Alpha-melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation.

Alpha-Melanocyte-stimulating hormone (MSH) is a potent anti-inflammatory agent in many models of inflammation, suggesting that it inhibits a critical step common to different forms of inflammation. We showed previously that alpha-MSH inhibits nitric oxide (NO) production in cultured macro-phages. To determine how alpha-MSH acts in vivo, we induced acute hepatic inflammation by administering endotoxin (LPS) to mice pretreated with Corynebacterium parvum, alpha-MSH prevented liver inflammation even when given 30 min after LPS administration. To determine the mechanisms of action of alpha-MSH, we tested its influence on NO, infiltrating inflammatory cells, cytokines, and chemokines. Alpha-MSH inhibited systemic NO production, hepatic neutrophil infiltration, and increased hepatic mRNA abundance for TNF alpha, and the neutrophil and monocyte chemokines (KC/IL-8 and MCP-1). We conclude that alpha-MSH prevents LPS-induced hepatic inflammation by inhibiting production of chemoattractant chemokines which then modulate infiltration of inflammatory cells. Thus, alpha-MSH has an effect very early in the inflammatory cascade.     

Extracorporeal Photopheresis for the Treatment of Cutaneous T-Cell Lymphoma

Journal of Cutaneous Medicine and Surgery -     

Interleukin-1 stimulates human uterine prostaglandin production through induction of cyclooxygenase-2 expression

PROBLEM: Uterine infection occurs in as much as 20% of preterm labor and results in increased decidual cytokines. The objective of this study was to examine the effect of interleukin-1 (IL-1) and the cyclooxygenase-2 (COX-2) inhibitor, NS-398, on myometrial prostaglandin (PG) production and COX-2 expression. METHOD OF STUDY: Human uterine myocytes were stimulated with IL-1 (0-50 ng/mL) over 24 hr. PGE2, PGF2alpha, and 6-keto F1alpha were measured by enzyme-linked immunosorbent assay. Both COX-1 and COX-2 proteins and mRNA were measured by western and northern blot, respectively. RESULTS: IL-1 increased PG production beginning at 6 hr, COX-2 protein increased beginning at 4 hr and continued to increase at 24 hr. COX-2 mRNA increased at 2 hr and peaked at 4 hr. NS-398 blocked PG production but had no effect on COX-2 protein or mRNA. CONCLUSIONS: IL-1 increases PG production by myometrium by increased COX-2 expression. NS-398 completely blocks IL-1-induced PG production. With intrauterine infection, IL-1 may induce labor through the autocrine production of uterotonic PGs.     

Surgical Treatment and Proposed Modified Classification for Harrington Class III Periacetabular Metastases

ObjectivesThis study aims to: (i) evaluate the outcome of patients with Harrington class III lesions who were treated according to Harrington classification; (ii) propose a modified surgical classification for Harrington class III lesions; and (iii) assess the efficiency of the proposed modified classification.MethodsThis study composes two phases. During phase 1 (2006 to 2011), the clinical data of 16 patients with Harrington class III lesions who were treated by intralesional excision followed by reconstruction of antegrade/retrograde Steinmann pins/screws with cemented total hip arthroplasty (Harrington/modified Harrington procedure) were retrospectively reviewed and further analyzed synthetically to design a modified surgical classification system. In phase 2 (2013 to 2019), 62 patients with Harrington class III lesions were classified and surgically treated according to our modified classification. Functional outcome was assessed using the Musculoskeletal Tumor Society (MSTS) 93 scoring system. The outcome of local control was described using 2‐year recurrence‐free survival (RFS). Owing to the limited sample size, we considered P < 0.1 as significant.ResultsIn phase 1, the mean surgical time was 273.1 (180 to 390) min and the mean intraoperative hemorrhage was 2425.0 (400.0 to 8000.0) mL, respectively. The mean follow‐up time was 18.5 (2 to 54) months. Recurrence was found in 4 patients and the 2‐year RFS rate was 62.4% (95% confidence interval [CI] 31.6% to 93.2%). The mean postoperative MSTS93 score was 56.5% (20% to 90%). Based on the periacetabular bone destruction, we categorized the lesions into two subgroups: with the bone destruction distal to or around the inferior border of the sacroiliac joint (IIIa) and the bone destruction extended proximal to inferior border of the sacroiliac joint (IIIb). Six patients with IIIb lesions had significant prolonged surgical time (313.3 vs 249.0 min, P = 0.022), massive intraoperative hemorrhage (3533.3 vs 1760.0 mL, P = 0.093), poor functional outcome (46.7% vs 62.3%, P = 0.093), and unfavorable local control (31.3% vs 80.0%, P = 0.037) compared to the 10 patients with IIIa lesions. We then modified the surgical strategy for two subgroup of class III lesions: Harrington/modified Harrington procedure for IIIa lesions and en bloc resection followed by modular hemipelvic endoprosthesis replacement for IIIb lesions. Using the proposed modified surgical classification, 62 patients in the phase 2 study demonstrated improved surgical time (245.3 min, P = 0.086), intraoperative hemorrhage (1466.0 mL, P = 0.092), postoperative MSTS 93 scores (65.3%, P = 0.067), and 2‐year RFS rate (91.3%, P = 0.002) during a mean follow‐up time of 19.9 (1 to 60) months compared to those in the phase 1 study.ConclusionThe Harrington surgical classification is insufficient for class III lesions. We proposed modification of the classification for Harrington class III lesions by adding two subgroups and corresponding surgical strategies according to the involvement of bone destruction. Our proposed modified classification showed significant improvement in functional outcome and local control, along with acceptable surgical complexity in surgical management for Harrington class III lesions.     

Human prostatic-carcinoma cells modulate lymphocyte-proliferation by an immunosuppressive activity

We have identified an immunosuppressive activity from the conditioned medium of an androgen-independent human prostatic carcinoma cell line, JCA-1. This activity is constitutively produced by JCA-1 cells and is capable of suppressing normal human peripheral blood lymphocyte proliferation irreversibly in a dose-dependent manner. Immunosuppressive activity was semi-purified by a combination of ion-exchange chromatography and gel filtration with an apparent molecular weight of 40-55 kDa. The immunosuppressive activity was not cytolytic to lymphocytes and was sensitive to 56 degrees C, reducing agent as well as to protease digestion. Cell cycle analysis revealed that the suppressive activity did not induce apoptosis, but it prevented some G(1) lymphocytes from entering into the S phase of the cell cycle.     

Effects of Supraphysiological Testosterone Treatment and Orchiectomy on Ischemia/Reperfusion‐Induced Bladder Dysfunction in Male Rabbits

IntroductionThe roles of testosterone and orchiectomy on male bladder subjected to ischemic/reperfusion (I/R) injuries received little attention. To fill this gap, the present study intended to examine testosterone and orchiectomy effects on male rabbits subjected to I/R damages.AimTo elucidate the effects of testosterone and orchiectomy on contractile response, bladder morphology, interstitial fibrosis, and oxidative stress in male rabbit bladder subjected to I/R surgery.MethodsMale New Zealand rabbits were distributed into five groups as follows: Group 1 received sham surgical procedure. In group 2, I/R surgery was performed. In group 3, testosterone (100 μg/kg/day) was intramuscularly injected prior to I/R surgery. In group 4, orchiectomy was performed prior to I/R surgery. In group 5, orchiectomy was performed with subsequent testosterone administration, followed by I/R surgery. All the rabbits were euthanized 7 days after I/R. Comparative studies were analyzed to elucidate the effects of testosterone and orchiectomy on bladder dysfunction subjected to I/R injuries.Main Outcome MeasuresBladder contractile function was evaluated. Masson's trichrome staining and immunohistochemical studies were performed to evaluate bladder morphology and intramural nerve terminals. Western blotting was examined to investigate the expressions of fibrosis and oxidative stress markers.ResultsI/R surgery significantly decreased bladder contractility in response to various stimulations with and without testosterone treatment. I/R damages decreased bladder nerve density with and without testosterone. The expressions of fibrosis and oxidative stress‐related proteins were increased by I/R injuries with or without testosterone treatment. Testosterone depletion significantly decreased the expressions of transforming growth factor‐β and fibronectin expressions after I/R injury. Supraphysiological testosterone treatment after orchiectomy greatly increased the expressions of these fibrosis proteins; however, orchiectomy alone ameliorated I/R injuries.ConclusionsTestosterone treatment or orchiectomy affected I/R‐induced bladder damages in male rabbits. Orchiectomy decreased the level of fibrosis and oxidative stress markers and increased neurofilament densities. Supraphysiological exogenous testosterone administration after orchiectomy further exacerbated such detrimental effects of I/R.     

Adolescent Internet use and its relationship to cigarette smoking and alcohol use: A prospective cohort study

The present study aims to investigate the longitudinal impact of situational Internet use on future cigarette smoking and alcohol use among male and female adolescents. A Northern Taiwanese cohort sample of adolescents with no prior use of cigarettes (n = 1445) or alcohol (n = 1468) was surveyed at age 16 and again 4 years later. Information regarding where, why, and length of time spent using the Internet was gathered from the 16-year-old participants. Outcome information regarding cigarette/alcohol use was gathered via a follow-up questionnaire at age 20. Multivariate regressions were used to incorporate peer, individual and family characteristics as measured at age 16 and create models of future cigarette and alcohol use at age 20. The analyses demonstrated that adolescent Internet use, particularly where such use took place, has a significant impact on future cigarette smoking and alcohol use, adjusted for conventional factors, and its relationship differs significantly by gender. Female adolescents with Internet café use appear to be especially likely to develop these two risky behaviors. The why of Internet use is also a predictor of future cigarette smoking. Finally, time spent using the Internet is significantly related to alcohol use; greater use of the Internet is associated with higher levels of drinking. The results revealed that different risky behaviors are differentially influenced by separate components of adolescent Internet use. These findings suggest that programs aimed at promoting adolescent health could potentially benefit Taiwanese adolescents by including components related to situational Internet use and taking gender into consideration.