Evaluation of Arthrocentesis with hyaluronic acid injections for management of temporomandibular disorders: a systematic review and case series.

Although arthrocentesis is an accepted safe treatment modality for the management of temporomandibular disorders (TMD) in symptomatic patients, the benefit of hyaluronic acid (HA) injections remains uncertain. The aim of this study was to evaluate whether intra-articular HA injections adjunctive to arthrocentesis can be more effective than other medications for the improvement of TMD associated symptoms. Additionally, the impact of HA injections on quality of life of TMD patients was assessed with SF-36® questionnaire in a cohort of patients. An electronic search of Medline, Scopus and Cochrane databases was performed up to March 2020. The following search terms were used: "arthrocentesis", "hyaluronic acid", "intra-articular injections", "visco-supplementation", "temporomandibular disorders". Prospective and retrospective studies that reported the application of HA injections compared to other intra-articular drugs for the treatment of temporomandibular disorders were included. Systematic or narrative reviews and pre-clinical studies were excluded. Additionally, a retrospective clinical study was performed for evaluation of changes in quality of life before and after arthrocentesis with HA injections. In the systematic review, the initial search yielded 1327 articles. After screening of the titles, abstracts, and full texts, 29 studies were selected (26 randomized studies, 2 controlled clinical trials, 1 retrospective report). In the clinical study, 12 patients were included. Intra-articular injections of HA and other medications together with arthrocentesis seemed to be beneficial for improvement of functional symptoms of TMD and pain. The case series also supported the efficacy of HA injections showing an improvement of quality of life of these patients. However, from literature review, it was impossible to identify an optimum drug or a protocol for predictably improving the pain and/or functional symptoms of temporomandibular problems, due to different etiologies, diversity of treatment modalities and conflicting results. In conclusion, there is no consensus in the literature that HA injections shows better results in comparison with other treatment modalities. According to the results of the present clinical study, HA injections with/without arthrocentesis seems to be beneficial in terms of clinical symptoms and quality of life of the TMD patients.

Role of probiotics in adjunct to non-surgical periodontal therapy in patients with chronic periodontitis: a systematic review and meta-analysis.

The objective of this study was to establish the significance of probiotic usage, both as a preventive as well as a therapeutic strategy for the management of periodontal disease. It also substantiates the existing studies of single/combined bacterial strain for exhibiting variable ecological impact on oral bacteria. Data sources included literature searches of PubMed (MEDLINE), Scopus, Embase, CENTRAL and Web of science databases for placebo controlled randomized clinical trials of SRP with orally administered probiotics in any form as an adjunct. Data extraction was conducted and information from the included studies was tabulated according to the study designs, form of drug delivery, main outcomes, and clinical parameters. Data collected were based on the focused question outlined for the present systematic review. The reviewers cross-checked all extracted data. CAL and PD were assessed as the primary outcome to compare the effectiveness of adjunctive probiotic therapy in addition to SRP. Fourteen clinical studies were included and demonstrated efficacy in reducing periodontal probing depth (PPD) and gaining clinical attachment level (CAL), between probiotics and SRP/placebo. Adjunctive probiotic therapy in addition to SRP leads to decrease in probing depth and clinical attachment gain in chronic periodontitis patients. However, further high-quality randomized clinical trials with microbiological outcomes are required to fortify the conclusion.

Clinical efficacy of grape seed extract as an adjuvant to scaling and root planing in treatment of periodontal pockets.

Grape seed extract (GSE), a naturally producing polyphenolic compound, is found to be a potent hostmodulatory agent and considered for management of periodontal disease. Its anti-bacterial, antioxidant, and anti-inflammatory property may aid in achieving periodontal health. To assess the clinical efficacy of GSE in adjunct to scaling and root planing (SRP) in healing of periodontal pockets. The present study was a longitudinal, parallel design, randomized clinical trial. Seventy-two patients (mean age 39.2±8.6 years) with periodontal pockets were randomly divided into two groups; Test group received intra-pocket delivery of GSE with SRP and Control group received SRP alone. The clinical parameters like Plaque Index (PI), Gingival Index (GI), Probing Depth (PD) and Relative Attachment Level (RAL) were recorded at baseline and 3 months. 64 patients completed the study. Test group at the end of 3 months had statistically significant reduced PD (p=0.002) and RAL (p=0.01). No significant difference was observed for PI and GI at the end of 3 months. Intra-pocket application of GSE with SRP could be beneficial in management of periodontal pockets.

Knowledge, practices and perceptions regarding oral health preventive measures among Mexican dental students: a cross-sectional survey study.

Although oral diseases are mostly preventable, they remain a global public health problem. Thus, there is a need for trained personnel to actively intervene in promoting oral health, to prevent and timeously detect oral diseases, and, in turn, to provide comprehensive quality healthcare. The main objective of the study was to evaluate the knowledge, practices and perceptions regarding oral health preventive measures amongst undergraduate dental students. This cross-sectional study was conducted between the period October 2017 and January 2018. The subjects included were undergraduate students of the dental science program at the School of Dentistry, in Leon Guanajuato, Mexico. A validated questionnaire was used to identify knowledge of preventive dentistry and the frequency of oral health preventive actions in the dental school clinics. Besides, perception towards prevention in dentistry was assessed. A total of N=232 undergraduate students participated of whom 65.9% (N=153) were women. More than half of the students 59.5%, (N=138) rated their knowledge on the prevention of oral diseases as good, followed by 32.8% (N=75) of students who rated it as regular. 49% (N=97) of the students performed frequently preventive treatments in their daily clinical practice. 90% (N=217) think that the main reason of low practice of prevention in dentistry is the lack of commitment of the dentist. 72.8% (N=169) mention that there should be professionals dedicated exclusively to preventive dentistry. Students of second grade demonstrated better prevention knowledge and tended to engage more frequently in preventive activities (p<0.05). In conclusion, our study found that, second-year students perform preventive practices more frequently and these practices decrease as their studies progress. It should be sought to create positive attitudes towards prevention not only in the year in preventive dentistry, but also throughout the entire career. This enables students to become trained professionals that can deliver preventive services to their patients.

Clinical effectiveness of Lactobacillus reuteri in the treatment of peri-implant diseases: a systematic review and meta-analysis.

In the last decades, the presence of peri-implant diseases (PD) has increased. One of the therapies currently used is probiotics with Lactobacillus reuteri (LR). The aim of this article is to determinate, through a systematic review and meta-analysis, the clinical effectiveness of LR in the treatment of PD. We searched the literature until January 2021, in the biomedical databases: Pubmed, Embase, Scielo, Science Direct, Scopus, SIGLE, LILACS, Google Scholar and Cochrane Central Registry of Clinical Trials. The selection criteria of the studies were: randomized controlled clinical trials, without language and time restriction, reporting the clinical effects (depth to probing, plaque index and bleeding index) of the LR in the PD treatment. The risk of study bias was analyzed through the Cochrane tool for randomized studies using Review Manager software. The search strategy resulted in 6 articles of which four investigated peri-implantitis and three peri-implant mucositis. All studies reported that there was a difference in the depth of the probing in the treatment of PD, in favor of the group using LR, though not always achieving significance. The use of LR can be clinically effective in terms of pocket depth reduction in the treatment of PD.

The hydrogen sulphide-releasing derivative of diclofenac protects against ischaemia-reperfusion injury in the isolated rabbit heart.

BACKGROUND AND PURPOSE: Hydrogen sulphide (H(2)S) is an endogenous gaseous mediator active in the multilevel regulation of pathophysiological functions in mammalian cardiovascular tissues. EXPERIMENTAL APPROACH: This study investigated the pharmacological activity of a new H(2)S-releasing derivative of diclofenac, S-diclofenac (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid 4-(3H-1,2-dithiole-3-thione-5-yl)-phenyl ester) in the isolated rabbit heart submitted to low-flow ischaemia-reperfusion damage. KEY RESULTS: S-diclofenac (3, 10 and 30 microM), despite inhibiting prostacyclin generation by cardiac tissues, achieved dose-dependent normalization of coronary perfusion pressure, reducing left ventricular contracture during ischaemia and improving left ventricular developed pressure and +/-dP/dt(max) at reperfusion. Creatine kinase and lactate dehydrogenase activities in heart perfusates were significantly reduced during reperfusion. These effects were accompanied by substantial release of reduced glutathione (GSH), indicating that the H(2)S moiety may have up-regulated cysteine transport. The anti-ischaemic activities of S-diclofenac and the H(2)S-donor sodium hydro sulphide (NaHS) were partially prevented by the K(ATP) channel antagonist glibenclamide, suggesting a mechanism similar to H(2)S-induced cardioprotection in metabolic ischaemic preconditioning. Perfusion with the nitric oxide (NO) synthase inhibitor N(G)-monomethyl-L-arginine worsened the myocardial ischaemia-reperfusion damage, but this was dose-dependently prevented by S-diclofenac and NaHS, suggesting that the released H(2)S may have overcome NO deficiency. CONCLUSION AND IMPLICATIONS: These data show that S-diclofenac had marked anti-ischaemic activity in ischaemic-reperfused rabbit hearts despite inhibition of prostaglandin generation. Increased GSH formation leading to activation of K(ATP) channels may have contributed to this beneficial effect. The pharmacological profile of S-diclofenac and its anti-inflammatory activity, with diminished gastrointestinal side effects, offer therapeutic applications in cardiovascular disease.

Sildenafil reduces L-NAME-induced severe hypertension and worsening of myocardial ischaemia-reperfusion damage in the rat.

BACKGROUND AND PURPOSE: Phosphodiesterase-5 inhibitors are beneficial in pulmonary hypertension and congestive heart failure, the two conditions associated with coronary heart disease and ischaemia. We investigated whether sildenafil counteracts the cardiovascular alterations induced by N -nitro-L-arginine methyl ester (L-NAME) in the rat. EXPERIMENTAL APPROACH: Sildenafil was given orally to rats at doses of 0.37, 0.75 or 1.5 mg kg-1day-1 for four weeks, either alone or with L-NAME (35-40 mg kg-1 day-1 in the drinking water). Systolic blood pressure and urinary parameters (6-keto-prostaglandin F1alpha, thromboxane B2, 8-isoprostane-prostaglandin F2 and nitrite/nitrate) were measured in conscious rats. Isolated hearts were subjected to low flow ischaemia-reperfusion, and myocardial levels of guanosine 3', 5'cyclic monophosphate (cGMP) were determined. Endothelial vascular dysfunction was examined in aortic rings. KEY RESULTS: Sildenafil dose-dependently prevented the rise in systolic blood pressure in L-NAME-treated rats. This activity was associated with a normalization of urinary 8-isoprostane-prostaglandin F2alpha and other biochemical parameters. In perfused hearts, the post-ischaemic ventricular dysfunction was worse in preparations from L-NAME-treated rats than in controls. Sildenafil dose-dependently reduced this effect, and creatine kinase and lactate dehydrogenase release were lower too. cGMP levels, which were low in myocardial tissue from L-NAME-treated rats, were restored by sildenafil. In noradrenaline-precontracted aortic rings from L-NAME-treated rats acetylcholine lost its vasorelaxant effect, and sildenafil restored it. CONCLUSION AND IMPLICATIONS: In a rat model of chronic nitric oxide deprivation, where hypertension and aggravation of post-ischaemic ventricular dysfunction are associated with loss of vascular endothelium-relaxant function, sildenafil provided significant cardiovascular protection, primarily by maintaining tissue cGMP levels.

Intracerebroventricular interleukin-1 alpha increases immunocyte beta-endorphin concentrations in the rat: involvement of corticotropin-releasing hormone, catecholamines, and serotonin.

The opioid peptide beta-endorphin (BE) is synthesized and secreted by the cells of the immune system and has been shown to participate in the modulation of immune responses, e.g. during stress. Interleukin-1 (IL-1) is a potent activator of the corticotropin-releasing hormone (CRH) system in the hypothalamus, and it has been shown to be involved in many stress responses, including immunosuppression. We studied the effect of centrally injected IL-1 alpha on immunocyte BE concentrations in the rat. IL-1 alpha (1 ng/rat, intracerebroventricularly) significantly (P < 0.01) increased the concentrations of the peptide in splenocytes, lymph node cells, and peripheral blood mononuclear cells 2 and 24 h after treatment. Intracerebroventricular, but not iv, administration of 2 micrograms IL-1 receptor antagonist blocked the IL-1 alpha-induced increase. These effects were also prevented by the intracerebroventricular administration of the CRH receptor antagonist alpha-helical CRH-(9-41). Treatment with 6-hydroxydopamine and 5,7-dihydroxytryptamine, which deplete the catecholaminergic or the serotoninergic systems, respectively, blocked the increase in BE induced by the cytokine. In contrast, hypophysectomy and treatment with indomethacin did not modify the effect of IL. The increase in immunocyte BE, therefore, seems to depend on the activation of CRH, catecholamines, and serotonin, but to be independent of activation of the hypothalamus-pituitary-adrenal-axis and prostaglandins. The immunocyte BE increase could be involved in the immunosuppression induced by central IL-1 alpha.

Effects of tramadol on immune responses and nociceptive thresholds in mice.

Tramadol is a centrally acting analgesic drug with a dual mechanism of action: binding to mu-opioid receptors and potentiation of the monoaminergic systems. In this study, we evaluated the effects of the acute and chronic administration of tramadol on nociceptive thresholds (by the hot-plate test) and on immune responses (by measuring Concanavalin A-induced splenocyte proliferation, IL-2 production and natural killer activity) in the mouse. After acute subcutaneous administration, tramadol induced antinociception starting from a dose of 20 mg/kg, whereas it significantly enhanced natural killer activity and IL-2 production at doses as low as 1 mg/kg and splenocyte proliferation starting from a dose of 10 mg/kg. After the chronic administration, the antinociceptive effect of the drug was still present, whereas the immune modifications disappeared. Thus, the pharmacological profile of tramadol is totally different from that of other drugs which bind mu-opioid receptors. Our results suggest that tramadol could be a good choice for the treatment of pain in patients where immunosuppression may be particularly contraindicated.

Novel effect of nefopam preventing cGMP increase, oxygen radical formation and neuronal death induced by veratridine.

Nefopam hydrochloride is a potent analgesic compound that possesses a profile distinct from that of opiods or anti-inflammatory drugs. Previous evidence suggested a central action of nefopam but the detailed mechanisms remain unclear. Here we have used cultured cerebellar neurons to test the hypothesis that nefopam may modulate voltage sensitive sodium channel (VSSC) activity. Nefopam (100 microM) effectively prevented NMDA receptor-mediated early appearance (30 min) of toxicity signs induced by the VSSC activator veratridine. Delayed neurotoxicity by veratridine occurring independently from NMDA receptor activation, was also prevented by nefopam. In contrast, excitotoxicity following direct exposure of neurons to glutamate was not affected. Neuroprotection by nefopam was dose-dependent. 50% protection was obtained at 57 microM while full neuroprotection was achieved at 75 microM nefopam. Veratridine-induced sodium influx was completely abolished in nefopam-treated neurons. Intracellular cGMP and oxygen radical formation following VSSC stimulation by veratridine were also effectively prevented by nefopam. Our data are consistent with an inhibitory action of nefopam on VSSC and suggest that nefopam may modulate the release of endogenous glutamate following activation of these channels. This novel action of nefopam may be of great interest for the treatment of neurodegenerative disorders involving excessive glutamate release and neurotransmission.

The beta-endorphin inhibition of mitogen-induced splenocytes proliferation is mediated by central and peripheral paracrine/autocrine effects of the opioid.

In this study we show that the opioid peptide beta-endorphin exerts a tonic inhibitory effect on the proliferative response of splenocytes to the polyclonal mitogen phytohemoagglutinin throughout two separate sites of action: one central and one peripheral. The intracerebroventricular administration of beta-endorphin, in fact, induces a significant inhibition of splenocyte proliferation. In contrast, both the intracerebroventricular and the peripheral administration of anti-beta-endorphin gamma globulins induce a significant increase in proliferation. Moreover, an increase of splenocyte proliferation was observed also after the intravenous administration of gamma globulins and intraperitoneal naloxone, and this effect was still present in hypophysectomized rats. The data reported suggest that beta-endorphin exerts a tonic inhibitory effect on proliferation, acting centrally, and peripherally throughout a paracrine/autocrine mechanism. FACS experiments show that the effect observed is not the consequence of an alteration of lymphocyte trafficking induced by the opioid.

Regulation of immune functions in rat splenocytes after acute and chronic in vivo treatment with CP-55,940, a synthetic cannabinoid compound.

Changes in mitogen-induced splenocyte proliferation and NK activity were evaluated after acute (1 h) and chronic (6 d) in vivo treatment of rats with the synthetic cannabinoid compound CP-55,940. At a dose of 0.4 mg/kg i.p. it significantly inhibited the splenocyte proliferative response to PHA and NK activity but half this dose (0.2 mg/kg) had no effect on immune responses. Pretreatment of rats with the cannabinoid receptor CB1 antagonist SR141716A did not antagonize the CP-55,940-induced immunosuppression, excluding the activation of this receptor subtype in the mediation of this effect. When immune function studies were done on rats tolerant to CP-55,940-induced analgesia, full tolerance also developed for the inhibition of splenocyte proliferation and NK activity. The data provided indicate that CB1 cannabinoid receptors are not involved in mediating the acute and chronic effects of cannabinoids on the immune system and suggest a possible implication of CB2 receptor although other modalities of CP-55,940 action can not be ruled out.

Evidence for an opioid inhibitory effect on T cell proliferation.

The proliferative response of human or rat T lymphocytes to phytohemagglutinin (PHA) or concanavalin A (ConA) was measured after acute (30 min) or chronic (8 days) treatment with the opiate receptor antagonists naloxone or naltrexone. Both in the rat and in the human, proliferation was significantly enhanced by acute treatment with the opiate receptor antagonists. In contrast, after chronic treatment proliferation always decreased. The sudden removal of an opioid inhibitory tone might be the basis for the increased proliferative responses observed after acute treatment. The decrease after chronic treatment could be ascribed to the amplification of the inhibitory effect of endogenous opioids due to the up-regulation of opiate receptors that follows chronic antagonist administration. Receptor binding studies of beta-endorphin receptors on splenocytes of chronically naloxone treated rats confirmed this hypothesis: a higher number of beta-endorphin receptors were expressed on splenocytes of naloxone-treated rats compared to controls (Bmax = 9.8 x 10(-12) vs. 1.16 x 10(-12), respectively).

Beta-endorphin concentrations in brain areas and peritoneal macrophages in rats susceptible and resistant to experimental allergic encephalomyelitis: a possible relationship between tumor necrosis factor alpha and opioids in the disease.

Since the central nervous system and neuropeptides modulate immune functions, we investigated whether the different susceptibility of Lewis and Brown Norway rats to experimental allergic encephalomyelitis could also reflect differences in beta-endorphin and substance P concentrations in brain areas and macrophages during the development of the disease. We show that beta-endorphin concentrations increase much more in the hypothalamus and macrophages of Lewis rats during the development of the disease, while the increase is much lower or absent in Brown Norway rats. Tumor necrosis factor-alpha seems to play an important role in this difference. The administration of the opiate receptor antagonist naltrexone worsens the development of the disease, suggesting that the increase of the opioid beta-endorphin might represent a mechanism to downregulate the immune response. In both strains, the concentrations of substance P do not change.

Immune function alterations in mice tolerant to delta9-tetrahydrocannabinol: functional and biochemical parameters.

We studied the effect of acute (1 h) or chronic exposure (7 and 14 days) to delta9-tetrahydrocannabinol (delta9-THC) on immune parameters in male Swiss mice. One hour after a dose of 10 mg/kg s.c., the splenocyte proliferative response to ConA and NK activity were not inhibited, but there was a significant decrease in the production of IL-2. After 7 days of treatment, when mice were tolerant to delta9-THC-induced analgesia, these functional parameters were strongly inhibited and there was a persistent reduction in IL-2 and IFNgamma. With 14 days exposure to the drug, splenocyte proliferation was significantly reduced only with 5 microg/ml ConA, and NK activity was still significantly depressed (about 37%). IL-2 had returned to the control value, whereas IFNgamma was still 40% down. Flow cytometry analysis of spleen cell composition indicated no changes after the acute and 7 day treatments, but at 14 days there was a 20% decrease in the number of T lymphocytes, mirrored by a 26% increase of B lymphocytes. In conclusion, in vivo exposure to psychoactive doses of delta9-THC has profound effects on immune function. This implies some important questions in relation to the liberalization of marijuana and its therapeutic uses.

Antinociceptive and immunosuppressive effects of opiate drugs: a structure-related activity study.

1. Although it is well known that morphine induces significant immunosuppression, the potential immunosuppressive activity of morphine derived drugs commonly used in the treatment of pain (codeine, hydromorphone, oxycodone) has never been evaluated. 2. We evaluated in the mouse the effect of the natural opiates (morphine and codeine) and synthetic derivatives (hydromorphone, oxycodone, nalorphine, naloxone and naltrexone) on antinociceptive thresholds and immune parameters (splenocyte proliferation, Natural Killer (NK) cell activity and interleukin-2 (IL-2) production). 3. Morphine displayed a potent immunosuppressive effect that was not dose-related to the antinociceptive effect, codeine possessed a weak antinociceptive effect and limited immunosuppressive activity; nalorphine, a mu-antagonist and kappa-agonist, exerted a potent immunosuppressive effect, but had very weak antinociceptive activity. The pure kappa-antagonist nor-BNI antagonized the antinociceptive, but not the immunosuppressive effect of nalorphine. 4. Hydromorphone and oxycodone, potent antinociceptive drugs, were devoid of immunosuppressive effects. 5. The pure antagonists naloxone and naltrexone potentiated immune responses. 6. Our data indicate that the C6 carbonyl substitution, together with the presence of a C7-8 single bond potentiates the antinociceptive effect, but abolishes immunosuppression (hydromorphone and oxycodone). 7. The single substitution of an allyl on the piperidinic ring resulted in a molecule that antagonized the antinociceptive effect but maintained the immunosuppressive effect. 8. Molecules that carry modifications of C6, the C7-8 bond and C14, together with an allyl or caboxymethyl group on the piperidinic ring antagonized both the antinociceptive and the immunosuppressive effect of opiates and were themselves immunostimulants.

Beta-endorphin concentrations in resting peripheral mononuclear cells and after treatment with PHA or serotoninergic drugs in human aging, Alzheimer's disease, and Down's syndrome.

We measured the concentrations of beta-endorphin in resting peripheral blood mononuclear cells obtained from normal subjects of different ages and from age-matched patients with Down's syndrome or Alzheimer's disease. We also measured beta-endorphin concentrations in peripheral blood mononuclear cells obtained from subjects of different ages after treatment with PHA or serotoninergic drugs. The results show that in normal subjects the concentrations of the peptide increase after 30 years of age and remain constant up to 99 years. After stimulation with PHA, the release of beta-endorphin in cells from subjects older than 30 years increases, leading to a decrease in contents, whereas it is unchanged in younger subjects. In patients with Down's syndrome or Alzheimer's disease, beta-endorphin concentrations in peripheral blood mononuclear cells behave similarly to those in age-matched normal subjects. Treatment in vivo with the serotoninergic agonist chlorimipramine induces an increase in beta-endorphin concentrations in peripheral blood mononuclear cells that is significantly greater in subjects over 30 years old than in younger subjects.

Chronic administration of UK-114, a multifunctional emerging protein, modulates the Th1/Th2 cytokine pattern and experimental autoimmune diseases.

UK-114 is a 14-kDa ubiquitous protein recently sequenced by several groups throughout the world. Its activity ranges from being a tumor antigen, a protein synthesis inhibitor or a specific mu-calpain activator. UK-114 shows structural homologies also with proteins of the MHC-1 binding proteins, and heat shock proteins (HSPs). We investigated the possible effects of UK-114 on T helper cells cytokine profile and the development and progression of experimental autoimmune diseases. Homogeneous recombinant UK-114 was used in all experiments. Treatment of Balb/c male mice for two weeks resulted in the increase of IL-4, and the decrease of TNF-alpha, IFN-gamma, and IL-2 release from stimulated splenocytes, suggesting that UK-114 modulates the Th1/Th2 cytokine profile toward Th2. Similar to that observed with HSP60/65, a single pretreatment of Lewis rats with UK-114 significantly blunted the development of adjuvant-induced arthritis, whereas chronic treatment of 4-week-old female NOD mice dose dependently inhibited the development of diabetes.

Mononuclear cell beta-endorphin concentration in women with and without endometriosis.

Seventy-five consecutive patients undergoing laparoscopy for chronic pelvic pain and/or infertility were studied to test whether beta-endorphin concentrations in peripheral mononuclear cells differed according to the presence or absence of endometriosis. Endometriosis was diagnosed in 45 subjects (minimal in 24, mild in 11, moderate in four, and severe in six). Twenty-eight women (62%) with endometriosis and ten (33%) without the disease reported moderate or severe pelvic pain. beta-Endorphin levels were lower in the endometriosis group than in the controls (16.6 +/- 11.2 versus 21.9 +/- 10.5 pg/10(6) cells; P less than .01). This decrease was attributable to reduced beta-endorphin concentrations in the endometriosis patients with moderate or severe pain compared with symptomatic controls (15.5 +/- 10.0 versus 26.3 +/- 7.0 pg/10(6) cells; P less than .01). A significant difference was also found in relation to the cycle phase: The opioid concentration was reduced in the luteal phase in the endometriosis group compared with controls (14.4 +/- 8.4 versus 23.8 +/- 7.5 pg/10(6) cells; P less than .01), but no differences were demonstrated in the follicular and periovulatory phases. beta-Endorphin is capable of modulating the immune response and can be considered as a classical cytokine. Low beta-endorphin production during the luteal phase may have implications in the development and/or maintenance of endometriosis.

Age-related changes in mitogen-induced beta-endorphin release from human peripheral blood mononuclear cells.

beta-Endorphin is an opioid peptide synthesized in the pituitary, hypothalamus, and immunocytes, known to affect immune responses both when added in vitro and when its synthesis is increased in vivo (e.g., during stress). We show here that, similar to its concentrations in peripheral blood mononuclear cells, the release of the opioid peptide from these cells after stimulation with polyclonal mitogens such as PHA or Con-A is also age dependent. Moreover, the effect of both mitogens on Ca2+ homeostasis changes with age. Finally, the ionophore ionomycin and the Ca2+ ATPase blocker thapsigargin induce the same age related effect on beta-endorphin release. For these reasons, we suggest that calcium homeostasis might be important for the differences observed in the release of the opioid from cells obtained from younger (< or = 30 years) or older (> or = 45 years) volunteers.