In vitro activities of pentamidine,pyrimethamine, trimethoprim,and sulfonamides against Aspergillus species

The susceptibilities of 70 strains of Aspergillus species were tested against seven different sulfa drugs and pentamidine by a microdilution method with RPMI 1640 and yeast nitrogen base media. Sulfamethoxazole, sulfadiazine, and pentamidine were active in vitro. The MICs obtained with RPMI 1640 were significantly higher than those with yeast nitrogen base. More studies are needed to further elucidate the action of these drugs.     

Efficacy of cidofovir in a murine model of disseminated progressive vaccinia

An animal model that mimics progressive disseminated vaccinia was elaborated. To this end nude (athymic) mice were inoculated intracutaneously with vaccinia virus in the lumbosacral area. Viral replication (DNA) in the skin was detected as early as day 2 postinfection (p.i.). Mice developed typical vaccinia lesions at the site of inoculation by day 4 to 6 p.i. By about 2 weeks p.i., the infection had spread all over the body, a situation reminiscent of disseminated vaccinia in humans. The infection resulted in viremia and spread of the virus to visceral organs, as well as to the brain. Topical treatment with cidofovir, initiated at the day of infection or at day 1 p.i., completely protected against virus-induced cutaneous lesions and against associated mortality. When treatment was initiated at a later time (day 2 to 5 p.i.), a partial but marked protective effect was noted, which can be explained by the fact that by that time, the virus had spread from the skin to the visceral organs. Next, infected animals were left untreated until the time ( approximately 2 weeks p.i.) at which disseminated vaccinia had developed. When systemic treatment with cidofovir was initiated at that time, it caused lesions to heal and regress. In most of these animals, lesions had completely (or almost completely) disappeared by day 10 to 15 after the start of therapy. The observation that cidofovir is able to cause healing of disseminated vaccinia lesions in animals should have implications for the therapy of complications of vaccination against smallpox.     

Frustrated and invisible--younger stroke patients' experiences of the rehabilitation process

PURPOSE: This study aimed to get knowledge of the younger stroke patient's viewpoint and to describe how young stroke patients experience the rehabilitation process. The purpose was also to develop hypotheses about the relationship between young stroke patients and the rehabilitation process. METHOD: Thematised in-depth interviews were performed with two women and three men who suffered from stroke (37 - 54 years). The analysis used was the Grounded Theory method of constant comparison. RESULTS: The analyses resulted in the core category 'Frustration' which was derived from the categories labelled 'The paralysed everyday' and 'Outside and invisible'. 'The paralysed everyday' category involved different aspects of everyday life after a stroke. Because of their fatigue they were unable to work and their family and social life were negatively affected. They found it difficult to engage in daily life activities and felt indifferent. The three women expressed frustration over the demands they experienced as being mothers and housekeepers, whereas the two men emphasised economic responsibility of the family as problematic. The category 'Outside and invisible' describes the lack of participation the informants experienced regarding the rehabilitation process. The informants felt they lacked information and age-adapted interventions. Their needs were not provided for and they felt distant from the other patients. Their remaining symptoms were probably on a cognitive basis and therefore invisible. This was a source of frustration. CONCLUSION: The hypotheses generated indicated that young stroke patients are frustrated and invisible due to the fact that the rehabilitation setting does not acknowledge the different needs of young stroke patients compared with older patients.     

Functionalized linear poly(amidoamine)s are efficient vectors for intracellular protein delivery

An effective intracellular protein delivery system was developed based on functionalized linear poly(amidoamine)s (PAAs) that form self-assembled cationic nanocomplexes with oppositely charged proteins. Three differently functionalized PAAs were synthesized, two of these having repetitive disulfide bonds in the main chain, by Michael-type polyaddition of 4-amino-1-butanol (ABOL) to cystamine bisacrylamide (CBA), histamine (HIS) to CBA, and ABOL to bis(acryloyl)piperazine (BAP). These water-soluble PAAs efficiently condense β-galactosidase by self-assembly into nanoscaled and positively-charged complexes. Stable under neutral extracellular conditions, the disulfide-containing nanocomplexes rapidly destabilized in a reductive intracellular environment. Cell-internalization and cytotoxicity experiments showed that the PAA-based nanocomplexes were essentially non-toxic. β-Galactosidase was successfully internalized into cells, with up to 94% of the cells showing β-galactosidase activity, whereas the enzyme alone was not taken up by the cells. The results indicate that these poly(amidoamine)s have excellent properties as highly potent and non-toxic intracellular protein carriers, which should create opportunities for novel applications in protein delivery.     

Psychosocial stress is associated with in vivo dopamine release in human ventromedial prefrontal cortex: a positron emission tomography study using [¹⁸F]fallypride

Rodent studies suggest that prefrontal dopamine neurotransmission plays an important role in the neural processing of psychosocial stress. Human studies investigating stress-induced changes in dopamine levels, however, have focused solely on striatal dopamine transmission. The aim of this study was to investigate in vivo dopamine release in the human prefrontal cortex in response to a psychosocial stress challenge, using the highly selective dopamine D?/? PET radioligand [1?F]fallypride in healthy subjects. Twelve healthy subjects (age (y): 39.8; SD=15.8) underwent a single dynamic Positron Emission Tomography (PET) scanning session after intravenous administration of 185.2 (SD=10.2) MBq [1?F]fallypride. Psychosocial stress was initiated at 100 min postinjection. PET data were analyzed using the linearized simplified reference region model (LSRRM), which accounts for time-dependent changes in [1?F]fallypride displacement. Voxel-based statistical maps, representing specific D?/? binding changes, were computed to localize areas with increased ligand displacement after task initiation, reflecting dopamine release. The psychosocial stress challenge induced detectable amounts of dopamine release throughout the prefrontal cortex, with dopaminergic activity in bilateral ventromedial prefrontal cortex being associated with subjectively rated experiences of psychosocial stress. The novel finding that a mild psychosocial stress in humans induces increased levels of endogenous dopamine in the PFC indicates that the dynamics of the dopamine-related stress response cannot be interpreted by focusing on mesolimbic brain regions alone.