L-Ala-substituted rat galanin analogs distinguish between hypothalamic and jejunal galanin receptor subtypes

In order to explore which amino acids or which blocks of amino acids in the 29 amino acid neuropeptide galanin are important for recognition of the endogenous ligand by galanin receptor subtypes present in the jejunum and in the hypothalamus, respectively, we have carried out L-Ala substitutions of individual amino acids or of blocks of amino acids in the rat galanin sequence and examined the binding of the obtained analogs to the rat hypothalamic and jejunal galanin receptor subtypes. This study reveals that the galanin sequence YLLGPH^9–14 is essential for recognition of galanin by both the rat hypothalamic and jejunal galanin receptor subtypes. Substitution of the N-terminal amino acids, GWTL^1–4, leads to total loss of affinity of galanin for both hypothalamic and jejunal galanin receptors. The α-helical C-terminal amino acid (25–29) part of galanin has no greater influence on the affinity of galanin to the hypothalamic galanin receptor subtype. L-Ala substitution of the C-terminal amino acids of galanin KHGLT^25–29 shows, however, that this C-terminal motif is essential for the recognition by the jejunal galanin receptor subtype, whereas amino acids in the middle portion of galanin NSAG^5–8 are of importance for binding to the hypothalamic but not to the jejunal receptor. [Ala^5–8] Galanin thus has a more than 100-fold higher affinity to jejunal receptor than to the hypothalamic receptor, while [Ala^25–29] galanin has a more than 100-fold higher affinity for the hypothalamic than for jejunal galanin receptor subtypes. pH dependence of the galanin binding to these receptor subtypes is also different. © Munksgaard 1997.     

Child sexual abuse--children and families referred to a treatment project and the effects of intervention.

The characteristics of a series of 274 families who were referred to a sexual abuse treatment programme were analysed. Information was obtained on 411 abused children and 362 non-abused children. Different forms of sexual abuse were noted, with 77% of girls and 23% of boys affected. Boys tended to be abused at a younger age, more severely, and for longer periods than girls. There was a predominance of lower social class groups among the parents, and a wide variety of family structures, with reasonable stability over time. Ninety six per cent of perpetrators were men, and biological and step-parents predominated. Contributing factors in both the family history and the current perpetrators and their wives included sexual abuse, violence, chaotic families, marital problems, sexual difficulties, alcoholism, and subnormality. Follow up of 120 families, 180 victims, and 226 siblings showed that prosecution occurred in 60% of cases, with a high percentage of perpetrators being imprisoned. Treatment was offered to 87% of families, but because the treatment programme was in the early stages of development a variable number of children and parents were offered family treatment or treatment in groups for parents and children separately. There was an improvement in the victim's circumstances in 61% of cases, and a noticeable reduction in "sexualised" and general emotional difficulties among victims, but there was reabuse rate of 16%. Protection of children was achieved through changes of family attitude and changes in family structure including divorce and separation: 14% of victims were rehabilitated to both parents, 33% to mothers only, and 26% to new families or other residences. Consensus in the family that abuse had occurred was seen as an important factor in determining which children could be rehabilitated with both their parents, with their mothers only, or with new families; which families could be offered or accepted treatment; and whether positive changes in the family occurred.     

Safety, efficacy, and lipid profile of doxazosin at a VA medical center

The Veterans Administration Lakeside Medical Center (VALMC) is a 500-bed hospital located in downtown Chicago providing a broad scope of inpatient and outpatient medical services for more than 12,000 veterans. The VALMC Pharmacy and Therapeutics Committee requested a study to evaluate doxazosin mesylate (Cardura) to determine if this agent would be an acceptable alternative to other formulary agents. It appears that doxazosin provides several therapeutic advantages, including once-daily dosing, when compared with other more costly antihypertensive agents.     

Will diminishing cochlear delay affect speech perception in noise?

Objective: Normal auditory systems appear well habituated to time/phase delays inherent to sound encoding along the hearing organ, sending frequency information non-simultaneously to the central auditory system. Eliminating, or simply perturbing, the cochlear delay might be expected to decrease speech recognition ability, especially under demanding listening conditions. Resources of a larger-scale investigation permitted a preliminary examination of this issue, particularly on a relevant timescale of empirically demonstrated cochlear delays. Design: In a randomized controlled trial study, word recognition was tested for mono-syllabic tokens treated digitally to exacerbate, if not diminish/nullify, such delays. Speech-weighted noise was used to interfere with listening to time-frequency reversed (nominally no delay) versus non-reversed (natural timing) transforms under three treatments of speech tokens: (1) original-digitally recorded; digitally processed to emphasize (2) transient versus (3) quasi-steady-state components. Study sample: Ten normal-hearing young-adult females. Results: The findings failed to demonstrate statistically significant differences between delay conditions for any of the three speech-token treatments. Conclusions: An algorithm putatively diminishing frequency-dependent cochlear delays failed to systematically deteriorate performance in all subjects for the fixed time-frequency transform, stimulus parameters, and test materials employed. Yet, trends were evident such that some effect of perturbing cochlear delays could not be ruled out completely.