Suicidal and self-harm behaviour associated with adolescent attention deficit hyperactivity disorder-A study in the Northern Finland Birth Cohort 1986

Background: Suicidal behaviour, i.e. suicidal ideation and suicidal acts, as well as self-harm behaviour, are relatively common among adolescents. Depression and/or female gender seem to be risk factors for suicidal behaviour. However, the role of attention deficit hyperactivity disorder (ADHD) in these behaviours is still unclear. Aim: To study the effect of ADHD on suicidal or self-harm behaviour in adolescents from a general population sample. Methods: The sample was derived from a population-based Northern Finland Birth Cohort 1986 (n = 9432). Based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime Version (Kiddie-SADS-PL) interview performed in a subpopulation (n = 457), the associations between suicidal behaviour and deliberate self-harm (DSH) and the diagnosis of ADHD were studied. Results: Compared with adolescents without ADHD (n = 169), those with ADHD (n = 104) had more suicidal ideation (57% vs. 28%, P < 0.001) and DSH (69% vs. 32%, P < 0.001). In binary logistic models, the effect of ADHD on suicidal ideation remained strong (OR = 6.1) after controlling for several other predictors. Other contributing factors in suicidal behaviour included female gender, childhood emotional and behavioural problems, concurrent depression and anxiety, and, specifically in DSH, behavioural disorder, substance abuse and strains in family relations. Discussion and clinical implications: ADHD is a risk factor for suicidal ideation and DSH. These findings in a general population sample speak for a need to target mental health interventions at children and adolescents with relevant symptoms of ADHD.     

Endogenous nitric oxide and prostaglandin E2 do not regulate the synthesis of each other in interleukin-1β-stimulated rat articular cartilage

Increased levels of nitric oxide (NO) and prostaglandins (PG) are present in the synovial fluid from patients with rheumatoid arthritis and osteoarthritis. Interleukin-1 (IL-1) has been shown to induce the synthesis of both of these mediators. The present work was designed to study the interactions of NO and PGE₂ synthesis induced by IL-1 in rat articular cartilage. Incubation of intact cartilage with IL-1 resulted in different dose response curves for NO and PGE₂ synthesis. Two inhibitors of nitric oxide synthase N-monomethyl-L-arginine (L-NMMA) and L-N-iminoethyl-ornithine, (L-NIO), abolished the IL-1-induced nitrite production but failed to have any influence on the PGE₂ synthesis. Exogenous NO, produced by two chemically different NO-releasing compounds (SIN-1 and GEA 3175) had no effect on PGE₂ synthesis in articular cartilage. Dexamethasone and ketoprofen inhibited IL-1 induced PGE₂ production, while nitrite synthesis remained unaltered. Acetylsalisylic acid (ASA) reduced PGE₂ synthesis and had a slight inhibitory action also on NO production. In conclusion, our results show, that IL-1 induces the synthesis of both PGE₂ and NO in articular cartilage but these two inflammatory mediators are not mediating the synthesis of one another.     

TGFβ inhibits IL-1 -induced iNOS expression and NO production in immortalized chondrocytes

Objective: The balance between anti-inflammatory (e.g. TGFβ) and proinflammatory cytokines (e.g. IL-1 and TNFα), regulates destructive processes in OA cartilage. IL-1 and TNFα enhance nitric oxide (NO) production in OA cartilage through the inducible nitric oxide synthase (iNOS) pathway and NO mediates many of the destructive effects of these cytokines. The aim of the present study was to investigate the effects of TGFβ on NO production in immortalized H4 chondrocytes exposed to IL-1. Results: IL-1 induced NO production in chondrocytes through nuclear factor kappa B (NF-κB) sensitive and dexamethasone insensitive expression of iNOS. TGFβ inhibited IL-1 -induced iNOS expression and NO production in chondrocytes, but it did not have any effect on iNOS mRNA levels. iNOS protein levels were similar in cells treated with IL-1 or IL-1 + TGFβ when measured after 8 h incubation, whereas when measured after 12 h and 24 h incubations, iNOS protein levels were 50% and 80% lower in cells treated with IL-1 + TGFβ than in cells treated with IL-1 alone. Conclusion: TGFβ suppressed IL-1-induced iNOS expression and NO production in chondrocytes, probably by enhancing iNOS protein degradation. This finding suggests an additional mechanism for TGFβ to counteract the destructive effects of IL-1 in OA. Received 24 March 2005; returned for revision 16 June 2005; accepted by J. Hamilton 7 July 2005     

Effects of diclofenac,indomethacin, tolfenamic acid and hydrocortisone on prostanoid production in healthy and rheumatic synovial cells

Prostanoids, found in enhanced concentrations in rheumatic synovial fluid, are involved in the joint destruction seen in rheumatoid arthritis. Adherent cells isolated from rheumatic synovia produce higher amounts of prostanoids in a primary cell culture than cells originating from non-inflamed synovia. In the present study, it was found that exogenous arachidonic acid diminished the differences in prostanoid production between healthy and rheumatic synovial cells. Non-steroidal anti-inflammatory analgesics in clinically relevant concentrations had similar inhibitory effects on arachidonic acid-stimulated prostanoid synthesis in both healthy and rheumatic cells. In the presence of exogenous arachidonic acid, hydrocortisone (0.3–5.0 M) did not affect prostanoid production in healthy cells. In rheumatic synovial cells hydrocortisone reduced PGE₂ and PGF₂ synthesis to about half of the control value and the effect was not reversed by adding excess exogenous arachidonic acid. Altered regulation of phospholipase A₂ activity in rheumatic synovia could explain the observed differences between healthy and rheumatic synovial cells.     

Expression and regulation of collagenase-2 (MMP-8) in head and neck squamous cell carcinomas

MMP-8 (collagenase-2) is the most effective collagenase to initiate type I collagen degradation. Since initiation of lysis of the surrounding collagen matrix is an essential prerequisite for carcinoma cells to spread, this study investigated the expression of MMP-8 in squamous cell carcinoma (SCC) of the head and neck in vivo and in vitro. Most of the recently established head and neck carcinoma cell lines (22/25), corresponding tumour (5/7) and dermal (2/2) fibroblasts, commercial tongue carcinoma (HSC-3 and SCC-25), and transformed keratinocyte cell lines of the tongue (IHGK) and skin (HaCaT) expressed MMP-8 mRNA analysed by the PCR method. Western blotting revealed a latent 50 kD band in concentrated culture media of carcinoma cells and corresponding tumour and dermal fibroblasts. The expression of immunoreactive MMP-8 protein was reduced 30% by transforming growth factor beta-1 (TGF-beta1) at 1 ng/ml concentration and 60% at 10 ng/ml concentration, but up-regulated 2- and 2.5-fold after 10 nM and 100 nM phorbol 12-myristate 13 acetate (PMA), respectively. Immunohistological staining localized MMP-8 protein in a few malignant invading tumour cell islands, certain fibroblasts, polymorphonuclear neutrophils (PMNs), and plasma cells. In situ hybridization revealed a faint sporadic signal in carcinoma cells of all eight tissue sections analysed. It is concluded that tissue from head and neck carcinomas can express MMP-8 both in vivo and in vitro. Since the amount of MMP-8 in carcinoma and stromal cells is rather low, MMP-8 may have a potential role, with other collagenases, in the proteolysis of connective tissue associated with the spreading of invasive carcinoma.     

Serum and follicular fluid leptin during in vitro fertilization: relationship among leptin increase, body fat mass, and reduced ovarian response.

The satiety factor leptin is expressed in several reproductive tissues, but its role in the control of reproductive physiology is not well understood. We studied leptin concentrations in the sera and follicle fluids of 52 women [body fat mass percentage (BFM%) range, 19.6-38.8%] undergoing pituitary down-regulation and ovarian hyperstimulation for in vitro fertilization (IVF) treatment. Fasting serum samples were collected 1) at maximal suppression before the initiation of gonadotropin treatment, 2) at maximal ovarian hyperstimulation, 3) at the time of oocyte retrieval, and 4) 16 days later when all subjects were under exogenous luteal support using 600 mg progesterone daily. Follicular fluid (FF) was obtained at oocyte retrieval from two representative preovulatory follicles in both ovaries. During ovarian hyperstimulation there was a significant 60% increase in serum leptin concentrations from 10.9 +/- 1.1 (SEM) to 15.7 +/- 1.5 ng/mL (P < 0.01) between suppression and maximal hyperstimulation, demonstrating that the ovarian functional state can affect serum leptin concentrations. A serum leptin increase of 22-198% during ovarian hyperstimulation was evident in 43 subjects, whereas in 9, leptin concentrations remained unchanged. A positive correlation between leptin change and BFM% (r = 0.55; P < 0.0005) was observed in the 43 leptin responders. The follicular fluid leptin level was similar to that in serum. In separate linear regression analysis, BFM% contributed to 59-64%, body mass index to 46-56%, and weight to 46-55% (all P < 0.001) of the variability in leptin concentrations at the 4 time points. The 20-fold increase in serum estradiol concentrations during IVF was not significantly correlated with changes in leptin concentrations. On the contrary, the relative serum leptin increase was negatively associated with the ovarian response to hyperstimulation, as revealed by the numbers of follicles (b = -0.28; r2 = 8.1%; P < 0.05) and oocytes retrieved (b = -0.39; r2 = 15.2%; P < 0.01). This relationship was further reflected in a positive correlation between the percent increases in leptin and FSH concentrations (r = 0.39; P < 0.01). The significant relationship of high leptin and reduced ovarian response was also maintained when the cumulative dose of FSH was used as a covariable. Reduced ovarian response was not a function of body mass index, BFM%, basal leptin levels, or insulin concentrations. Fasting serum insulin concentrations remained unchanged in response to IVF, but were positively correlated to serum leptin concentrations at all four time points. Our data suggest that leptin production may be influenced by the ovarian functional state. During IVF a high relative leptin increase is associated with adiposity and a reduced ovarian response. These observations support the possibility that high leptin concentrations might reduce ovarian responsiveness to gonadotropins. Hence, leptin might explain in part why obese individuals require higher amounts of gonadotropins than lean subjects to achieve ovarian hyperstimulation.     

FTIR spectroscopy and strengthening behavior of liquid crystalline oligomers of 2‐alkoxy‐4‐hydroxybenzoic acids and 4‐hydroxybenzoic acid

A series of liquid crystalline oligomers of 4‐hydroxybenzoic acid (HBA) and 2‐alkoxyHBAs were synthesized. The structural and conformational changes of the oligomers were studied by FTIR spectroscopy. The strengthening abilities of the synthesized co‐oligomers were investigated by blending the oligomers with polyamide 11 (PA 11).