How contexts promote and prevent relapse to drug seeking.

The contexts where drugs are self-administered play an important role in regulating persistent drug taking and in relapse to such taking after periods of abstinence. Here, we review the behavioral and brain mechanisms enabling contexts to promote and prevent relapse to drug seeking. We review the key brain structures, their neuropharmacology and their connectivity. We discuss the similarities and differences between the mechanisms for context-induced reinstatement of drug seeking vs. other forms of relapse to drug seeking in animal models and we highlight the numerous deficits in our understanding. We emphasize that current understanding, although significant, defies explanations in terms of models at the level of brain structures and their connectivity. Rather, we show that there is significant functional compartmentalization and segregation within these structures during reinstatement and extinction of drug seeking that parallels their anatomical segregation into circuits and channels. A key challenge is to recognize this complexity, understand how these circuits and channels are organized, as well as understand how different modes of activity of ensembles of neurons within them promote abstinence or relapse to drug seeking.

Racial, ethnic, and cultural differences in dementia caregiving: review and analysis.

This study provides a review and analysis of the empirical research published since 1985 that has examined the impact of race, culture, and/or ethnicity on the dementia caregiving experience. Ten of the 12 studies included in the review focused on comparisons between Black and White caregivers; one examined differences between Black and Hispanic caregivers, and one focused on White and Hispanic caregivers. Compared to White caregivers, non-White caregivers: a) were less likely to be a spouse and more likely to be an adult child, friend, or other family member, b) reported lower levels of caregiver stress, burden, and depression, c) endorsed more strongly held beliefs about filial support, and d) were more likely to use prayer, faith, or religion as coping mechanisms. Strategies for advancing research in this area are discussed.

Morphogenesis during asexual reproduction in Pygospio elegans Claparede (Annelida, Polychaeta).

The spionid Pygospio elegans reproduces both asexually and sexually. Using scanning electron and bright field microscopy, we examined morphogenesis following asexual reproduction to determine how "lost" body regions were regenerated after a worm spontaneously divided. Asexual reproduction occurred through transverse fission and divided the parent worm into 2 to 6 fragments (architomy). All fragments retained their original anterior-posterior polarity. Regeneration in all fragments followed a specific series of events: wound healing (day 1); extension of the blastema to generate lost body regions-specifically, the head and thorax for posterior fragments and the tail and pygidium for anterior fragments (days 2-3); segmentation (days 3-6); and differentiation of segment- or region-specific structures (days 4-8). This pattern occurred regardless of where the original division took place. Subsequent growth occurred through addition of terminal setigers anterior to the pygidium followed by differentiation of tail setigers into abdominal setigers, leaving the tail region about 6 to 10 setigers in size. Division rates were compared in worms from three populations in Nova Scotia, Canada. Worms from two populations (Conrad's Beach, Starr's Point) divided more frequently (about 1.2 and 1.3 weeks between divisions, respectively) than worms from Bon Portage Island (3.5 weeks between divisions). Fragments containing the original head (original mouth intact, generally much larger fragment) had a higher survivorship than fragments containing the original tail.

Transplantation of porous tubes following spinal cord transection improves hindlimb function in the rat.

STUDY DESIGN: Experimental. OBJECTIVE: To determine the effects of a porous tube transplant in spinal cord transected rats. SETTING: Acadia University, Wolfville, Nova Scotia, Canada. METHODS: Female rats were randomly assigned to three experimental groups: control (Con, n=8), spinal cord transected (Tx, n=5) and spinal cord transected with transplant (TxTp, n=7). The rats in the TxTp and Tx groups received a complete spinal cord transection at the T10 level and the TxTp group immediately received a porous tube transplant. RESULTS: Locomotor activity rated on the Basso, Beattie, Bresnahan scale improved significantly in the TxTp animals over the 4 weeks such that final scores were 21, 1.4 and 7.1 for the Con, Tx and TxTp groups, respectively. As expected, the muscle to body mass ratios of the hindlimb skeletal muscles of the Tx group were decreased (soleus 35%, plantaris 29% and gastrocnemius 29%) and this was also observed in the TxTp group (soleus 33%, plantaris 23% and gastrocnemius 30%). Cytochrome c oxidase (CYTOX) activity in the plantaris was decreased by Tx but maintained in the TxTp group (Con=82.2, Tx=44.8 and TxTp=72.8 U/min/g). CONCLUSION: Four weeks after the spinal cord transection, plantaris CYTOX activity and locomotor function improved with porous tube implantation. SPONSORSHIP: Natural Sciences and Engineering Research Council.

A Metamorphic Inducer in the Opisthobranch Haminaea callidegenita: Partial Purification and Biological Activity.

Larvae of Haminaea callidegenita (Mollusca: Cephalaspidea) were induced to metamorphose by a compound found in the gelatinous matrix composing most of the egg mass. A functionally similar compound isolated from adult tissue also induced metamorphosis in H. callidegenita larvae. Opisthobranchs are frequently induced to metamorphose by a specific prey item or a substrate characteristic of the adult habitat, but this is the first known instance of metamorphosis occurring in response to a compound produced by adult conspecifics. The inducer was purified from egg mass jelly (EMJ) by high pressure liquid chromatography (HPLC) and was found to be smaller than 1000 Da, polar, non-proteinaceous, and very stable. We isolated a compound of identical activity from egg masses produced by four other opisthobranch species, suggesting that the same or chemically similar compounds are intrinsic to opisthobranch egg masses. However, only H. callidegenita larvae metamorphosed in response to EMJ. Competent larvae of five other mollusc species did not respond to the partially purified EMJ inducer but did respond to a specific substrate associated with each species. The presence of the inducer within the egg mass causes an unusual developmental pattern in H. callidegenita, a poecilogonous species that produces both swimming veliger and crawling juvenile offspring.

Potentiated lymphokine-activated killer cell activity generated by low-dose interleukin-2 and mismatched double-stranded RNA.

Lymphokine-activated killer (LAK) cell activity was measured in human peripheral blood mononuclear cells (PBMC) treated in vitro for 3 days with recombinant interleukin-2 (rIL-2) and mismatched double-stranded RNA (dsRNA). Lytic activity was measured utilizing K562 (NK-sensitive) and 786-0 (NK-resistant) target cells. PBMC cultured with rIL-2 (10-1000 BRMP U/ml) alone showed concentration-dependent lytic activity against the 786-0 target cells, while cells cultured in unsupplemented medium or medium supplemented with mismatched dsRNA (200 micrograms/ml) alone could not lyse the 786-0 targets. The combination of mismatched dsRNA with suboptimal concentrations of rIL-2 (10-30 U/ml) showed enhancement of both natural killer (NK) and LAK cell activities. The uptake of [3H]thymidine by treated effector cells was dependent on time and rIL-2 concentration and was not increased in the cells treated with low-dose rIL-2/mismatched dsRNA, compared to those treated with low-dose rIL-2 or mismatched dsRNA alone. Similarly, changes in the expression of CD3, CD4, CD8, CD57, CD16 and CD25 cell surface antigens were independent or rIL-2 concentration and not altered by the presence of mismatched dsRNA. These results indicate that mismatched dsRNA can potentiate rIL-2-induced LAK cell activity by increasing the functional activity per cell, rather than by increasing the number of activated cells.

Antitumor effects of interleukin-2 and mismatched double-stranded RNA, individually and in combination, against a human malignant melanoma xenograft.

The antitumor effects of recombinant interleukin-2 (rIL-2) and mismatched double-stranded RNA (dsRNA) were assessed in tissue culture and in a nude mouse model. Mismatched dsRNA did not show a direct antiproliferative effect against the human malignant melanoma cell line, BRO, in tissue culture. However, treatment of the BRO cells with up to 1000 units/ml rIL-2 in culture showed a slight increase in growth rate. Combined rIL-2/mismatched dsRNA treatment also demonstrated a similar slight enhancement of growth. Nude mice bearing subcutaneous tumors were treated by intraperitoneal injection of low doses (5000-20,000 units) of rIL-2 and mismatched dsRNA (500 micrograms). The in vivo tumor growth was significantly inhibited by the combined treatments (P less than 0.05) and survival was significantly increased (P less than 0.05). Measurement of cytotoxicity using splenocytes from treated animals showed significant augmentation of lytic activity against natural killer (NK)-sensitive YAC-1 cells in all rIL-2/mismatched dsRNA treatment groups, compared to the individual treatments or controls (P less than 0.05). Cytotoxicity of the splenocytes against the NK-resistant BRO cells was also augmented in animals treated with mismatched dsRNA and the highest rIL-2 dose utilized here (P less than 0.01). Renal, liver, and hematological toxicity was evaluated by measurement of blood urea nitrogen, creatinine, serum asparrtate aminotransferase, and a complete blood count with differential. There were no significant differences in these parameters in any of the treatment groups. Similarly, no differences in weight of the animals was seen in any treatment group. These results indicate that the combination of low-dose rIL-2 and mismatched dsRNA can potentiate host-mediated antitumor effects, yielding increased survival, without significant toxicity.