Hematomas and limb skeletal malformations in chicken embryos following exposure to 5-fluoro-2-deoxyuridine

Despite considerable attention to community integration and related topics in the past decades, a clear definition of community integration continues to elude researchers and service providers. Common to most discussions of the topic, however, are three ideas: that integration involves relationships with others, independence in one's living situation and activities to fill one's time. The present study sought to expand this conceptualization of community integration by asking people with brain injuries for their own perspectives on community integration. This qualitative study resulted in a definition of community integration consisting of nine indicators: orientation, acceptance, conformity, close and diffuse relationships, living situation, independence, productivity and leisure. These indicators were empirically derived from the text of 116 interviews with people with moderate-severe brain injuries living in the community. Eighteen adults living in supported living programmes were followed for 1 year, to track their evolving definition of integration and the factors they felt were related to integration. The study also showed a general trend toward more positive evaluation over the year, and revealed that positive evaluation was frequently related to meeting new people and freedom from staff supervision. These findings are interpreted in the light of recommendations for community programmes.     

A labeled guanidine ligand for studying sweet taste

A synthesis of a biotinylated-, coumarin-substituted-N,N'-diarylguanidine 1 is reported. This ligand has structural features conducive to studying sweet taste including a fluorescent tag to facilitate spectroscopic studies of binding to protein-receptors for sweet ligands and an anchor for affinity purification.     

Cerebral vasculopathy and neurologic sequelae in infants with cervicofacial hemangioma: report of eight patients

It is well known that the oral bioavailability of peptide and protein drugs is generally poor because they are extensively degraded by proteases in the gastrointestinal tract and impermeable through the intestinal mucosa. Therefore, various approaches have been examined to overcome the delivery problems of these peptides and to improve their absorption via the gastrointestinal tract. Of these approaches, a potentially useful approach to solve these delivery problems may be chemical modification of peptides and proteins to produce prodrugs and analogues. Thus, it is plausible that this approach may protect peptides against degradation by peptidases and other enzymes present at the mucosal barrier and renders the peptides and proteins more lipophilic, resulting in increased bioavailability. From these standpoints, we synthesized lipophilic derivatives of peptides and proteins such as thyrotropin-releasing hormone (TRH), tetragastrin (TG), calcitonin and insulin by chemical modification with fatty acids. The pharmacological activities of these derivatives were relatively high as compared with the native peptides. A significant increase in the intestinal absorption of these derivatives of peptides was observed in comparison with native peptides. Overall, the effects of acylation on the intestinal absorption of these peptides were more predominant in the large intestine than those in the small intestine. In addition, these derivatives were more stable than the parent peptides in homogenates of the various intestinal mucosae. We also examined the intestinal transport characteristics of TG and its acyl derivatives using Caco-2 cell monolayers in order to assess the contribution of enzymatic and transport barriers on their intestinal absorption. The degradation clearance of TG on the apical membrane was decreased by chemical modification with fatty acids. In addition, the permeability clearance of TG was improved by the acylation. On the other hand, the intestinal absorption of thyrotropin releasing hormone (TRH), which is transported by a carrier-mediated process, was also enhanced by chemical modification with lauric acid. In summary, this chemical modification approach may be useful to improve the intestinal absorption of peptide and protein drugs.     

Cerebral ventricle-brain ratio in monozygotic twins discordant and concordant for schizophrenia

The influence of tetrapeptide tuftsin (Tyr-Lys-Pro-Arg) on learning, exploratory activity, emotional behavior, and hypothalamic monoamine content was studied in Wistar rats with different resistance to stress induced by acoustic stimuli. Positive effects of taftsin were more pronounced in low-resistant rats. Administration of taftsin induced in these animals a significant increase in reactivity to stimuli of different modalities, the open-field exploratory activity, rate of alimentary conditioning and its modification in emotionally negative situation. Biochemical examinations showed that in rats with high resistance to stress taftsin administration led to a decrease in hypothalamic noradrenaline level and increase in dopamine and serotonin levels. On the contrary, in low-resistant animals taftsin increased the level of noradrenaline and decreased that of dopamine, serotonin, and 5-hydroxyindoleacetic acid. It is suggested that different behavioral effects of taftsin in stress-resistant and nonresistant rats are caused by its different influence on hypothalamic biogenic amines.     

Recurrent bleb infections

AIM: To report the patient characteristics, causative organisms, and clinical outcomes in patients with recurrent bleb related ocular infections. METHODS: The medical records of all patients diagnosed with bleb related ocular infection at the New York Eye and Ear Infirmary over a 10 year period were reviewed. Recurrent bleb infection was defined as at least two episodes of bleb purulence with or without associated intraocular inflammation separated by a quiescent period of at least 3 months. RESULTS: Recurrent bleb infections developed in 12 eyes of 12 patients (10 men, two women) a mean of 16.3 (SD 17.9) months (range 3-51 months) after the initial infection. Two patients developed a third episode 3 and 20 months, respectively, after the second infection, yielding a total of 14 recurrent infection episodes. Recurrent infection developed after trabeculectomy in 11 eyes (adjunctive 5-fluorouracil, nine eyes; mitomycin C, one eye; no antifibrosis agent, one eye) and following cataract extraction with inadvertent bleb formation in one eye. Four (36.4%) of the filtered eyes had undergone trabeculectomy at the inferior limbus. The mean follow up time from filtering surgery to the first bleb related infection was 28 months for the nine patients treated with 5-fluorouracil and 14 months for the single patient treated with mitomycin C. 11 (78.6%) cases had a documented bleb leak in the 4 week period before or at the time of recurrent infection. Topical, prophylactic antibiotics had been used in 7/14 (50%) cases. The same organism was cultured from the initial and recurrent infections in 2/14 (14.3%) cases. CONCLUSION: Eyes that have been successfully treated for bleb related infection remain at risk for recurrent infection. No apparent correlation exists between organisms responsible for the initial and recurrent infections. The increased rate of recurrent bleb related infection in patients receiving adjunctive 5-fluorouracil compared to mitomycin C may have been related to the longer follow up of the 5-fluorouracil eyes.     

Cyclic AMP regulates potassium channel expression in C6 glioma by destabilizing Kv1.1 mRNA

The tissue distributions and physiological properties of a variety of cloned voltage-gated potassium channel genes have been characterized extensively, yet relatively little is known about the mechanisms controlling expression of these genes. Here, we report studies on the regulation of Kv1.1 expressed endogenously in the C6 glioma cell line. We demonstrate that elevation of intracellular cAMP leads to the accelerated degradation of Kv1.1 RNA. The cAMP-induced decrease in Kv1.1 RNA is followed by a decrease in Kv1. 1 protein and a decrease in the whole cell sustained K+ current amplitude. Dendrotoxin-I, a relatively specific blocker of Kv1.1, blocks 96% of the sustained K+ current in glioma cells, causing a shift in the resting membrane potential from -40 mV to -7 mV. These data suggest that expression of Kv1.1 contributes to setting the resting membrane potential in undifferentiated glioma cells. We therefore suggest that receptor-mediated elevation of cAMP reduces outward K+ current density by acting at the translational level to destabilize Kv1.1 RNA, an additional mechanism for regulating potassium channel gene expression.