Polycationic glycosides.

Cationic lipids have long been known to serve as antibacterial and antifungal agents. Prior efforts with attachment of cationic lipids to carbohydrate-based surfaces have suggested the possibility that carbohydrate-attached cationic lipids might serve as antibacterial and antifungal pharmaceutical agents. Toward the understanding of this possibility, we have synthesized several series of cationic lipids attached to a variety of glycosides with the intent of generating antimicrobial agents that would meet the requirement for serving as a pharmaceutical agent, specifically that the agent be effective at a very low concentration as well as being biodegradable within the organism being treated. The initial results of our approach to this goal are presented.

Behavioral factors of patients before and after diagnosis with melanoma: a cohort study - are sun-protection measures being implemented?

Melanoma is the deadliest form of all skin cancers and is highly linked to sun-related behavior in patients. However, sun-protection behavior to prevent melanoma in this population has been shown to be inadequate to date. The objective of this study was to compare changes in sun protection habit before and after patients' diagnosis with malignant melanoma. The study also seeks patients' advice on how to improve public education on melanoma prevention. A retrospective survey study was conducted on 68 respondents of patients diagnosed with melanoma from six different dermatologic practices in various boroughs of New York and Long Island in the state of New York by telephone interviews. There was a significant positive change in patients' sun-protection behavior after they were diagnosed with melanoma. Various methods of sun protection, such as avoiding sun exposure, applying and reapplying sunscreen, and wearing protective clothing were practiced more frequently after diagnosis. In addition, the frequency of sunbathing decreased drastically. Most patients were aware about the dangers of sun exposure before their diagnosis. They, however, did not feel the need to adopt sun-protection measures before their diagnosis. Respondents advised that education on dangers to excess sun exposure should be provided at an early age through multiple venues. The study reflected that 71% of diagnosed patients who completed the survey were informed about sun protection before their diagnosis. Many patients did not follow strict guidelines to prevent sun damage as shown by their behaviors before diagnosis. Diagnosis of the disease was apparently the main motivating factor to initiate challenging behavioral changes.

Polycations. 17. Synthesis and properties of polycationic derivatives of carbohydrates.

In our continuing investigation of polycationic salts for purposes of antimicrobial action, ion-channel blocking, and construction of ionic liquids, we have prepared several series of polycationic salts derived from carbohydrate precursors. These salts are currently being investigated for optimal efficacy as antibacterials and antifungals, as well as for other applications. The syntheses of such series of salts are described here along with preliminary antibacterial testing results and a discussion of their properties indicating their potential utility for several purposes.

Cohort study on patient response to botulinum toxin cosmetic therapy.

BACKGROUND: Botulinum toxin (BTX) therapy is currently the most popular cosmetic procedure in the United States. However, few studies exist regarding post-procedure perceptions of the patients' BTX therapy. OBJECTIVE: The aim of this cohort study was to determine patients' responses from pre- to post-BTX treatment experience. METHODS AND MATERIALS: One hundred twenty-three BTX patients of six different dermatologic cosmetic practices in various boroughs of New York and Long Island in the state of New York completed the questionnaire. Six hundred eighty-three surveys were sent out, and 123 completed surveys were obtained. Numerous questions were asked regarding how patients felt and responded towards the overall procedure of their BTX therapy. RESULTS: Eighty-eight percent of patients were satisfied or extremely satisfied with their dermatologists. Sixty-five percent of patients felt over 60% improvement in areas treated. Fifty-eight percent of patients anticipated making repeat visits, whereas the biggest concern for returning was due to the expensive cost of BTX. CONCLUSION: Our study correlated with previous studies done on retention rate of BTX cosmetic patients and satisfaction level on areas treated. The cost of BTX remained one of the primary concerns for repeat visits. Most patients were happy with their visits to the dermatology offices for BTX procedure, although things can be done to further enhance their visits and the likelihood that they will return.

Correlating efficacy in rodent cognition models with in vivo 5-hydroxytryptamine1a receptor occupancy by a novel antagonist, (R)-N-(2-methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl)-cyclohexane carboxamide (WAY-101405).

5-Hydroxytryptamine (5-HT)(1A) receptors play an important role in multiple cognitive processes, and compelling evidence suggests that 5-HT(1A) antagonists can reverse cognitive impairment. We have examined the therapeutic potential of a potent (K(i) = 1.1 nM), selective (>100-fold), orally bioavailable, silent 5-HT(1A) receptor antagonist (K(B) = 1.3 nM) (R)-N-(2-methyl-(4-indolyl-1-piperazinyl)-ethyl)-N-(2-pyridinyl)-cyclohexane carboxamide (WAY-101405). Oral administration of WAY-101405 was shown to be effective in multiple rodent models of learning and memory. In a novel object recognition paradigm, 1 mg/kg enhanced retention (memory) for previously learned information, and it was able to reverse the memory deficits induced by scopolamine. WAY-101405 (1 mg/kg) was also able to reverse scopolamine-induced deficits in a rat contextual fear conditioning model. In the Morris water maze, WAY-101405 (3 mg/kg) significantly improved learning in a paradigm of increasing task difficulty. In vivo microdialysis studies in the dorsal hippocampus of freely moving adult rats demonstrated that acute administration of WAY-101405 (10 mg/kg) increased extracellular acetylcholine levels. The selective radioligand [(3)H]WAY-100635, administered i.v., was used for in vivo receptor occupancy studies, where WAY-101405 occupied 5-HT(1A) receptors in the rat cortex, with an ED(50) value of 0.1 mg/kg p.o. Taken together, these studies demonstrate that WAY-101405 is a potent and selective, brain penetrant, orally bioavailable 5-HT(1A) receptor "silent" antagonist that is effective in preclinical memory paradigms at doses where approximately 90% of the postsynaptic 5-HT(1A) receptors are occupied. These results further support the rationale for use of this compound class in the treatment of cognitive dysfunction associated with psychiatric and neurological conditions.

A novel phosphodiesterase type 4 inhibitor, HT-0712, enhances rehabilitation-dependent motor recovery and cortical reorganization after focal cortical ischemia.

Rehabilitation-dependent motor recovery after cerebral ischemia is associated with functional reorganization of residual cortical tissue. Recovery is thought to occur when remaining circuitry surrounding the lesion is "retrained" to assume some of the lost function. This reorganization is in turn supported by synaptic plasticity within cortical circuitry and manipulations that promote plasticity may enhance recovery. Activation of the cAMP/CREB pathway is a key step for experience-dependent neural plasticity. Here we examined the effects of the prototypical phosphodiesterase inhibitor 4 (PDE4) rolipram and a novel PDE inhibitor (HT-0712), known to enhance cAMP/CREB signaling and cognitive function, on restoration of motor skill and cortical function after focal cerebral ischemia. Adult male rats were trained on a skilled reaching task to establish a baseline level of motor performance. Intracortical microstimulation was then used to derive high-resolution maps of forelimb movement representations within the caudal forelimb area of motor cortex contralateral to the trained paw. A focal ischemic infarct was created within approximately 30% of the caudal forelimb area. The effects of administering either rolipram or the novel PDE4 inhibitor HT-0712 during rehabilitation on motor recovery and restoration of movement representations within residual motor cortex were examined. Both compounds significantly enhanced motor recovery and induced an expansion of distal movement representations that extended beyond residual motor cortex. The expansion beyond the initial residual cortex was not observed in vehicle injected controls. Furthermore, the motor recovery seen in the HT-0712 animals was dose dependent. Our results suggest that PDE4 inhibitors during motor rehabilitation facilitate behavioral recovery and cortical reorganization after ischemic insult to levels significantly greater than that observed with rehabilitation alone.

IL-7 gene therapy in aging restores early thymopoiesis without reversing involution.

Thymic involution begins early in life and continues throughout adulthood, resulting in a decreased population of naive T cells in the periphery and a reduced ability to fight off newly encountered infectious diseases. We have previously shown that the first step of thymopoiesis is specifically blocked in aging. This block at the DN1 to DN2 transition and the subsequent loss of thymic output in old age mirrors the changes seen in IL-7-deficient mice, and it is hypothesized that decreased intrathymic IL-7 is involved in age-related thymic involution. To separate the effect of IL-7 on thymic involution from its function as a peripheral lymphocyte growth cofactor, we injected IL-7-secreting stromal cells into the thymi of recipient mice. The increased local concentration of IL-7 maintained the first step of thymopoiesis at a level far higher than was seen in age-matched controls. However, despite this success, there was no decrease in thymic involution or increase in T cell output. The inability of IL-7 to prevent involution led us to the discovery of an additional age-sensitive step in thymopoiesis, proliferation of the DN4 population, which is unaffected by IL-7 expression.