Development of an in vitro burn wound model

Healing of a deeper burn wound is a complex process that often leads to scar formation. Skin wound model systems are important for the development of treatments preventing scarring. The aim of this study is to develop a standardized in vitro burn wound model that resembles the in vivo situation. A burn wound (10 × 2 mm) was made in ex vivo skin and the skin samples were cultured at the air–liquid interface for 7, 14, and 21 days. Cells in the skin biopsies maintained their viability during the 21-day culture period. During culture, reepithelialization of the wound took place from the surrounding tissue and fibroblasts migrated into the wound area. Cells of the epithelial tongue and fibroblasts near the wound margin were proliferating. During culture, skin-derived antileukoproteinase and keratin 17 were expressed only in the epithelial tongue. Both collagen type IV and laminin were present underneath the newly formed epidermis, indicating that the basement membrane was restored. These results show that the burn wound model has many similarities to in vivo wound healing. This burn wound model may be useful to study different aspects of wound healing and testing pharmaceuticals and cosmetics on, e.g., migration and reepithelialization.     

Temporomandibular joint arthrography following surgical treatment of internal derangements

Arthrograms of the temporomandibular joint were obtained in 20 symptomatic joints that had previous reconstructive arthroplasty with disk repositioning because of internal derangements. Preoperative arthrograms were available for comparison in 18 joints. Symptoms resulting in a postoperative arthrogram included pain, limited ability to open the mouth, and clicking of the joints. Postoperative arthrographic findings included limited anterior translation of the condyle (90%), irregularity in outline of the intraarticular contrast agent (60%), a conical configuration of the posterior recess (25%), decreased size of the joint (28%), anterior displacement of the meniscus (25%), and perforated meniscus (15%). Many of these findings may have resulted from fibrosis and scarring, which may be a response to intraarticular bleeding. The mechanism by which the fibrosis causes the postsurgical arthrographic features is discussed.     

Altered behavioral response to dopamine D3 receptor agonists 7-OH-DPAT and PD 128907 following repetitive amphetamine administration.

Behavioral sensitization, the progressive and enduring enhancement of certain behaviors following repetitive drug use, is mediated in part by dopaminergic pathways. Increased locomotor response to drug treatment, a sensitizable behavior, is modulated by an opposing balance of dopamine receptor subtypes, with D1/D2 dopamine receptor stimulation increasing and D3 dopamine receptor activation inhibiting amphetamine-induced locomotion. We hypothesize that tolerance of D3 receptor locomotor inhibition contributes to behavioral sensitization. In order to test the hypothesis that expression of behavioral sensitization results in part from release of D3 receptor-mediated inhibition, thereby resulting in decreased response to D3 receptor agonists, we examined the effect of repetitive amphetamine administration on the behavioral response to the D3 receptor preferring agonists 7-OH-DPAT and PD 128907. D3-selective effects have recently been described for both drugs at a low dose. At 1 week following completion of a repetitive treatment regimen, amphetamine-pretreated rats displayed a decreased response to D3-selective doses of both 7-OH-DPAT and PD 128907, when compared to animals receiving saline pretreatment. Moreover, in addition to the quantitative alteration in response, there was a change in the inter-relation between response to amphetamine and D3 agonist. A highly significant inverse relation between locomotor inhibitory response to PD 128907 and the locomotor-stimulant response to amphetamine was observed prior to amphetamine treatment. In contrast, 10 days following repetitive amphetamine treatment, the relation between response to PD 128907 and amphetamine was not detected. The observed behavioral alteration could not be accounted for by changes in D3 receptor binding in ventral striatum. These findings suggest a persistent release of D3 receptor-mediated inhibitory influence contributes to the expression of behavioral sensitization to amphetamine.     

Quality of life (QOL) assessment of MIP (mitomycin, ifosfamide and cisplatin) chemotherapy in advanced non-small cell lung cancers (NSCLC)

BACKGROUND: Quality of life (QOL) assessment has emerged to measure and quantify the balance between treatment benefit and toxicity, and has a value in predicting response and overall survival in cancer patients. METHODS: From July 1995 to February 1997, 38 symptomatic patients with advanced non-small cell lung cancer (NSCLC) were treated with MIP chemotherapy (mitomycin 6 mg/m2, ifosfamide 3000 mg/m2 and cisplatin 50 mg/m2 on day 1 every 3 weeks). Patients were assessed for QOL including physical well-being, general symptoms and lung cancer-specific symptoms, as well as objective response. RESULTS: The overall response rate was 38.9% (14/36, all were partial response) and the median duration of response was 3.5 months [95% confidence interval (CI) 2.0-4.0]. The median duration of overall survival was 7 months (95% CI 5.9-8.5). The overall improvement of QOL was 58.3% with 21 patients feeling better on treatment. The toxicity of chemotherapy was mild, mainly nausea/vomiting and minimal alopecia. Using multiple clinical predictors of survival (age, histology, stage, performance status), only change of QOL emerged significantly (P = 0.0007). CONCLUSIONS: MIP had an endurable response and low toxicity profile, and provided good QOL. Integral QOL data in our study provided the strong prediction of survival in advanced NSCLC. Further experienced QOL study will provide greatly enhanced outcome data in clinical trials.      

Sexual behavior and sex-associated environmental cues activate the mesolimbic system in male rats.

The mesolimbic system plays an important role in the regulation of both pathological behaviors such as drug addiction and normal motivated behaviors such as sexual behavior. The present study investigated the mechanism by which this system is endogenously activated during sexual behavior. Specifically, the effects of sexual experience and sex-related environmental cues on the activation of several components of the mesolimbic system were studied. The mesolimbic system consists of a dopaminergic projection from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). Previous studies suggest that these neurons are under tonic inhibition by local GABA interneurons, which are in turn modulated by mu opioid receptor (MOR) ligands. To test the hypothesis that opioids are acting in the VTA during sexual behavior, visualization of MOR internalization in VTA was used as a marker for ligand-induced activation of the receptor. Significant increases in MOR internalization were observed following copulation or exposure to sex-related environmental cues. The next goal was to determine if sexual behavior activates dopamine neurons in the VTA, using tyrosine hydroxylase as a marker for dopaminergic neurons and Fos-immunoreactivity as a marker for neuronal activation. Significant increases in the percentage of activated dopaminergic neurons were observed following copulation or exposure to sex-related environmental cues. In addition, mating and sex-related cues activated a large population of nondopaminergic neurons in VTA as well as neurons in both the NAc Core and Shell. Taken together, our results provide functional neuroanatomical evidence that the mesolimbic system is activated by both sexual behavior and exposure to sex-related environmental cues.     

Diffusion‐prepared stimulated‐echo turbo spin echo (DPsti‐TSE): An eddy current‐insensitive sequence for three‐dimensional high‐resolution and undistorted diffusion‐weighted imaging

In this study, we present a new three‐dimensional (3D), diffusion‐prepared turbo spin echo sequence based on a stimulated‐echo read‐out (DPsti‐TSE) enabling high‐resolution and undistorted diffusion‐weighted imaging (DWI). A dephasing gradient in the diffusion preparation module and rephasing gradients in the turbo spin echo module create stimulated echoes, which prevent signal loss caused by eddy currents. Near to perfect agreement of apparent diffusion coefficient (ADC) values between DPsti‐TSE and diffusion‐weighted echo planar imaging (DW‐EPI) was demonstrated in both phantom transient signal experiments and phantom imaging experiments. High‐resolution and undistorted DPsti‐TSE was demonstrated in vivo in prostate and carotid vessel wall. 3D whole‐prostate DWI was achieved with four b values in only 6 min. Undistorted ADC maps of the prostate peripheral zone were obtained at low and high imaging resolutions with no change in mean ADC values [(1.60 ± 0.10) × 10^?3 versus (1.60 ± 0.02) × 10^?3 mm²/s]. High‐resolution 3D DWI of the carotid vessel wall was achieved in 12 min, with consistent ADC values [(1.40 ± 0.23) × 10^?3 mm²/s] across different subjects, as well as slice locations through the imaging volume. This study shows that DPsti‐TSE can serve as a robust 3D diffusion‐weighted sequence and is an attractive alternative to the traditional two‐dimensional DW‐EPI approaches.     

Parallel declines in Fos activation of the medial anteroventral periventricular nucleus and LHRH neurons in middle-aged rats

The middle-age decline in reproductive function is manifested by reduced LHRH release, resulting in a decreased magnitude and delay of onset of the LH surge. Earlier studies suggested that the reductions in LHRH neural activation in middle-aged rats resulted from deficits in the afferent drive to the LHRH neurons. One critical afferent to the LHRH neurons lies in the anteroventral periventricular preoptic area (AVPv) nucleus. The neurons of the medial AVPv are synchronously activated to express Fos with LHRH neurons at the time of an LH surge in young adult animals. The present study examined whether, in middle age, reductions in the activation of AVPv neurons accompany the reduction in Fos activation in LHRH neurons. Young (3- to 4-month-old) and middle-aged (10- to 12-month-old) spontaneously cycling and ovariectomized steroid-replaced rats were killed during peak and early descending phase of the LH surge, and their brains were examined for Fos in LHRH and AVPv neurons. Young animals had a characteristic increase in Fos expression in both LHRH and AVPv neurons. In middle-aged rats, the proportion of LHRH neurons expressing Fos at the time of an LH surge was reduced by approximately 50%, irrespective of whether surges were spontaneous or induced by exogenous steroids. A similar reduction in the number of Fos+ cells (by approximately 50%) was noted in the medial AVPv. Linear regression analysis of the relationship between the extent of Fos activation in LHRH and AVPv neurons revealed a strong positive correlation (r(2) = 0.66; P < 0.01), suggesting that changes in the AVPv's drive to LHRH neurons underlie the decrease in LHRH activity in middle age. A second series of experiments examined whether decreased input from the AVPv could account for reduced Fos activation in LHRH neurons seen in middle-aged animals. When the medial AVPv was lesioned, LHRH neurons failed to express Fos on the side ipsilateral to the lesion. Animals with lesioned medial AVPv also had significantly lower LH values than animals with an intact medial AVPv. Taken together, these data suggest that a principal deficit in middle-aged rats is the ability of the medial AVPv to stimulate LHRH neurons.