C that is interpreted to account for the formation of large-scale domes with NNW-SSE-trending axes, an example of which is exposed in the Larji-Kullu-Rampur tectonic window.

Assistência multiprofissional na reabilitação da comunicação da pessoa laringectomizada

Este artigo tem como objetivo divulgar a experiência de um grupo de profissionais envolvidos na reabilitação e na reabilitação vocal dos laringectomizados que participam do GARPO- Laringectomizados. São descritas as diferentes possibilidades de reabilitação vocal para o laringectomizado como também, os pressupostos que permeiam todas as atividades e etapas do processo. Destaca-se as características da pessoas laringectomizadas, as conseqüências da cirurgia, o significado de ser laringectomizado que direcionam a assistência do enfermeiro no processo, em integração com o fonoaudiólogo.

The molecular architecture of the TNF superfamily.

Ligands of the TNF (tumour necrosis factor) superfamily have pivotal roles in the organization and function of the immune system, and are implicated in the aetiology of several acquired and genetic diseases. TNF ligands share a common structural motif, the TNF homology domain (THD), which binds to cysteine-rich domains (CRDs) of TNF receptors. CRDs are composed of structural modules, whose variation in number and type confers heterogeneity upon the family. Protein folds reminiscent of the THD and CRD are also found in other protein families, raising the possibility that the mode of interaction between TNF and TNF receptors might be conserved in other contexts.

The fetal membranes of the otter shrews and a synapomorphy for afrotheria.

The otter shrews of mainland Africa are the closest relatives of the Madagascar tenrecs. We sought for similarities in placentation between the two groups and, in a wider context, with other mammals of the Afrotheria clade. Specimens of the Nimba otter shrew (Micropotamogale lamottei) were obtained from the Ivory Coast and examples of the giant otter shrew (Potamogale velox) from the Hill Collection. The Nimba otter shrew has a central haemophagous organ similar to that in tenrecs. The labyrinth of the Nimba otter shrew, however, is endotheliochorial with syncytial trophoblast enclosing the maternal vessels. On the other hand tenrecs have cellular haemomonochorial placentae and an associated spongy zone, which is not present in the Nimba otter shrew. The placenta of the giant otter shrew is also endotheliochorial. The central region of its placenta is particularly interesting, since the juxtafetal portion is clearly a haemophagous region whereas the labyrinth feeding this region is endotheliochorial. Thus there is considerable variation in placental morphology within Tenrecidae. Importantly, however, both otter shrews have a large allantoic sac divided into four intercommunicating lobes by two pairs of septal folds. A similar arrangement has been described for representatives of each of the remaining five orders within Afrotheria. This is significant because previous anatomical studies have failed to establish a single synapomorphy in support of Afrotheria.

La comunicació política de Jordi Pujol

En el treball que es desenvolupa a continuació s’analitza el perfil comunicatiu de Jordi Pujol i Soley, expresident de la Generalitat de Catalunya. L’objectiu de l’estudi és analitzar els diferents elements de la vida personal i professional de l’expresident posant-los en relació amb la seva faceta comunicativa per tal d’acabar determinant els elements clau de la seva comunicació política. El treball s’inicia amb una breu biografia, personal i professional, de l’expresident de la Generalitat de Catalunya que dóna peu a l’anàlisi de les facetes que el posicionaren com a líder. Seguidament, s’estudia l’electorat i el procés mental que aquest desenvolupa al rebre informació per part dels polítics per, finalment, acabar estudiant en detall la comunicació política a nivell verbal, vocal i visual del subjecte d’estudi.

Big brother is watching you: eavesdropping to resolve family conflicts

Adult animals can eavesdrop on behavioral interactions between potential opponents to assess their competitive ability and motivation to contest resources without interacting directly with them. Surprisingly, eavesdropping is not yet considered as an important factor used to resolve conflicts between family members. In this study, we show that nestling barn owls (Tyto alba) competing for food eavesdrop on nestmates' vocal interactions to assess the dominance status and food needs of opponents. During a first training playback session, we broadcasted to singleton bystander nestlings a simulated vocal interaction between 2 prerecorded individuals, 1 relatively old (i.e., senior) and 1 younger nestling (i.e., junior). One playback individual, the "responder," called systematically just after the "initiator" playback individual, hence displaying a higher hunger level. To test whether nestlings have eavesdropped on this interaction, we broadcasted the same prerecorded individuals separately in a subsequent playback test session. Nestlings vocalized more rapidly after former initiators' than responders' calls and they produced more calls when the broadcasted individual was formerly a junior initiator. They chiefly challenged vocally juniors and initiators against whom the likelihood of winning a vocal contest is higher. Owlets, therefore, identified the age hierarchy between 2 competitors based on their vocalizations. They also memorized the dynamics of competitors' previous vocal interactions, and used this information to optimally adjust signaling level once interacting with only 1 of the competitor. We conclude that siblings eavesdrop on one another to resolve conflicts over parental resources.