Rheological, mechanical and membrane penetration properties of novel dual drug systems for percutaneous delivery

In this study it has been demonstrated that mixtures of two solid drugs, ibuprofen and methyl nicotinate, with different but complementary pharmacological activities and which exist as a single liquid phase over a wide composition range at skin temperature, can be formulated as o/w emulsions without the use of an additional hydrophobic carrier. These novel dual drug systems provided significantly enhanced in vitro penetration rates through a model lipophilic barrier membrane compared to conventional individual formulations of each active. Thus, for ibuprofen, drug penetration flux enhancements of three- and 10-fold were observed when compared to an aqueous ibuprofen suspension and a commercial alcohol-based ibuprofen formulation, respectively. Methyl nicotinate penetration rates were shown to be similar for aqueous gels and emulsified systems. Mechanisms explaining these observations are proposed. Novel dual drug formulations of ibuprofen and methyl nicotinate, formulated within the liquid range at skin temperature, were investigated by oscillatory rheology and texture profile analysis. demonstrating the effects of drug and viscosity enhancer concentrations, and disperse phase type upon the rheological, mechanical and drug penetration properties of these systems. (C) 2000 Elsevier Science B.V. All rights reserved.

A double-blind cross-over study of nifedipine retard in patients with Raynaud's phenomenon

The effectiveness of nifedipine retard as a treatment for Raynaud's phenomenon was assessed in 15 patients in a placebo controlled double blind study. An associated connective tissue disease was evident in 7 patients. Changes in finger and forearm blood flow (venous occlusion plethysmography), digital skin temperature and digital systolic pressure were measured acutely before and after a 2-week treatment period. Subjective assessment of efficacy was based on patient diary data. In addition alpha 2-adrenoceptor density on platelets was measured before and after chronic nifedipine therapy in both the patient group and in an age-and-sex-matched control group. No significant haemodynamic changes were observed. Nifedipine retard significantly reduced the frequency (p less than 0.05) with no change in either the duration or severity of vasospastic attacks. Side effects were common following nifedipine retard. A reduction in alpha 2-adrenoceptor density on platelets was observed in patients compared to a control group (p less than 0.05). Alpha 2-adrenoceptor density was unchanged following a 2-week treatment period with nifedipine retard. This study concludes that nifedipine retard is not effective in the treatment of Raynaud's phenomenon over a short time course. Patients with Raynaud's phenomenon have reduced alpha 2-adrenoceptor densities on their platelets.

The sympathetic release test: a test used to assess thermoregulation and autonomic control of blood flow

When a subject is heated, the stimulation of temperature-sensitive nerve endings in the skin, and the raising of the central body temperature, results in the reflex release of sympathetic vasoconstrictor tone in the skin of the extremities, causing a measurable temperature increase at the site of release. In the sympathetic release test, the subject is gently heated by placing the feet and calves in a commercially available foot warming pouch or immersing the feet and calves in warm water and wrapping the subject in blankets. Skin blood flow is estimated from measurements of skin temperature in the fingers. Normally skin temperature of the fingers is 65-75 degrees F in cool conditions (environmental temperature: 59-68 degrees F) and rises to 85-95 degrees F during body heating. Deviations in this pattern may mean that there is abnormal sympathetic vasoconstrictor control of skin blood flow. Abnormal skin blood flow can substantially impair an individual's ability to thermoregulate and has important clinical implications. During whole body heating, the skin temperature from three different skin sites is monitored and oral temperature is monitored as an index of core temperature. Students determine the fingertip temperature at which the reflex release of sympathetic activity occurs and its maximal attainment, which reflects the vasodilating capacity of this cutaneous vascular bed. Students should interpret typical sample data for certain clinical conditions (Raynaud's disease, peripheral vascular disease, and postsympathectomy) and explain why there may be altered skin blood flow in these disorders.

Estudo exploratório da excitabilidade axonal com a "técnica threshold tracking" : controlos saudáveis e doentes com polineuropatia amilóide familiar

Tese de mestrado, Neurociências, Faculdade de Medicina, Universidade de Lisboa, 2015

Characterising Behavioural Thermoregulation in the Bearded Dragon: The Role of TRPM8

Temperature regulation is a necessary part of maintaining life, as most biological processes are influenced by temperature. ThermoTRP channels are considered the primary thermosensors in endotherms, but little is known regarding their function in ectotherms. The goal of this study is to establish TRPM8, a cold sensing channel, as a participant in normal thermoregulation of the bearded dragon (Pogona vitticeps), an ectotherm. Animals were placed inside a ramping temperature shuttle box to assess the common behavioural thermoregulatory strategy of shuttling. Shuttling involves the periodic movement between cold and warm environments to maintain body temperature at moderate levels. The temperatures for cold and warm escapes represent sensory thresholds for inducing the shuttling thermoeffector. Animals were administered with: 1) an injection of the TRM8 antagonist capsazepine, 2) an injection of the TRPM8 agonist menthol, and 3) menthol applied topically. No effect was observed with injected drugs, but topical menthol resulted in a 2-3oC rise in the ambient temperature threshold and 1-2oC rise in skin temperature threshold for escape from the cold compartment. In an additional experiment, gaping behaviour, a warm temperature thermoregulatory strategy, was assessed. No effect was observed in this behaviour when the same dose of menthol was applied topically. These results point to a role for TRPM8 only in thermoregulation as it relates to cold temperature sensation in lizards, since it does not participate in regulating warm temperature behaviours such as gaping.

Antiobesity and antidiabetic activity of P. balsamifera, its active Salicortin, and L. laricina, medicinal plants from the traditional pharmacopoeia of the James Bay Cree

La prévalence de l’obésité, du diabète de type 2, et du syndrome métabolique, sont à la hausse chez les Cris d’Eeyou Istchee (CEI-Nord du Québec). Ces problèmes sont aggravés par leur diète non traditionnelle, leur sédentarité, ainsi que par une résistance culturelle aux produits pharmaceutiques. Afin de développer des traitements antidiabétiques culturellement adaptés, notre équipe a effectué une enquête ethnobotanique qui a identifié 17 plantes provenant de la pharmacopée traditionnelle des CEI. À partir des études de criblage effectuées in vitro, deux plantes parmi les 17 ont attiré notre attention. Populus balsamifera L. (Salicaceae) pour ses propriétés anti-obésité et Larix laricina K. Koch (Pinaceae) pour ses propriétés antidiabétiques. P. balsamifera et son composé actif salicortin ont inhibé l’accumulation de triglycérides durant l’adipogénèse dans les adipocytes 3T3-L1. L. laricina a augmenté le transport de glucose et l’activation de l’AMPK dans les cellules musculaires C2C12, l’adipogénèse dans les 3T3-L1 et a démontré un fort potentiel découpleur (propriété anti-obésité). Les objectifs de cette thèse sont d'évaluer les potentiels anti-obésité et antidiabétique et d’élucider les mécanismes d'action de P. balsamifera, salicortin, et L. laricina chez la souris C57BL/6 rendue obèse par une diète riche en gras (HFD). Les souris ont été soumises pendant huit (étude préventive) ou seize semaines (étude traitement) à une HFD, ou à une HFD dans laquelle P. balsamifera, salicortin, ou L. laricina a été incorporé soit dès le départ (prévention), ou dans les 8 dernières des 16 semaines d'administration de HFD (traitement). iv Les résultats démontrent que P. balsamifera (dans les deux études) et salicortin (évalué dans l’étude traitement) diminuent: le poids corporel, le gras rétropéritonéal, la sévérité de la stéatose et l’accumulation de triglycérides hépatique (ERK impliqué), les niveaux de glycémie et d'insuline, et le ratio leptine/adiponectine. Dans les deux études, P. balsamifera a significativement réduit la consommation de nourriture mais cet effet coupe-faim nécessite d’être approfondi. Dans l'étude préventive, P. balsamifera a augmenté la dépense énergétique (hausse de la température à la surface de la peau et de l’activation de la protéine découplante-1; UCP-1). Les voies de signalisation activées par P. balsamifera et par salicortin (de façon plus modeste) sont impliquées dans: la production de glucose hépatique (Akt), l’expression de Glut4 dans le muscle squelettique, la captation du glucose et du métabolisme des lipides (Akt dans le tissu adipeux), la différenciation des adipocytes (ERK et PPARg), l’inflammation dans le foie (IKKαβ), et l'oxydation des acides gras dans le muscle, le foie, ou le tissu adipeux (PPARa et CPT-1). D’autre part, L. laricina a également diminué les niveaux de glycémie et d’insuline, le ratio leptine/adiponectine, le gras rétropéritonéal et le poids corporel. Ces effets ont été observés en conjonction avec une augmentation de la dépense énergétique: hausse de température à la surface de la peau (prévention) et amélioration de la fonction mitochondriale et de la synthèse d'ATP (traitement). En conclusion, l’utilisation de P. balsamifera, salicortin et L. laricina comme des traitements alternatifs et culturellement adaptés aux CEI représente une contribution importante dans la prévention et le traitement de l’obésité et du diabète.

Psychophysiological responses to appraisal dimensions in a computer game

A computer game was used to study psychophysiological reactions to emotion-relevant events. Two dimensions proposed by Scherer (1984a, 1984b) in his appraisal theory, the intrinsic pleasantness and goal conduciveness of game events, were studied in a factorial design. The relative level at which a player performed at the moment of an event was also taken into account. A total of 33 participants played the game while cardiac activity, skin conductance, skin temperature, and muscle activity as well as emotion self-reports were assessed. The self-reports indicate that game events altered levels of pride, joy, anger, and surprise. Goal conduciveness had little effect on muscle activity but was associated with significant autonomic effects, including changes to interbeat interval, pulse transit time, skin conductance, and finger temperature. The manipulation of intrinsic pleasantness had little impact on physiological responses. The results show the utility of attempting to manipulate emotion-constituent appraisals and measure their peripheral physiological signatures.

The use of wireless data communication and body sensing devices to evaluate occupants' comfort in buildings

Physiological parameters measured by an embedded body sensor system were demonstrated to respond to changes of the air temperature in an office environment. The thermal parameters were monitored with the use of a wireless sensor system that made possible to turn any existing room into a field laboratory. Two human subjects were monitored over daily activities and at various steady-state thermal conditions when the air temperature of the room was altered from 22-23°C to 25-28°C. The subjects indicated their thermal feeling on questionnaires. The measured skin temperature was distributed close to the calculated mean skin temperature corresponding to the given activity level. The variation of Galvanic Skin Response (GSR) reflected the evaporative heat loss through the body surfaces and indicated whether sweating occurred on the subjects. Further investigations are needed to fully evaluate the influence of thermal and other factors on the output given by the investigated body sensor system.

A critical evaluation of the ability of the Spinning Enhanced Visible and Infrared Imager (SEVIRI) thermal infrared red-green-blue rendering to identify dust events: theoretical analysis

Using a combination of idealized radiative transfer simulations and a case study from the first field campaign of the Saharan Mineral Dust Experiment (SAMUM) in southern Morocco, this paper provides a systematic assessment of the limitations of the widely used Spinning Enhanced Visible and Infrared Imager (SEVIRI) red-green-blue (RGB) thermal infrared dust product. Both analyses indicate that the ability of the product to identify dust, via its characteristic pink coloring, is strongly dependent on the column water vapor, the lower tropospheric lapse rate, and dust altitude. In particular, when column water vapor exceeds ∼20–25 mm, dust presence, even for visible optical depths of the order 0.8, is effectively masked. Variability in dust optical properties also has a marked impact on the imagery, primarily as a result of variability in dust composition. There is a moderate sensitivity to the satellite viewing geometry, particularly in moist conditions. The underlying surface can act to confound the signal seen through variations in spectral emissivity, which are predominantly manifested in the 8.7μm SEVIRI channel. In addition, if a temperature inversion is present, typical of early morning conditions over the Sahara and Sahel, an increased dust loading can actually reduce the pink coloring of the RGB image compared to pristine conditions. Attempts to match specific SEVIRI observations to simulations using SAMUM measurements are challenging because of high uncertainties in surface skin temperature and emissivity. Recommendations concerning the use and interpretation of the SEVIRI RGB imagery are provided on the basis of these findings.

Exercise-associated thermographic changes in young and elderly subjects

This study aimed at evaluating the thermographic changes associated with localized exercise in young and elderly subjects. An exercise protocol using 1 kg load was applied during 3 min to the knee flexors of 14 elderly (67 +/- 5 years) and 15 young (23 +/- 2 years) healthy subjects. The posterior thigh`s skin temperature of the exercised limb and contralateral limb were measured by infrared thermography on pre-exercise, immediately post-exercise, and during the 10-min period post-exercise. Difference (p < 0.01) between elderly and young subjects was observed on pre-exercise temperature. Although differences were not observed between pre-exercise and immediately post-exercise temperature in the exercised limb, thermographic profile displayed heat concentration in exercised areas for both groups. Temperature reduction was only observed for the young group on the 10-min post-exercise (p < 0.05) in the exercised limb (30.7 +/- 1.7 to 30.3 +/- 1.5 degrees C). In contrast, there was a temperature reduction post-exercise (p < 0.01) in the contralateral limb for both groups. These results present new evidences that elderly and young subjects display similar capacity of heat production; however, the elderly subjects presented a lower resting temperature and slower heat dissipation. This work contributes to improve the understanding about temperature changes in elderly subjects and may present implications to the sports and rehabilitation programs.

Influence of the single or combined administration of cocaine and testosterone in autonomic and neuroendocrine responses to acute restraint stress

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Zoneamento bioclimático da ovinocultura no Estado do Paraná

Utilizaram-se 45 fêmeas ovinas adultas (15 Hampshire Down [HD], 15 Texel [TE] e 15 Ile de France [IF]), para propor um zoneamento bioclimático da ovinocultura no Estado do Paraná. Mediram-se a temperatura retal (Tr), da epiderme (Te), do interior do velo (Tiv) e da superfície do velo (Tsv); a frequência respiratória (Fr); a temperatura do ar (Ta), pressão de vapor (e), velocidade do vento (v) e carga térmica radiante (CTR). O Índice de Conforto Térmico utilizado foi ICT= 0,6678Ta + 0,4969e + 0,5444Tg + 0,1038v. A regressão do ICT sobre Tr mostrou efeito quadrático para as três raças. Para ICT=24,3, 27,3 e 20,6, os valores de Tr foram respectivamente: 39,10ºC para a raça HD, 39,05ºC para TE e 39,09ºC para IF, atingindo 40,40; 40,50; e 40,28ºC, respectivamente, para ICT=58. As três raças aumentaram sua Tr a partir de ICT=26, com a TE apresentando menor Tr até o valor ICT=46; neste ponto, as três raças foram semelhantes, tendo a TE apresentado maiores valores. Para ICT igual a 27,6; 29,7; e 27,0, os valores de Fr foram, respectivamente, 89,63; 77,08; e 78,77 resp./min., para as raças HD, TE e IF. A raça TE apresentou menor Fr (77,08 resp./min.), para ICT=29,7 e para ICT=48, valores semelhantes aos da IF (181,96 resp./min.); a partir deste índice, passou a ser maior que as demais raças, atingindo valores de 288,66 resp./min. no ICT=56, porém inferior à HD (289,01 resp./min.). Neste índice, a raça IF foi a que apresentou a menor Fr (275,72 resp./min.). Uma extensa faixa ao longo do litoral do Estado, entrando cerca de 200 km para o interior até os limites das cidades de Castro, Telêmaco Borba, Laranjeiras do Sul e Pato Branco, permite a criação das três raças, sem exigir grandes esforços de termorregulação.

Índice fuzzy de conforto térmico para frangos de corte

A estimativa de conforto térmico na avicultura moderna é importante para que sistemas de climatização possam ser acionados no tempo correto, diminuindo perdas e aumentando rendimentos. Embora a literatura corrente apresente alguns índices de conforto térmico, que são aplicados para essa estimativa, estes são baseados apenas em condições do ambiente térmico e não consideram fatores importantes inerentes aos animais, tais como genética e capacidade de aclimatação, provendo, geralmente, uma estimativa inadequada do conforto térmico das aves. Este trabalho desenvolveu o Índice Fuzzy de Conforto Térmico (IFCT), com o intuito de estimar o conforto térmico de frangos de corte, considerando que o mecanismo usado pelas aves para perda de calor em ambientes fora da zona termoneutra é a vasodilatação periférica, que aumenta a temperatura superficial, e que pode ser usada como indicador do estado de conforto. O IFCT foi desenvolvido a partir de dois experimentos, que proporcionaram 108 cenários ambientais diferentes. Foram usadas imagens termográficas infravermelhas, para o registro dos dados de temperaturas superficiais das penas e da pele, e o grau de empenamento das aves. Para os mesmos cenários de ambiente térmico observados nos experimentos, foram comparados os resultados obtidos usando o IFCT e o Índice de Temperatura e Umidade (ITU). Os resultados validaram o IFCT para a estimativa do conforto térmico de frangos de corte, sendo específico na estimativa de condições de perigo térmico, usual em alojamentos em países de clima tropical. Essa característica é desejável em modelos que estimem o bem-estar térmico de frangos de corte, pois situações classificadas como perigo acarretam no dispêndio de recursos para evitar perdas produtivas.

Efeitos da temperatura e da movimentação do ar sobre o isolamento térmico do velo de ovinos em câmara climática

Foram utilizados dez ovinos da raça Corriedale - cinco machos e cinco fêmeas com pesos entre 52,2 e 87,6 kg - com o objetivo de avaliar o efeito da combinação da movimentação do ar (0 e 5,0 m/s) com a temperatura do ar (25, 30 e 40ºC) sobre a temperatura retal (T R, ºC), da epiderme (T E, ºC), da superfície do velo (T V, ºC) e do interior do velo (T I, ºC) e a espessura do velo (E V, cm) e suas relações com o isolamento térmico do velo. A presença de vento não teve efeito sobre as variáveis estudadas, o que sugere que fluxo de ar (<5,0 m/s) paralelo ao eixo corporal do animal tem pouco efeito sobre o isolamento térmico do velo, independentemente da temperatura do ar, que se mostrou altamente correlacionada, de forma positiva, com as temperaturas retal, do velo, do interior do velo e da epiderme. Sob temperaturas inferiores a 30ºC, a transferência de calor através do velo ocorreu via condução e convecção livre, enquanto sob altas temperaturas (>40ºC) o fluxo de calor sensível não foi significativa.

BLOQUEIO PERIDURAL E TERMOMETRIA CUTANEA COMO CRITERIO PARA INDICACAO CIRURGICA DE SIMPATECTOMIA LOMBAR

To find a valuable tool in achieving a good accuracy in predicting the outcome from sympathectomy, changes in limb skin temperatures (LST) before and after epidural lumbar anesthesia (ELA) and before and after lumbar sympathectomy were studied in 13 patients with thrombangiitis obliterans or arteriosclerosis obliterans. The results were compared with the clinical course and follow-up from 1 to 5 years. In seven patients there was a rise in LST after ELA and after sympathectomy, and this pattern of variation was associated with good clinical course. In three patients there was decrease in the LST after ELA and after sympathectomy and they did not do well. In two patients there was no change in temperature before or after the procedure; one of them had a good and the other a bad clinical course. The same measurements were performed in three other patients who had had a sympathectomy some years previously and the data showed that LST was lowered after ELA. It is concluded that the measurement of limb skin temperature before and after epidural lumbar anesthesia aids in determining which patients are more likely to benefit from sympathectomy.