Impact of chronic lithium treatment on brain oxidative stress and anxiety-like behaviors in rats: Dose-dependent effects.

Lithium (Li) is a mood-stabilizing drug. Although one of the potential mechanisms underlying the neuroprotective effects of lithium is related to its antioxidative effect, its mechanisms of action are not fully understood. Herein we aimed to investigate the impact of varied dosages of long-term lithium therapy on oxidative stress parameters in the brains of healthy rats, and on anxiety-like behaviors, and whether any changes in behavior can be attributed to modifications in oxidative stress levels within the brain. Thirty-two adult Wistar albino male rats were randomly assigned to four treatment groups. While the control (C) group was fed with a standard diet, low Li (1.4 g/kg/diet), moderate Li (1.8 g/kg/diet), and high Li (2.2 g/kg/diet) groups were fed with lithium bicarbonate (Li2CO3) for 30 days. Malondialdehyde increased, while superoxide dismutase and catalase levels decreased in the brains of the high Li group animals. In addition, anxiety-like behaviors of animals increased in the high Li group considering fewer entries to and less time spent in the open arms of the elevated plus maze test. Our findings underscore the potential adverse effects of prolonged lithium treatment, especially at doses approaching the upper therapeutic range. The induction of toxicity, manifested through heightened oxidative stress, appears to be a key mechanism contributing to the observed increase in anxiety-like behaviors. Consequently, caution is warranted when considering extended lithium therapy at higher doses, emphasizing the need for further research to delineate the precise mechanisms underlying these effects and to inform safer therapeutic practices.

Impact of Lithium on the Immune System: An Investigation of T-Cell Subpopulations and Cytokine Responses in Rats.

The aim of this study was to investigate the dose-dependent adverse effects of long-term dietary lithium administration on specific aspects of the defense system in rats. Additionally, the study aimed to explore the inflammatory activities of lithium beyond its recognized anti-inflammatory properties. Forty Wistar Albino rats were involved, which were randomly allocated into the control and four treatment groups. The control group received standard rat feed, and the experimental groups' diet was added 1 g/kg, 1.4 g/kg, 1.8 g/kg, and 2.2 g/kg lithium bicarbonate, respectively. CD4+, CD8+, and CD161 + cells were assessed by flow cytometry. TNF-α, IFN-γ, IL-1ß, and IL-2 and IL-4, IL-6, and IL-10 levels were measured. The proportion of CD4 + cells and the CD4+/CD8 + ratio (P = 0.005 and P = 0.038, respectively) were reduced with the highest dose of lithium compared to the control group. The data regarding pro-inflammatory cytokines showed a dose-dependent increase in serum TNF-α and IFN-γ levels (P = 0.023 and P = 0.001, respectively). On the other hand, serum IL-1ß and IL-2 levels were decreased in a dose-dependent manner (P = 0. 001 and P = 0. 001, respectively). As for anti-inflammatory cytokines, a dose-dependent decrease was determined in serum IL-4 level (P = 0.002), while no significant changes were noted in IL-6 and IL-10 levels (P = 0.507 and P = 0.732, respectively). In conclusion, lithium adversely impacted the cellular defense system. Furthermore, apart from its anti-inflammatory properties, lithium exhibited cytokine-mediated inflammatory activities. Therefore, lithium's potential adverse effects on the immune system should be considered in immunodeficient patients and those with an inflammatory status treated with high doses of lithium.

The Relationship Between Inflammatory Processes and Apoptosis in Lumbar Disc Degeneration.

OBJECTIVE: Degenerative Disc Disease (DDD) is a common health problem in the population. There are recent studies focusing on relationship between DDD and immunological factors. However, there is still a lack of data on the role of apoptosis in DDD pathophysiology. Therefore, we aimed to investigate the relationship between Modic-type changes and the apoptosis in DDD. MATERIALS AND METHODS: Ninety adult male patients who presented with low back and/or radicular pain and were operated on due to lumbar disc herniation were included. Three groups were formed based on Modic type degeneration observed on magnetic resonance imaging. Specific parameters involved in the intrinsic and extrinsic pathways of apoptosis were assessed in excised disc materials using the enzyme-linked immunosorbent assay method. RESULTS: All three groups formed according to Modic degeneration types were homogenous in all variances. Cytochrome-C was significantly decreased only in the Modic type-3 group, whereas Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor-1, B-Cell Lymphoma-2 (Bcl-2) Homologous Antagonist Killer-1, Direct Inhibitor of Apoptosis-Binding Protein with Low Pi, and Bcl-2 Associated X Apoptosis Regulator levels were significantly different in both Modic type-2 and -3 groups. However, BH3 interacting domain death agonist and Bcl-2 levels were similar across all groups. CONCLUSIONS: In conclusion, this study suggests that Direct Inhibitor of Apoptosis-Binding Protein with Low Pi, cytochrome - c, Bcl-2 Associated X Apoptosis Regulator, Bcl-2 Homologous Antagonist Killer-1, and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor-1proteins play important roles in the development and progression of DDD and are correlated with Modic types. Further studies are needed to explore the potential therapeutic role of inhibiting these apoptotic proteins in DDD.

Imaging of the lower punctum with anterior segment OCT in patients with dacryocystorhinostomy who underwent bicanalicular silicone tube implantation.

Spectral domain OCT imaging of the lower punctum in cases with silicone tube implantation OBJECTIVE: To record the structural changes in the lower punctum by performing spectral domain anterior segment OCT imaging of dacryocystorhinostomy cases who underwent bicanalicular silicone tube implantation. METHODS: Thirty eyes of 30 patients who underwent bicanalicular Crawford silicone tube implantation with dacryocystorhinostomy were included in the study. The mean age of the cases was 53 ± 13.96 (24-72). Of the cases, 19 were female and 11 were male, 18 of them were operated on the right eye and 12 on the left eye. The lower punctum images of the cases were recorded with spectral domain anterior segment OCT preoperatively and at the 1st day, 1st month and 6th month after explantation of the silicone tube. In the lower punctum, external punctal width(EPW) and canaliculi depth (CD) were measured. RESULTS: The mean EPW and CD measurements of the cases in the preoperative period, respectively; 544.90±144.11 µm and 451.70±197.45 µm. First day after silicone tube explantation, EPW was 818.00±186.83 µm and CD was 735.35±337.15 µm, at 1st month EPW was 665.95±142.12 µm and CD was 619.30±212.11 µm and at 6th months EPW was 530±150.29 µm and CD was 558.45±254.37 µm, respectively. Mean EPW values were found to be higher on the first day after extubation than before surgery (p = 0.001). There was no significant difference in the mean EPW values at the first and sixth months after extubation compared to pre-implantation (p>0.05). The mean CD values were higher at the 1st day, 1st month and 6th month after tube explantation than preoperative CD values, they were not statistically significant. CONCLUSIONS: According to the lower punctum OCT imaging data, silicone tube implantations applied to the canalicular system do not create a structurally significant difference in the lower punctum. The punctal opening gradually decreases after extubation. The decrease in EPW values is more pronounced than the decrease in CD values. Silicone tube implantation was more effective in maintaining canaliculi depth compared to external punctal diameter.

Role of the MyD88 Dependent Pathway in Degenerative Disc Disease.

AIM: To define the substantial role of the TLR4 signaling pathway in the MyD88-dependent pathway, and to evaluate the results of TLR4 activation in nucleus pulposus cells. Moreover, we aim to associate this pathway with intervertebral disc degeneration and magnetic resonance imaging (MRI) findings. Additionally, the clinical differences among patients and the effects of their drug use will be evaluated. MATERIAL AND METHODS: Eighty-eight adult male patients with lower back pain and sciatica underwent MRI studies, which showed degenerative changes. Disc materials were obtained intraoperatively from those who underwent surgery for lumbar disc herniation. These materials were kept in freezers at ?80°C without any delay. Then, the collected materials were examined using enzyme-linked immunosorbent assays. RESULTS: Modic type I degeneration had the highest values of all markers, whereas Modic type III degeneration had the lowest values. These results verified that this pathway plays an active role in MD. Moreover, contrary to the current knowledge on which Modic type inflammation is more dominant, we showed that it is the Modic type I phase. CONCLUSION: The most intense inflammatory process was observed in Modic type 1 degeneration, and the MyD88-dependent pathway was found to play a key role. While the most intense molecular increase was detected in Modic type 1 degeneration, the lowest levels were observed in Modic type III degeneration. It has been observed that the use of nonsteroidal anti-inflammatory drugs affects the inflammatory process through the MyD88 molecule.

Can TRIF/TICAM-1 Dependent Pathway be Target Pathway in Lumbar Intervertebral Disc Degeneration?

AIM: To elucidate the role of the TIR-domain-containing adaptor-inducing interferon-? (TRIF) dependent pathway in intervertebral disc degeneration (IVD). MATERIAL AND METHODS: A total of adult male patients with low back pain (LBP) (+/- radicular pain) were further evaluated by magnetic resonance imaging (MRI) with surgical indication for microscopic lumbar disc herniation (LDH). Preoperatively, patients were classified according to Modic Changes (MC), nonsteroidal anti-inflammatory drugs (NSAIDs) use, and the presence of radicular pain in addition to the LBP. RESULTS: The age of the 88 patients ranged from 19 to 75 years (mean: 47.3 ± 19.6 years). Twenty eight of the patients were evaluated as MC I (31.8%), 40 as MC II (45.4%), and 20 as MC III (22.7%). The majority of patients (81.8%) had radicular LBP, while 16 patients (18.1%) had only LBP. Predominantly, 55.6% of all patients were taking NSAIDs. Levels of all adaptor molecules were highest in the MC I group and lowest in the MC III group. The levels of IRF3, TICAM1, TICAM2, NF-kB p65, TRAF6, and TLR4 were significantly increased in the MC I group compared to the MC II and MC III groups. The variations of the individual adaptor molecules showed no statistically significant difference in the use of NSAIDs and radicular LBP. CONCLUSION: As a result of the impact assessment, the current study clearly demonstrated for the first time that the TRIFdependent signalling pathway plays a crucial role in the degeneration process in human lumbar intervertebral disc specimens.

The Protective Effects of Thymosin-ß-4 in a Rat Model of Ischemic Acute Kidney Injury.

BACKGROUND: Despite the progress in the treatment of acute kidney injury (AKI), current curative approaches fail to provide adequate treatment. In this study, we aimed to investigate the possible protective effects of thymosin-ß-4(Tß4) on an ischemic AKI model in rats. METHODS: Rats were randomly assigned into four groups (n = 8/group): The control group (sham-operated), the ischemia-reperfusion (I/R) group; renal ischemia (90 min) by infrarenal abdominal aortic occlusion followed by reperfusion (3 h), the Tß4 + I/R group; treated with Tß4 before I/R, and the I/Tß4/R group; treated with Tß4 just before reperfusion. Besides renal function determination (creatinine (Cr) and blood urea nitrogen (BUN)); histological evaluation was also conducted. Renal tissue caspase-9, matrix metalloproteinase (MMP-9) activities, and hyaluronan levels were measured. Additionally, renal tissue oxidative stress (lipid hydroperoxide, malondialdehyde, superoxide dismutase, glutathione, pro-oxidant-antioxidant balance, ferric reducing antioxidant power, nitric oxide), inflammation (tumor necrosis factor-α, interleukin-1ß, interleukin-6, nuclear factor-κß) were evaluated. RESULTS: I/R increased the level of caspase-9, MMP-9 activity, and hyaluronan (p < 0.001) and these were significantly decreased in both Tß4 groups. Moreover, I/R led to increases in oxidative stress and inflammation parameters (p < 0.001) while the levels of antioxidants were decreased. Nevertheless, Tß4 in both groups were able to restore oxidative stress and inflammation parameters. Furthermore, Tß4 attenuated histologic injury caused by I/R (p < 0.01) and diminished serum urea-creatinine levels (p < 0.001). CONCLUSION: These results suggest that Tß4 has significant improving effects in ischemic acute kidney injury. This beneficial effect might be a result of the inhibition of extracellular matrix remodeling and apoptosis cascade via modulation in renal redox status and inflammation.

Comparative Analysis of NF-κB in the MyD88-Mediated Pathway After Implantation of Titanium Alloy and Stainless Steel and the Role of Regulatory T Cells.

OBJECTIVE: Development of immunologically smart implants, integrated to biological systems, is a key aim to minimize the inflammatory response of the host to biomaterial implants. METHODS: The aim of this study is to investigate the influence of titanium alloy and stainless steel implants on immunological responses in rats by comparative analysis of nuclear factor kappa B (NF-κB) profiles in the activation of inflammatory signaling pathways and the role of CD4+CD25+Foxp3+. RESULTS: Both Ti alloy and stainless steel alloy group implantation affect Toll-like receptors-4 pathways and CD4+CD25+ regulatory T cells in different ways. CONCLUSIONS: Results show that NF-κB/p65 and NF-κB1/p50 possess potential as a therapeutic target in the prevention of adverse reactions to metal, especially for controlling inflammation after the implantation.

Protective Effect of Thymosin ß4 against Abdominal Aortic Ischemia-Reperfusion-Induced Acute Lung Injury in Rats.

Background and objectives: Ischemia-reperfusion (IR) caused by infrarenal abdominal aorta cross-clamping is an important factor in the development of ischemia-reperfusion injury in various distant organs. Materials and Methods: We investigated potential antioxidant/anti-inflammatory effects of thymosin beta 4 (Tß4) in a rat model of abdominal aortic surgery-induced IR. Tß4 (10 mg/kg, intravenous (i.v.)) was administered to rats with IR (90-min ischemia, 180-min reperfusion) at two different periods. One group received Tß4 1 h before ischemia, and the other received 15 min before the reperfusion period. Results: Results were compared to control and non-Tß4-treated rats with IR. Serum, bronchoalveolar lavage fluid and lung tissue levels of oxidant parameters were higher, while antioxidant levels were lower in the IR group compared to control. IR also increased inflammatory cytokine levels. Tß4 reverted these parameters in both Tß4-treated groups compared to the untreated IR group. Conclusions: Since there is no statistical difference between the prescribed results of both Tß4-treated groups, our study demonstrates that Tß4 reduced lung oxidative stress and inflammation following IR and prevented lung tissue injury regardless of timing of administration.

Oxidative stress in lymphoid tissues and complement activation in alcoholic mother rats and their newborns.

Pregnant Wistar rats were exposed to ethanol under chronic conditions using the gavage method to assess the complement activation and effects of oxidative stress on fetus lymphoid organs and liver. The effects were monitored on both the 10th (G10) and the 30th (G30) day of the offspring of alcoholic mother rats. Maternal ethanol caused a significant decrease in the glutathione level, whereas malondialdehyde and carbonyl levels increased in the liver and lymphoid tissues. Na+,K+-ATPase, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase activities in these organs also decreased. Furthermore, complement C3 and C5 activities of G10 and G30 groups were significantly higher compared with those of the control group. In conclusion, the results demonstrated that alcohol was capable of triggering damage to the membranes of the liver and lymphoid tissues of G10 and G30 groups, and C3 and C5 contributed to the development of alcohol-induced fetal tissue injury.

Which is better Stainless Steel or Titanium alloy?

AIM: To investigate immunologic reactions after implantation of stainless steel (SS) alloy and titanium (Ti) alloy in a rat model. Macrophage and cytokine responses have been reported after the in vivo and in vitro application of different biomaterials. MATERIAL AND METHODS: Wistar albino rats after an exploration of the thoracolumbar paravertebral muscle tissue of the subjects, group I underwent a sham surgery, and groups II and III were implanted Ti alloy and SS alloy rods respectively. The CD4, CD8, CD25 (IL-2R) (lymphocyte and CD4 gate), CD4+CD8+ and CD4+CD25+Foxp3+ (Tregs), IL-4, IL-10, IL-6, IL-17A, TGF-ß, TNF-α in the blood were analyzed. RESULTS: CD4, CD25 (IL-2R), CD4+CD8+ and Tregs levels were lower in the Group III compared to the sham and Group IIs. IL-6, IL-17A, TGF-ß and TNF-α levels in the G III showed a significant increase on all days in comparison with the sham and Group II. IL-4 and IL-10 levels, were lower in the Group III than those in the Group II; and a significant decrease was observed in the IL-10 level. While there was a reduction in IL-6 and IL-17A levels in the Group II as opposed to the sham group. CONCLUSION: As opposed to SS alloy, Ti alloy suppresses the development of inflammations by inhibiting proinflammatory response; strengthens the humoral immune system by intensifying the antibody-dependent immune response; triggers the development of immune tolerance by regulating the immune response; and activates the mechanism that prevents immune response-related damage from occurring.

Comparative Analysis of Tear Film Levels of Inflammatory Mediators in Contact Lens Users.

PURPOSE: To compare tear films levels of various inflammatory cytokines in asymptomatic contact lens (CL) users. CL users of rigid gas-permeable CLs (RGPCL) (group 1) or silicone hydrogel CLs (SiHCL) (group 2) were compared with non-CL-using healthy subjects (group 3). MATERIALS AND METHODS: Tear samples were collected from subjects in each group after ensuring that there were no complications secondary to CL wear in the CL-wearing participants. Tear-film levels of interleukins (ILs)-1ß, -6, and -8; granulocyte-macrophage colony-stimulating factor (GM-CSF) (using the Luminex method); and leukotriene B4 (LTB4) (using the ELISA method) were determined. Cytokine levels were compared among the three groups using analysis-of-variance (ANOVA) and Kruskall-Wallis tests. RESULTS: There were significant differences in concentrations of IL-1ß, GM-CSF and LTB4 among the three groups (p = 0.002, p = 0.021 and p = 0.009, respectively), as shown by the Kruskall-Wallis test comparing all three groups for the three cytokines. There were no significant differences for IL-6 and IL-8 (p = 0.079 and 0.094, respectively) when all three groups were compared. CONCLUSIONS: There were substantial statistically significant differences between RGPCL users, SiHCL users and control subjects in levels of tear film cytokines. Although CL users were asymptomatic, changes in tear-film levels of several important inflammatory mediators revealed that a chronic inflammatory process occurs during CL wear.

How analgesia-sedation alters monocyte mCD14 and HLA-DR levels in patients undergoing cerebral angiography?

AIM: This study aims to evaluate how analgesia-sedation causes alterations of HLA-DR and cytokines (IL-10 and IL-6) in patients undergoing cerebral angiography for several cerebral vascular diseases. MATERIAL AND METHODS: This study includes 41 males who underwent cerebral angiography. The study sample was divided into two: Group I had 7 patients who did not receive and group II had 34 patients who received analgesia-sedation before cerebral angiography. A venous blood sample was collected before and after cerebral angiography. RESULTS: Analgesia-sedation caused significant increase CD4+ and CD19 T lymphocytes (p < 0.001) but group I showed significant increase in CD40, CD154, and MHC-II levels (p < 0.001) after cerebral angiography. CONCLUSION: We suggest that the effects of fentanyl and midazolam on the immune response are the reflection of the effects by the monocyte, mHLA-DR expression. In the future, depending on the immunological status of the patients, different anesthetic applications including the new anesthetic agents that will be able to decrease immune system suppression will be required.

TH1 and TH2 Cytokines Production and NK Cell Level Assessment in Peripheral Blood of Patients with DDH.

In this study, our aim is; if the studies will quide us in peripheral blood, for the changes in inflammatory cytokine levels we defined before DDH tissue. Twenty-six patients were suggestive of lumbar DDH were included in this study. Control subjects included 14 autopsy cases. From each patient, disc tissues and peripheral blood samples for plasma were collected during the surgery. For the controls, disc samples and blood for plasma by intracardiac puncture were obtained during autopsy. The Flow Cytometry was used to obtain the lymphocyte CD56 (NK). The Luminex was used to obtain IL-2, IL-4, IL-10, IL-12, IFN-gamma, in both plasma and disc tissues. The results were compared between the two groups. Comparing the two groups regarding plasma demonstrated that IL-2, IL-4, IL-12, IFN-gamma were significantly higher than in patients than those of the controls. Likewise, tissue levels of IL-2, IL-4, IL-10, IL-12, TNF-alpha, CD56 were found to be significantly higher in the patients. With respect to the comparison between the plasma disc samples in the patients, plasma showed significant higher levels of IL-2, IL-12 on the other hand IL-4 was found to be significantly higher in the disc samples. Findings suggest that only tissue samples responses in occurring but not blood samples. We don't think our results in peripheral blood will guide us specifically in DDH.

Comparison of deep anterior lamellar keratoplasty and intrastromal corneal ring segment implantation in advanced keratoconus.

PURPOSE: To compare the visual and refractive results in eyes with advanced keratoconus having deep anterior lamellar keratoplasty (DALK) with those having intrastromal corneal ring segment (ICRS) implantation. SETTING: Dr. Lütfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey. DESIGN: Comparative case series. METHODS: Records of advanced keratoconus patients with a clear central cornea and contact lens intolerance who had DALK or ICRS implantation were reviewed. Preoperatively and after 24 months, the uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, and Orbscan II keratometry (K) readings in the 2 groups were comparable. RESULTS: The DALK group comprised 36 eyes and the ICRS group, 30 eyes. Both groups had a statistically significant increase in UDVA and CDVA from preoperatively to 24 months postoperatively (P<.001). The DALK group had a statistically significantly greater improvement in UDVA and CDVA than the ICRS group 24 months postoperatively (P<.001). The improvement in spherical equivalent (SE) refractive error, manifest sphere, and manifest cylinder was statistically significant in both groups (P<.001). The mean reduction in SE and manifest cylinder were significantly greater in the DALK group (P<.05). The postoperative reduction in the maximum and minimum K values was statistically significant in both groups (P<.001); the mean reduction in K values was significantly greater in the DALK group (P<.001). CONCLUSION: Although DALK provided greater improvement in visual acuity and refractive errors in advanced keratoconus cases, ICRS implantation may be an alternative treatment with satisfactory outcomes and less visual impact.

Corneal endothelium after deep anterior lamellar keratoplasty and penetrating keratoplasty for keratoconus: a four-year comparative study.

PURPOSE: To compare the status of corneal endothelium and central corneal thickness within the first four postoperative years after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK) in patients with keratoconus. MATERIALS AND METHODS: Thirty-nine eyes (Group A) which had PK and 44 eyes (Group B) which had DALK for the treatment of keratoconus were included in this retrospective study. The endothelial cell density (ECD), the mean endothelial cell area and the coefficient of variation of cell area were assessed with a non-contact specular microscope, and the central corneal thickness (CCT) was measured with an ultrasound pachymeter. RESULTS: Mean ECD loss rate at two years was 36.24% in Group A and 18.12% in Group B (P<0.001). Mean ECD loss rate at four years was 47.82% in Group A and 21.62% in Group B (P<0.001). Mean annual ECD loss rate was calculated 14.12% per year in Group A and 5.78% per year in Group B. In the PK group, increase in mean CCT was 15.60% in two years and 15.03% in four years, while in the DALK group, mean CCT increased by 8.05% in two years and 9.31% in four years. CONCLUSIONS: As the majority of ectatic disorders such as keratoconus occur in young people, long-term endothelial cell survival following treatment with keratoplasty is essential for the long-term visual ability. Our finding that corneal endothelial cell loss in the DALK group occurs at a slower rate than in the PK group suggests DALK as a safer alternative to PK in these selected patients.

The effects of analgesia-sedation on the immune system before and after cerebral digital subtraction angiography.

AIM: Cerebral digital subtraction angiography (DSA) is an invasive procedure and may cause inflammatory responses in the body. This study aims to provide cytokine and lymphocyte profile in a population of patients underwent cerebral DSA. MATERIAL AND METHODS: Forty-one male patients who admitted for cerebral DSA were included in this study. Patients were divided into two groups: Group I (n = 7) included patients who did not receive analgesia-sedation and group II (n = 34) received analgesia-sedation before procedure. For the molecules, a venous blood samples from every patient was collected before and after cerebral DSA. RESULTS: Cytokine levels in group I showed a trend to increase in the majority of the molecules after the procedure except IL-1ß. In group II, cytokines showed variable trend. When comparing the two groups regarding cytokine levels after cerebral DSA, IL-1ß, IL-10, IL-12, and IFN-γ levels increased significantly in group II. Comparing the two groups with respect to lymphocytes after cerebral DSA showed that CD56 levels were significantly higher in group II and other parameters did not show significant differences. CONCLUSION: It can be possible that delimitation of the action(s) of the cytokines affecting the secretion or activation of CD56 (natural killer) may avoid complications of inflammation after invasive procedures.

Relationship between lymphocytes, IL2 and the hormones E2, LH, PRG and FSH in menopausal and postmenopausal women.

PROBLEM In this baseline study, our aim is to show the relationship of parameters and gonad hormones in menopausal and postmenopausal women. METHOD Blood samples were taken from menopausal and postmenopausal women (12-14 months and ≥10 years, respectfully, since their last menstruation). Adolescents aged 13.7 ± 0.7 were used as controls. Hormones were measured by ELISA and percentages of CD45, CD4, CD8, CD3, CD19, IL-2, CD25 and HLA-DR were measured by flow cytometry. RESULTS Both groups showed an increase in the percentage of CD3, CD4 and CD8. Levels of CD19 were significantly lower in the postmenopausal group. However, changes in immunologic parameters during menopause were less marked than the hormonal changes observed in these groups. Most of the correlations LH × CD3 (-ve), LH × IL2R (-ve) and E2 × CD19 (+ve) suggesting how menopausal women with particularly high LH or low E2 levels may be affected. Only CD3 and HLA-DR correlated with the hormonal changes in the postmenopausal group. IL-2 levels were high in the menopausal group and low in the postmenopausal group; however, no correlation was observed. DISCUSSION Menopause is characterized by increased levels of IL-2, which has critical immune-modulatory effects. These changes may be related to the overall hormonal change process observed during menopause.

Catabolic cytokine expressions in patients with degenerative disc disease.

AIM: Lumbar degenerative disc disease (DDD) is a common disease of advanced age characterized by progressive changes in the intervertebral disc and associated structures. There have been great efforts for years to explain its pathophysiological mechanism(s). This study aims to provide cytokine profile and in addition to the lymphocytes in a population of patients with lumbar DDD. MATERIAL AND METHODS: Twenty-six patients whose clinical and radiological features were suggestive of lumbar DDD that underwent surgery and 14 autopsy cases as control were included. Patient disc samples were obtained during surgery whilst disc materials were collected during autopsy procedures from the controls. Major cytokines and lymphocytes were studied by using the flow cytometry method. RESULTS: Significantly higher levels in disc samples in relation to IL-1ß, IL-2, IL-4, IL-10, IL-12, TNF-α, CD8, CD56, CD19, and CD40 were found in the patients compared to the controls. Positive correlations were shown between CD3/CD4, CD25/CD3, CD25/CD4, CD19/CD4 but negative correlations were shown between CD19/CD3 and CD25/CD19 in both groups. CONCLUSION: The findings suggest that both local inflammatory responses occur in lumbar DDD. Using specific cytokines either by local or systemic application may reverse the degenerative process.

HSP-10 in ovarian cancer: expression and suppression of T-cell signaling.

OBJECTIVE: Suppressed T-cell activation is a hallmark of advanced ovarian cancer. Studies in pregnancy have demonstrated similar T-cell dysfunction mediated, at least in part, by HSP10, identified as "early pregnancy factor." This pilot study addresses the presence of HSP10 in the circulation of ovarian cancer patients and assesses its role in suppressing CD3-zeta. METHODS: Sera were obtained from ovarian cancer patients (n = 10) and age-matched noncancer-bearing female controls (n = 9). HSP10 presence was determined semiquantitatively by Western immunoblotting in sera, ascites, and ovarian tumor cell conditioned media. The consequences of HSP10 on CD3-zeta suppression were defined using a Jurkat cell bioassay, using unfractionated patient sera, sera with HSP10 removed by immunoprecipitation and the immunoprecipitate. RESULTS: HSP10 was detected in both sera and ascites of patients with ovarian cancer; however, it was not detectable in controls. HSP10 was also detected in the culture media of ovarian tumor cells. Sera containing HSP10 suppressed T-cell CD3-zeta expression, which correlated with HSP10 levels (r2 = 0.839). When HSP10 was removed from the sera, the ability to suppress CD3-zeta was diminished and the immunoprecipitated material was capable of suppressing CD3-zeta. CONCLUSIONS: HSP10 appears to be produced and released from ovarian tumor cells and is detectable in the peripheral blood and ascites of patients. This circulating HSP10 appears to suppress T-cell expression of CD3-zeta, a key component of T-cell activation. Our findings indicate that, as in pregnancy, production and release of HSP10 may be a critical factor in the suppression of T-cell activation, allowing the tumor to escape immune surveillance.