Promoter region polymorphisms in the transforming growth factor beta-1 (TGFß1) gene and serum TGFß1 concentration in preeclamptic and control Iranian women.

Preeclampsia (PE) is a pregnancy associated disorder characterized by hypertension and proteinuria, which causes neonatal and maternal morbidity and mortality. The Th1/Th2 cytokine paradigm of the immune adaptation in pregnancy is now expanded to include Th1/Th2/Th17 and regulatory T (Treg) cells. Among cytokines, TGFß1 has properties that justify evaluation of its role in PE etiopathology. In this investigation the polymorphisms of the TGFß1 gene at promoter region, positions -800G→A and -509C→T, were studied in 142 PE and 140 normal pregnant female subjects using PCR-RFLP. Additionally, serum TGFß1 was determined by ELISA. At position -800G→A genotypes and allele frequencies showed no significant differences between PE patients (GG 73.9%; GA 21.1%; AA 4.93%) and normal control (GG 70%; GA 28.6%; AA 1.4%) women. However the AA genotype at this position was more frequent in PE patients than in the control group. At -509C→T position, genotypes and allele frequencies showed no significant differences between PE patients and control individuals. The CC genotype at -509C→T position was more prevalent in PE patients than in the control group. The mean serum TGFß1 level was significantly higher (62.14 ng/ml) in PE patients compared with pregnant and non-pregnant control groups (and 47.01 and 40.68 ng/ml, respectively). In conclusion, the promoter region polymorphisms of TGFß1 may not be associated with PE, but serum levels of this cytokine may contribute to the etiopathology of PE.

The attenuation of pain behaviour and serum interleukin-6 concentration by nimesulide in a rat model of neuropathic pain.

Background Evidence for a role of immune system in hyperalgesic pain states is increasing. Recent work in neuroimmunology suggests that the immune system does more than simply perform its well known functions of recognizing and removing invading pathogens and tumors. Interest in neuroinflammation and neuroimmune activation has grown rapidly in recent years with the recognition of the role of central nervous system inflammatiom and immune responses in the aetiology of pain states. Among various theories, the role of inflammatory responses of the injured nerve has recently received attention. Cytokines are heterogenous group of polypeptides that activate the immune system and mediate inflammatory responses, acting on a variety of tissue, including the peripheral and central nervous system. Interleukin-6 (IL-6) a pro-inflammatory cytokine, is potentially important in pain aetiology, have pronociceptive actions. Neuropathic pain may be due to a primary insult to the peripheral or central nervous system. Substances released during inflammation from immune cells play an important role in the development and maintenance of chronic pain. Nimesulide, a highly selective cox-2 inhibitor, effectively reduces hyperalgesia due to peripherally administration of inflammatory agents like formalin. The safety of nimesulide was reported for some conditions in which other NSAIDs are contraindicated. Here we have determined the effect of nimesulide on pain behaviour and serum IL-6 level in chronic constriction injury (CCI) model of neuropathic pain. Methods Experiments were carried out on male Wistar rats, (weight 150-200 g, n = 8). Rats were divided into 3 different groups: 1-CCI + saline 0.9% 2Sham + saline 0.9% (control) 3CCI + drug. Nimesulide (1.25, 2.5, 5 mg/kg, i.p.) was injected 1h before surgery and continued daily to day 14 post-ligation. 42 °C water for thermal hyperalgesia, von Frey filaments for mechanical allodynia, acetone test for cool allodynia and 10 °C water for cold hyperalgesia were respectively used as pain behavioural tests. Behavioural tests were recorded before surgery and on postoperative days 1, 3, 5, 7, 10, 14 and the serum concentration of IL-6 was determined at the day 14. Results The results of this study showed a decrease in hyperalgesia and allodynia following nimesulide administration. Conclusions It appears that nimesulide was able to reduce pain behaviour due to nerve inflammation and a parallel decrease in the serum IL-6 concentration was observed. Implications The immune system is an important mediator in the cascade of events that ultimately results in hyperalgesia. Cytokines contribute to the patheogenesis of neuropathic pain, therefore drugs that inhibit cytokine release from immune cells may reduce inflammatory pain states.

Posttransplant soluble CD30 as a predictor of acute renal allograft rejection.

BACKGROUND: Recent results have indicated that high prerenal and postrenal transplant soluble CD30 levels may be associated with an increased acute rejection and graft loss. The aim of this study was to evaluate the feasibility of using serum sCD30 as a marker for predicting acute graft rejection. MATERIALS AND METHODS: In this prospective study,we analyzed clinical data of 80 patients, whose pretransplant and posttransplant serum levels of sCD30 were detected by enzyme-linked immunoassay. Eight patients developed acute rejection, 7 patients showed delayed graft function, and 65 recipients experienced an uncomplicated course group. The patients were followed for 12 months, and there were no deaths. RESULTS: Preoperative sCD30 levels of 3 groups were 96.2 -/+ 32.5, 80.2 -/+ 28.3, and 76.8 -/+ 29.8 U/mL (P = .28). After transplant, a significant decrease in the sCD30 level was detected in 3 groups on day 14 posttransplant (P < .001), while sCD30 levels of acute rejection group remained significantly higher than delayed graft function and nonrejecting patients (28.3 -/+ 5.2, 22.1 -/+ 3.2, and 19.8 -/+ 4.7 U/mL) (P = .02). Positive panel reactive antibody was not statistically different among groups (P = .05). Also, hemodialysis did not affect sCD30 levels (P = .05). Receiver operating characteristic curve demonstrated that the sCD30 level on day 14 posttransplant could discriminate patients who subsequently suffered acute allograft rejection (area under receiver operating characteristic curve, 0.95). According to receiver operating characteristic curve, 20 U/mL may be the optimal operational cutoff level to predict impending graft rejection (specificity 93.8%, sensitivity 83.3%). CONCLUSIONS: Measurement of the soluble CD30 level on day 14 after transplant might offer a noninvasive means for recognizing patients at risk of acute graft rejection during the early posttransplant period.

Spinal mu-opioid receptor expression and hyperalgesia with dexamethasone in chronic adjuvant-induced arthritis in rats.

1. It is known that inflammation influences peripheral and central mu-opioid receptor expression. Previous studies have indicated that glucocorticoids may influence the density of mu-opioid receptors. In the present study, we investigated the fluctuations of spinal mu-opioid receptor expression and hyperalgesia induced by complete Freund's adjuvant (CFA) under long-term administration of dexamethasone. 2. Adjuvant arthritis (AA) was induced by subcutaneous injection of CFA in the right hindpaw of male Wistar rats. Spinal mu-opioid receptor expression was detected by semiquantitative reverse transcription-polymerase chain reaction on Days 6 and 21 following AA induction. Dexamethasone (0.1 mg/kg) was administered intraperitoneally for 21 days. Variations in thermal hyperalgesia were checked by radiant heat on the same days as mu-opioid receptor expression was determined. 3. The results indicated a significant increase in spinal mu-opioid receptor expression on Days 6 and 21 after AA induction compared with the control group. Spinal mu-opioid receptor expression decreased significantly only on Day 21 in the AA + dexamethasone group compared with the AA alone group. Thermal hyperalgesia on Day 6 after AA induction showed a significant increase compared with the control group. Hyperalgesia decreased significantly on Day 21 after AA compared with Day 6. The AA + dexamethasone group showed a significant decrease in hyperalgesia on Day 6 compared with the AA group, but hyperalgesia increased significantly on Day 21 in the AA + dexamethasone group compared with the AA group. 4. The effects of long-term dexamethasone on both spinal mu-opioid receptor expression and hyperalgesia during persistent AA inflammation are time dependent. In addition, the effect of long-term dexamethasone administration on hyperalgesia during persistent arthritis inflammation needs to be investigated further.

Effect of low-level laser therapy on skin fibroblasts of streptozotocin-diabetic rats.

OBJECTIVE: This study explored the effects of low-level laser therapy (LLLT) on cellular changes in cell culture and organ culture of skin from streptozotocin-diabetic (STZ-D) rats. BACKGROUND DATA: Growth of skin and its fibroblasts are impaired in diabetes. Therefore the healing of skin wounds is impaired in diabetic patients. The positive effects of LLLT on complications of diabetes in patients and animal models have been shown. METHODS: Diabetes was induced in rats by streptozotocin 30 days after its injection. Two sets of skin samples were extracted from skin under sterile conditions. Fibroblasts that were extruded from the samples were proliferated in vitro, and another set of samples were cultured as organ culture. A 24-well culture medium containing Dulbecco's modified minimum essential medium was supplemented by 12% fetal bovine serum. There were five laser-treated and five sham-exposed groups. A helium-neon laser was used, and 0.9-4 J/cm(2) energy densities were applied four times to each organ culture and cell culture. The organ cultures were analyzed by light microscopy and transmission electron microscopy examinations. Cell proliferation was evaluated by dimethylthiazol-diphenyltetrazolium bromide (MTT) assay. RESULTS: Statistical analysis revealed that 4-J/cm(2) irradiation significantly increases the fibroblast numbers compared to the sham-exposed cultures (p = 0.046). CONCLUSION: It is concluded that LLLT resulted in a significant increase of fibroblast proliferation of STZ-D rats in vitro.

Suppression of interleukin-6 by minocycline in a rat model of neuropathic pain.

Inflammatory mediators produced in the injured nerve have been proposed as contributing factors in the development of neuropathic pain. In this regard an important role is assigned to interleukin-6. The present study, evaluated the effect of pretreatment with minocycline, on pain behavior (hyperalgesia and allodynia) and serum level of interleukin-6 in chronic constriction injury (CCI) model of neuropathic pain in rat. Minocycline (5, 10, 20 and 40 mg/kg, i.p.) was injected 1 h before surgery and continued daily to day 14 post-ligation. Behavioral tests were recorded before surgery and on postoperative days 1, 3, 5, 7, 9, 10, 14, and the serum concentration of interleukin-6 was determined at day 14. We observed that minocycline which was reported to have a neuroprotective effect in some neurodegenerative diseases, reversed hyperalgesia and allodynia due to sciatic nerve ligation and inhibited the interleukin-6 production. It seems that minocycline could have an anti-inflammatory and analgesic effect in some chronic pain states.