Gingival crevicular fluid levels of MMP-8, MMP-9, TIMP-2, and MPO decrease after periodontal therapy

P>Background This study aimed at comparing the levels of matrix metalloproteinase (MMP)-8, tissue Inhibitor of MMPs (TIMP)-1 and TIMP-2, Myeloperoxidase (MPO), and MMP-9 in the gingival crevicular fluid (GCF) of chronic periodontitis (CP) patients and controls at baseline and 3 months after non-surgical therapy. Materials and Methods GCF was collected from one site of 15 control subjects and 27 CP patients. MMP-8, MMP-9, TIMP-1, and TIMP-2 were determined by Enzyme-linked immunoabsorbent assay; different forms of MMP-9, by gelatin zymography; and MPO, colorimetrically. Results At baseline, higher levels of MMP-8, TIMP-2, MPO, and the 87 kDa-MMP-9 were found in patients compared with controls (p < 0.001), and these molecules decreased after therapy (p < 0.03). There were no differences between the groups with respect to the higher molecular forms of MMP-9 (180, 130, 92 kDa) or total MMP-9 at baseline. No differences were observed in TIMP-1 levels. In controls, decreased levels of TIMP-2 and the higher molecular forms of MMP-9 (180, 130, 92 kDa) were found 3 months after therapy compared with baseline (p < 0.01). Conclusions Higher levels of MMP-8, TIMP-2, MPO, and 87 kDa MMP-9 were found in the GCF of patients compared with controls, and these markers decreased 3 months after periodontal therapy.

A genetic polymorphism of matrix metalloproteinase 9 (MMP-9) affects the changes in circulating MMP-9 levels induced by highly active antiretroviral therapy in HIV patients

We examined whether two functional polymorphisms (g.-1562C>T and g.-90(CA)14-24) in the matrix metalloproteinase (MMP)-9 gene or MMP-9 haplotypes affect the circulating levels of pro-MMP-9 and pro-MMP-9/TIMP-1 (tissue inhibitor of metalloproteinase-1) ratios in AIDS patients, and modulate alterations in these biomarkers after highly active antiretroviral therapy (HAART). We studied 82 patients commencing HAART. Higher pro-MMP-9 concentrations and pro-MMP-9/TIMP-1 ratios were found in CT/TT patients compared with CC patients. HAART decreased pro-MMP-9 levels and pro-MMP-9/TIMP-1 ratios in CT/TT patients, it did not modify pro-MMP-9 levels and it increased pro-MMP-9/TIMP-1 ratios in CC patients. The g.-90(CA)14-24 polymorphism, however, produced no significant effects. Moreover, we found no significant differences in HAART-induced changes in plasma pro-MMP-9, TIMP-1 and pro-MMP-9/TIMP-1 ratios when different MMP-9 haplotypes were compared. These findings suggest that the g.-1562C>T polymorphism affects pro-MMP-9 levels in patients with AIDS and modulates the alterations in pro-MMP-9 levels caused by HAART, thus possibly affecting the risk of cardiovascular complications. The Pharmacogenomics Journal (2009) 9, 265-273; doi: 10.1038/tpj.2009.13; published online 21 April 2009

Low Intensity Laser Therapy in Temporomandibular Disorder: a Phase II Double-Blind Study

The purpose of this study was to evaluate the analgesic effect of Low Intensity Laser Therapy (LILT) and its influence on masticatory efficiency in patients with temporomandibular dysfunction (TMD). This study was performed using a random, placebo-controlled, and double-blind research design. Fourteen patients were selected and divided into two groups (active and placebo). Infrared laser (780 nm, 70 mw, 60s, 105J/cm(2)) was applied precisely and continuously into five points of the temporomandibular joint (TMJ) area: lateral point (LP), superior point (SP), anterior point (AP), posterior point (PP), and posterior-inferior point (PIP) of the condylar position. This was performed twice per week, for a total of eight sessions, To ensure a double-blind study, two identical probes supplied by the manufacturer were used: one for the active laser and one for the inactive placebo laser. They were marked with different letters (A and B) by a clinician who did not perform the applications. A Visual Analogue Scale (VAS) and a colorimetric capsule method were employed. Data were obtained three times: before treatment (Ev1), shortly after the eighth session (Ev2), and 30 days after the first application (Ev3). Statistical tests revealed significant differences at one percent (1%) likelihood, which implies that superiority of the active group offered considerable TMJ pain improvement. Both groups presented similar masticatory behavior, and no statistical differences were found. With regard to the evaluation session, Ev2 presented the lowest symptoms and highest masticatory efficiency throughout therapy. Therefore, low intensity laser application is effective in reducing TMD symptoms, and has influence over masticatory efficiency [Ev2 (0.2423) and Ev3 (0.2043), observed in the interaction Evaluations x Probes for effective dosage].

Growth hormone therapy in Prader-Willi Syndrome

Prader-Willi syndrome (PWS) was originally described less than 50 y ago,1 although reference to children with characteristics of the syndrome are to be found in other literature previous to this.2 Until relatively recently the diagnosis was made upon the clinical features as outlined by Holm,3 which include severe muscular hypotonia in the neonatal period leading to feeding difficulties and undernutrition, hypogonadism and later hyperphagia and obesity. Latterly the syndrome has been identified as being associated with an interstitial deletion of the q11-13 region on chromosome 15.4 In the majority of cases the deletion is in the paternally derived chromosome. In the remainder of cases there seems to be a failure to inherit the entire paternal chromosome and as a consequence both the chromosomes inherited are maternal, thus leading to maternal disomy.

Specific manipulative therapy treatment for chronic lateral epicondylalgia produces uniquely characteristic hypoalgesia

The treatment of lateral epicondylalgia, a widely-used model of musculoskeletal pain in the evaluation of many physical therapy treatments, remains somewhat of an enigma. The protagonists of a new treatment technique for lateral epicondylalgia report that it produces substantial and rapid pain relief, despite a lack of experimental evidence. A randomized, double blind, placebo-controlled repeated-measures study evaluated the initial effect of this new treatment in 24 patients with unilateral, chronic lateral epicondylalgia. Pain-free grip strength was assessed as an outcome measure before, during and after the application of the treatment, placebo and control conditions. Pressure-pain thresholds were also measured before and after the application of treatment, placebo and control conditions. The results demonstrated a significant and substantial increase in pain-free grip strength of 58% (of the order of 60 N) during treatment but not during placebo and control. In contrast, the 10% change in pressure-pain threshold after treatment, although significantly greater than placebo and control, was substantially smaller than the change demonstrated for pain-free grip strength. This effect was only present in the affected limb. The selective and specific effect of this treatment technique provides a valuable insight into the physical modulation of musculoskeletal pain and requires further investigation. (C) 2001 Harcourt Publishers Ltd.

Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload

Background Icodextrin is a high molecular weight, starch-derived glucose polymer, which is capable of inducing sustained ultrafiltration over prolonged (12–16 hour) peritoneal dialysis (PD) dwells. The aim of this study was to evaluate the ability of icodextrin to alleviate refractory, symptomatic fluid overload and prolong technique survival in PD patients. Methods A prospective, open-label, pre-test/post-test study was conducted in 17 PD patients (8 females/9 males, mean age 56.8 ± 2.9 years) who were on the verge of being transferred to haemodialysis because of symptomatic fluid retention that was refractory to fluid restriction, loop diuretic therapy, hypertonic glucose exchanges and dwell time optimisation. One icodextrin exchange (2.5 L 7.5%, 12-hour dwell) was substituted for a long-dwell glucose exchange each day. Results Icodextrin significantly increased peritoneal ultrafiltration (885 ± 210 ml to 1454 ± 215 ml, p < 0.05) and reduced mean arterial pressure (106 ± 4 to 96 ± 4 mmHg, p < 0.05), but did not affect weight, plasma albumin concentration, haemoglobin levels or dialysate:plasma creatinine ratio. Diabetic patients (n = 12) also experienced improved glycaemic control (haemoglobin Alc decreased from 8.9 ± 0.7% to 7.9 ± 0.7%, p < 0.05). Overall PD technique survival was prolonged by a mean of 11.6 months (95% CI 6.0–17.3 months). On multivariate Cox proportional hazards analysis, extension of technique survival by icodextrin was only significantly predicted by baseline net daily peritoneal ultrafiltration (adjusted HR 2.52, 95% CI 1.13–5.62, p < 0.05). Conclusions Icodextrin significantly improved peritoneal ultrafiltration and extended technique survival in PD patients with symptomatic fluid overload, especially those who had substantially impaired peritoneal ultrafiltration.

Contrasting Epstein-Barr virus-specific cytotoxic T cell responses to HLA A2-restricted epitopes in humans and HLA transgenic mice: implications for vaccine design

This study investigates the hierarchy of cytotoxic T cell (CTL) responses to twelve HLA A2-restricted epitopes from the latent, lytic and structural proteins of Epstein–Barr virus (EBV) in acute infectious mononucleosis and in healthy seropositive donors and the relative immunogenecity of these epitopes in transgenic mice. Responses to the lytic epitope were uniformly strong in all healthy seropositive individuals and acute infectious mononucleosis donors while moderate or low responses were observed to the latent and structural epitopes, respectively in both groups studied. In contrast, when HLA A2/Kb transgenic mice were immunised with these peptide epitopes, CTL responses were observed to all epitopes with a maximal response to the epitopes within the structural proteins and low to moderate responses to the latent epitopes. This hierarchy of CTL responses in mice was also reflected in an MHC stabilisation analysis. These contrasting CTL responses in humans following natural infection compared to the immunogenicity of these epitopes and their ability to stabilise MHC may need to be considered when designing an EBV vaccine.

Adoptive transfer of autologous Epstein-Barr virus-specific cytotoxic T cells for nasopharyngeal carcinoma

Tumor cells from NPC patients are regularly and latently infected with EBV. To examine whether the virus serves as target for immune intervention of the cancer, we determined levels of EBV-specific CTLp in peripheral blood from NPC patients, long-term survivors of the cancer and healthy subjects. CTLp levels of test subjects varied between 3-3,000/10(6) PBMCs. The plasma EBV burden increased when the CTLp level fell below 150, whereas the EBV burden of PBMCs was not correlated with CTLp level. Compared with healthy carriers, CTLp levels of patients were lower and varied over a wider range, between 3-1,500/10(6) PBMCs. The quantitative immune deficit was probably attributed to the tumor because, first, CTLp in survivors was restored to levels similar to those in healthy carriers after the tumor had been successfully treated. Second, the CTLp level changed as disease progressed, being lower in local disease, increased in locoregional disease and decreased again when the tumor metastasized. Based on these findings, 4 patients with advanced disease were infused with 5 x 10(7)-3 x 10(8) autologous EBV CTLs. The treatment was safe and unaccompanied by inflammatory or other complications, but whether it improved tumor control could not be discerned from the large tumor bulk. Nevertheless, the treatment regularly increased CTLp levels of patients, maintained it at higher levels for protracted periods and, in 3 patients, restored host surveillance of EBV replication, reducing the plasma EBV burden. Taken together, these results provided a rationale to further explore EBV as a target of immune intervention of NPC. (C) 2001 Wiley-Liss, Inc.

Cognitive behaviour therapy for the management of obsessive-compulsive disorder

Current research reflects conflict regarding best practice in the treatment of obsessive-compulsive disorder (OCD). The. present study reports on the psychological treatment of a 54-year-old woman diagnosed with OCD, and follows the implementation of pharmacological treatment. The study utilises both exposure and response prevention (ERP) and cognitive therapy (CT), although there was no attempt to compare these approaches in an experimental design. Measures of avoiding and neutralising behaviours were taken on three occasions across treatment. Measures were also taken of intrusive thoughts, appraisal of responsibility, and effective challenging, both across treatment and at follow-up. The results indicate that gains were made in addition to those reported following the implementation of medication. The results also suggest that the addition of CT to exposure and response prevention facilitates the extinction of neutralising behaviours.