Dynamic disulfide/thiol homeostasis in lead exposure denoted by a novel method.

Lead is a toxic heavy metal, and prevention of human exposure to lead has not been accomplished yet. The toxicity of lead is continually being investigated, and the molecular mechanisms of its toxicity are still being revealed. In this study, we used a novel method to examine thiol (SH)/disulfide homeostasis in workers who were occupationally exposed to lead. A total of 80 such workers and 70 control subjects were evaluated, and their native and total SH values were measured in serum using a novel method; their blood lead levels were also assessed. The novel method used for SH measurements was based on the principle of measuring native SH, after which disulfide bonds were reduced and total SHs were measured. These measurements allowed us to calculate disulfide amounts, disulfide/total SH percent ratios, disulfide/native SH percent ratios, and native SH /total SH percent ratios. We found that disulfide levels were significantly higher in workers who were exposed to lead (21.08(11.1-53.6) vs. 17.9(1.7-25), p < 0.001). Additionally, the disulfide/native SH and disulfide/total SH percent ratios were higher in exposed workers, while the native SH/total SH percent ratios were higher in the control subjects. Furthermore, the lead and disulfide levels showed a positive correlation, with p < 0.001 and a correlation coefficient of 0.378. Finally, the novel method used in this study successfully showed a switch from SH to disulfide after lead exposure, and the method is fully automated, easy, cheap, reliable, and reproducible. Use of this method in future cases may provide valuable insights into the management of lead exposure.

An evaluation of thiol/disulphide homeostasis in patients with psoriasis.

INTRODUCTION: The role of oxidative stress in the pathogenesis of psoriasis has been investigated in previous studies with conflicting results. On the other hand, well-established treatments currently used in psoriasis exert their effects via a boost of oxidative stress. Recently, a strong positive association between psoriasis, metabolic syndrome and dyslipidemia has also been described showing the complex nature of the disease. AIM: To examine thiol/disulphide homeostasis, a newly developed homeostasis assay in psoriasis and evaluate the possible association between thiol/disulphide homeostasis and dyslipidemia in psoriasis. MATERIAL AND METHODS: The study population included 92 psoriasis patients and 71 healthy subjects. Serum native thiol, total thiol and disulphide levels were investigated in patients with psoriasis and in healthy subjects. In addition, lipid profile (serum total cholesterol, triglyceride, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) levels were investigated in both groups. The association between thiol-disulphide parameters and dyslipidemia was also evaluated. RESULTS: Serum total cholesterol and triglyceride levels were found to be higher in patients with psoriasis than in the healthy group. Lower plasma disulphide and higher native thiol levels were found in patients with psoriasis indicating an antioxidant status. CONCLUSIONS: To our knowledge, this is the first study showing the shift of dynamic thiol/disulphide homeostasis towards the thiol form in psoriasis which indicate higher antioxidant status.

Comparison of E-selectin and the other inflammatory markers in lumbar disc herniation: a new promising therapeutical window for radicular pain.

STUDY DESIGN: Histopathologic and immunohistochemical analysis of the herniated disc specimens obtained from 50 patients who had unilateral persistent radicular pain or unilateral radicular motor paresis. OBJECTIVE: The aim of this study was to investigate the prevalence of inflammatory cells in lumbar disc herniations (LDH) and compare the prevalence of leukocyte adhesion protein "E-selectin" with other inflammatory cells such as T cells, B cells, and macrophages. SUMMARY OF BACKGROUND: Studies on inflammatory cells and biochemical mediators of inflammation have suggested that these factors may play an important role in pathophysiology of radicular pain, and the medical therapy was formed against to block these cells and inflammatory cytokines. METHODS: The herniated disc specimens obtained from 50 patients who had unilateral persistent radicular pain or unilateral radicular motor paresis were microscopically examined after staining with monoclonal antibodies of CD20, CD45, CD68, and E-selectin. Relative risk assessment of the straight-leg raising (SLR) test positivity or negativity with CD20, CD45, CD68, and E-selectin staining was investigated. RESULTS: Our data emphasize that, the cases with positive SLR test had higher rates of immunostaining with E-selectin and CD45. There were no statistically significant relationship between SLR positivity and CD20 and CD68. CONCLUSIONS: We suggest that E-selectin is as valuable as the other well-known inflammatory markers in the pathogenesis of LDH. In our opinion, beside the well-known nonsteroidal anti-inflammatory drugs, antagonists targeting E-selectin can be potentially effective therapeutics for controlling inflammation in LDH.

Serum IL-17 levels in patients with rosacea.

BACKGROUND: Rosacea is a chronic inflammatory skin disease characterized with increased serum and tissue inflammatory mediators. IL-17 is a well-known inflammatory mediator that plays important roles in pathogenesis of inflammatory skin diseases. Previous studies reported that Th17 pathway is activated in rosacea and IL-17, one of Th17 signature cytokines, is elevated in tissue samples of rosacea patients. OBJECTIVES: The aim of this study was to investigate serum IL-17 levels in rosacea patients and to study its relationship with disease characteristics. METHODS: Sixty patients diagnosed with rosacea and 60 healthy controls were included in the study. Serum IL-17 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean serum IL-17 level was 8.03 pg/mL (SD = 1.47) in rosacea patients and 7.37 pg/mL (Sd = 1.19) in controls. Serum IL-17 levels were significantly higher in rosacea (p = 0.002). Serum IL-17 levels were similar among patients with erythematotelangiectatic (ET) and papulopustular (PP) rosacea (8.02 vs 8.06, p = 0.83). Serum IL-17 levels did not correlate with rosacea severity (p = 0.59, r = 0.07 in ET rosacea; p = 0.88, r = 0.02 in PP rosacea), age of onset (p = 0.58, r = -0.07), and disease duration (p = 0.37, r = -0.11). Primary features and global assessments did not correlate with serum IL-17 levels (all p > 0.05). Among secondary features, edema showed a significant negative correlation with serum IL-17 concentrations (p = 0.037, r = -0.26). CONCLUSIONS: Our study showed increased serum IL-17 levels in rosacea patients and a significant correlation between IL-17 concentrations and secondary features of the disease suggesting IL-17 may contribute to pathogenesis of rosacea and may be a new target for rosacea treatment.

Telogen effluvium in daily practice: Patient characteristics, laboratory parameters, and treatment modalities of 3028 patients with telogen effluvium.

BACKGROUND: Telogen effluvium (TE) is a common form of non-scarring alopecia, characterized by excessive shedding of telogen club hairs. OBJECTIVES: The aim of the present study was to investigate patient characteristics, laboratory parameters, and treatment strategies in TE. METHODS: Electronic records of 3028 patients were retrospectively analyzed. Demographic and clinical data, as well as serum parameters screening for iron, vitamin B12, vitamin D, folate and zinc deficiencies, thyroid function, and ANA titers, were evaluated. RESULTS: In the study group, the most frequently performed test type was serum ferritin level (82.3%), followed by complete blood count (81%), both of which revealed that 6.2% of the patients had iron deficiency anemia. 4.6% of the patients had thyroid dysfunction. In screened patients, vitamin and mineral deficiencies were as follows: vitamin D (72.2%), vitamin B12 (30.7%), folate (4.4%), and zinc (2.1%). Women were more likely to be prescribed vitamin D replacement therapy. Iron replacement was the most frequently ordered treatment, comprising 37.5% of total prescriptions. CONCLUSION: To the best of our knowledge, this is the most comprehensive retrospective study having the largest number of patients with TE. Our results will not only help to augment knowledge about TE, but also provide a diagnostic algorithm for the laboratory and clinical workup of patients with TE.

Evaluation of HLA class I and HLA class II allele profile and its relationship with clinical features in patients with alopecia areata: a case-control study.

BACKGROUND: Alopecia areata (AA) is an autoimmune disease where autoimmune dysregulations along with genetic susceptibility are hypothesized to play a role in pathogenesis. OBJECTIVE: The aim of this study in to evaluate HLA-A, HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 profile and its relationship with clinical features in AA patients. MATERIALS AND METHODS: Ninety-eight patients with AA and 100 healthy controls were included in the study. HLA-A, HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 frequencies were analyzed using polymerase chain reaction-sequence specific primers (PCR-SSP). RESULTS: HLA-B*39 and HLA-HLA-DRB1*15 allele frequencies were increased (p = .022 and p = .023, respectively), HLA-A*11 and HLA-B*35 frequencies were decreased (p = .006 and p = .014, respectively) in AA patients. HLA-B*13 and HLA-DRB1*11 were associated with poor prognostic factors. A class I allele, HLA-B*13 was associated with recurrence (p = .023) and presence of nevus flammeus (p = .022), while the class II allele HLA-DRB1*11 was associated with widespread hair loss (diffuse or universal alopecia) (p = .026), presence of ophiasis (p = .049) and juvenile onset (p = .018). CONCLUSION: Belonging to two different classes of HLA family, HLA-B*13 and HLA-DRB1*11 alleles identified separate set of risk factors. In addition to increasing the risk of AA, HLA alleles may affect the prognosis of the disease.

Posterior epidural mass: can a posteriorly migrated lumbar disc fragment mimic tumour, haematoma or abscess?

A 60-year-old woman complained of low back pain radiating to both buttocks and to the anterior aspect of the left thigh. MRI showed a left posterolateral epidural mass at the L1-L2 level. An epidural abscess was suspected, but the biochemistry was normal. Excision yielded complete relief of symptoms. Pathological examination demonstrated that the specimen was a migrated disc fragment. The authors found 29 other cases of disc migration to the posterior epidural space; two of these were at the thoracic level. Eleven of the 27 lumbar cases (40%) were complicated with Cauda Equina Syndrome (CES). MRI is the method of choice to make the diagnosis. The differential diagnosis includes tumour, haematoma and abscess.

Parkinsonian syndrome associated with subacute subdural haematoma and its effective surgical treatment: a case report.

There have been several reports of parkinsonian syndrome arising from a mass effect from subdural haematomas. In this study, we present a case of parkinsonian syndrome caused by a subacute subdural haematoma. Evacuation of the haematoma resulted in the disappearance of parkinsonian symptoms in this case. Parkinsonism is not common complication of subdural haematoma; surgical treatment of those cases is associated with favourable outcome, without the need for antiparkinsonian medication.

An unusual cause of low back pain: paravertebral muscle metastases of lung cancer.

Paravertebral muscle metastasis is an extremely rare cause of low back pain. Lipomas, haemangiomas, hibernomas and liposarcomas should be considered first in the aetiology of paravertebral muscle masses. Schwannoma, neurofibroma, ganglioneuroma and paraganglioneuromas that show contiguous spread should also be included in the differential diagnosis. Haematogenous metastases are most frequently caused by lung cancers. Lung cancers typically metastasize to liver, brain, bone, kidney, and adrenal glands. They rarely metastasize to skeletal muscles due to metabolism, high tissue pressure and blood flow of muscles. Our case was a 48-year-old male who had been smoking 40 cigarettes per day and presented to our clinic with low back pain and a mass in the lower back region. The mass in his lower back region was excised and histopathological examination confirmed metastasis of a neuroendocrine tumour. Further examinations revealed the lung as the primary source of the metastasis.

Spontaneous primary intraventricular hemorrhage in adults: clinical data, etiology and outcome.

AIM: Primary intraventricular hemorrhage (PIVH), bleeding in the ventricular system without a recognizable parenchymal component, is a rare neurological disorder. The purpose of this study was to identify clinical features, risk factors, etiology and outcome of patients with PIVH. MATERIAL AND METHODS: We retrospectively reviewed the clinical data, complementary examinations, outcome and computed tomography (CT) IVH score of 24 patients in our hospital from 2004 to 2008. We identified 24 patients with the inclusion criteria of non-traumatic PIVH. Their mean age was 60.6+/-17.4 years (range 38-79). Fourteen patients were male and 10 were female. RESULTS: The major symptoms included headache (n=24), loss of consciousness (n=6), confusion and disorientation (n=14), nausea/vomiting (n=10). Angiography revealed vascular malformations in five patients (21%). Other possible causative factors were hypertension in 12 patients (50%) and clotting disorder in one. The aetiology remained unknown in six patients. Most PIVH patients had associated hydrocephalus (58%) and 37% of the patients required ventricular drainage. In-hospital mortality was high (41%) and a FOUR score

Research on the Balance of Thiol-Disulfide in Blood Serum in Women with Telogen Effluvium.

BACKGROUNDS: Telogen effluvium (TE) is the most common reason for hair loss in humans. Although the exact etiopathogenesis of TE has not been revealed clearly and completely, multifactorial etiologies are to be blamed. In recent years, since oxidative stress (OS) has been shown to play an important role in the etiopathogenesis of so many diseases, the effects of OS on several skin diseases are researched and analyzed. Thiols are antioxidant components that include sulfur group, and the balance of thiol-disulfide has an important role in the formation and prevention of OS. This balance is destroyed in many diseases and its effect on TE is not clearly understood yet. OBJECTIVES: In this study, we aimed to search the thiol-disulfide balance that could reveal OS in patients with TE. MATERIALS AND METHODS: Fifty-two patients with TE and control group of 46 persons were included in the study. Native thiol, disulfide, and total thiol levels were evaluated by a new, automatic spectrophotometric method. Disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol rates were calculated. RESULTS: There was no statistical difference between TE patients and control group in terms of native thiol, disulfide, and total thiol levels. Thiol-disulfide balance was fixed and not affected in TE patients.

A non-bleeding complex intracerebral giant aneurysm case: case report.

An intracranial aneurysm with a diameter larger than 25 mm is considered a giant aneurysm (GA), and represent about 3-5% of all aneurysms. They are divided into two forms, specifically saccular and fusiform. Fusiform aneurysms are rare, making up only 1% of all intracranial aneurysms. They frequently involve the internal carotid artery (ICA) or the basilar or vertebral arteries, and rarely bleed. Treatment of huge aneurysms that have not bled is still controversial. Unlike the saccular huge aneurysms that lead to death of 80% of the patients few years after diagnosis, fusiform huge aneurysms, particularly those presenting with mass effect, have a better prognosis. In this manuscript, we discuss the infrequently seen intracranial fusiform giant aneurysms in light of the pertinent literature.

Endovascular treatment of primary infectious aneurysm in childhood: a case report.

Infectious aneurysms constitute 4% of all intracranial aneurysms. The microorganisms responsible are most commonly streptococcus viridans, staphylococcus aureus and combined bacterial infections. Nonetheless, cases with no reproduction in their cultures are rather frequent. A 6-year-old patient admitted with complaints of sudden headache, nausea, vomiting and high temperature. Intracerebral hematoma and saccular aneurysm located at the distal posterior cerebral artery were diagnosed as a result of the laboratory investigations and neuroradiological examinations. Infectious aneurysm was considered due to the clinical findings, morphology and location of the aneurysm. Although the causative microorganism was detected in blood culture, no focus could be detected. The aneurysm was hindered by endovascular intervention. In this manuscript, we discuss the infrequently seen childhood infectious aneurysm in the light of the pertinent literature.

A rare case of massive NF1 with invasion of entire spinal axis by neurofibromas: case report.

Neurofibromatosis type-1 (NF1) is a type of phakomatosis inherited in an autosomal dominant fashion. Also called 'von Recklinghausen disease' or 'peripheral neurofibromatosis', it comprises 90% of all neurofibromatosis (NF) cases. It is characterized by multiple peripheral nerve sheath tumors of benign character called neurofibromas. Surgical intervention is indicated when myelopathy and motor losses develop in the case of paraspinal neurofibromas, which are frequently localized to the cervical and lumbar regions. The level of surgical intervention required should be carefully considered and should take into account neurophysiological tests of paraspinal neurofibroma cases that allow estimation of the risk that the neurofibromas will invade the complete spinal axis. The best results are obtained with patients showing minimal neurological deficits during the pre-operative period. Little improvement may be expected from the patients who develop complete transection syndrome during the postoperative period. In the present paper, we discuss an NF1 case in which paraspinal neurofibromas were observed along the complete spinal axis of a 32-year-old male patient who arrived at the clinic reporting increasingly intense pins and needles and weakness. We discuss the patient's diagnosis, treatment, and prognosis, and relate this case to the literature.

The role of standing flexion-extension radiographs for spondylolisthesis following single level disk surgery.

OBJECTIVES: Spondylolisthesis is the forward displacement of a lumbar vertebra relative to the adjacent vertebra, occurs as result degeneration or surgery and is a special type of lumbar instability. There is no consensus about which radiologic modality or findings truly reflect the lumbar instability and the exact incidence after single level disk surgery is unknown. METHODS: In this prospective study, we have included 90 patients who were operated by the same surgeon with single level disk herniation. We aimed at evaluating the post-operative lumbar spondylolisthesis, with flexion and extension lateral radiographs in addition to standard magnetic resonance imaging (MRI). RESULTS: We have seen spondylolisthesis in six of 90 cases with standing lateral flexion-extension radiographs, which were undefinable with MRI. Pain intensity and functional-economic rating scale (Prolo scale) were unremarkable. DISCUSSION: We have concluded that standing flexion-extension radiographs should be routinely combined in patients with failed back surgery syndrome and even if lumbar instability is clinically suspected, especially when conventional MR examination is normal. When the MR examination showed spondylolisthesis, standing flexion-extension radiographs could not give additional information.

CT and MRI findings in calvarial non-infectious lesions.

Differential diagnosis of the calvarial lesions is important in order to decide whether biopsy, surgical intervention, or follow-up is required for further management. In this pictorial essay on calvarial lesions, lytic or sclerotic patterns, contours of the lesions, calcifications, soft tissue components, inner and outer table localizations were evaluated with computed tomography (CT). On magnetic resonance imaging (MRI) signal characteristics and contrast enhancement of the lesion, relation to brain parenchyma and soft tissue were evaluated. CT scan is considered to be the best examination to characterize bone alterations whereas MRI depicts bone marrow abnormalities and invasion of adjacent tissues.

The effect of mexiletine on the level of lipid peroxidation and apoptosis of endothelium following experimental subarachnoid hemorrhage.

OBJECTIVE: The role of apoptosis in etiopathogenesis of vasospasm is not clearly understood yet. It is widely accepted that protection of the endothelial cells from the process of apoptosis could have beneficial effects on cerebral vasospasm after subarachnoid hemorrhage (SAH). Mexiletine blocks sodium and calcium channels and activates ATP-sensitive K(+) channels. Moreover, mexiletine is known to have potent antioxidant effects through inhibiting free-radical production. METHODS: Twenty-one rabbits were allocated into three groups randomly. Group I was sham operated group (n=7). SAH occurred but no medication was given to the Group II rabbits (SAH only group) (n=7). Mexiletine (50 mg/kg, b.i.d., i.p.) was administered just before SAH and continued until 48 hours following SAH to the Group III rabbits (Mexiletine treated group) (n=7). The ApopTag peroxidase in situ apoptosis detection kit (Serologicals Corporation, former Intergen) was used to demonstrate apoptosis in a cross section of basillary arteries. Thiobarbituric acid reactive material was used to determine the lipid peroxidation levels. RESULTS: There was a statistically significant difference between lipid peroxidation product levels of the control and SAH only groups (p<0.05). The level of lipid peroxidation production in Mexiletine treated group was significantly lower compared with SAH only group (p<0.05) but not significantly higher than the control group (p>0.05). DISCUSSION: In the present study we investigated the antioxidant action of mexiletine on apoptosis of endothelium following a rabbit SAH model. This experimental study directly suggested that lipid peroxidation is an important step in development of apoptosis in endothelial cells and prevention of structural integrity of endothelial cell should play a beneficial role in attenuation of cerebral vasospasm. Mexiletine treatment prevented the increase in lipid peroxidation and cerebral vasospasm. Examination of endothelial cells by staining specific for apoptosis demonstrated significant protection of cell integrity in the treated group.

Thiol/disulfide homeostasis: A prognostic biomarker for patients with advanced non-small cell lung cancer?

BACKGROUND: The aim of this study was to investigate oxidative stress and thiol/disulfide status with a novel automated homeostasis assay in advanced non-small cell lung cancer (NSCLC). METHODS: Thirty-five patients with advanced NSCLC, who had been newly diagnosed and previously untreated, and 35 healthy subjects were chosen for the study. We measured plasma total thiol (-SH+-S-S-), native thiol (thiol) (-SH), and disulfide (-S-S-) levels in the patients with NSCLC and the healthy subjects. The thiol/disulfide (-SH/-S-S-) ratio was also calculated. RESULTS: Statistically significant differences between the patient group and the control group were detected for the thiol/disulfide parameters. The mean native thiol, total thiol, and disulfide levels were significantly lower in the group with advanced stage NSCLC. The cut-off value was 313 and 13.8 for native thiol and disulfide, respectively. Median overall survival (OS) was significantly shorter in patients with low native thiol and disulfide levels according to the cut-off value (respectively, P = 0.001; P = 0.006). Native thiol, total thiol, and disulfide levels were correlated with Karnofsky performance status (KPS), OS, and age. Additionally, hierarchical regression analyses showed gender, KPS, lung metastases, and plasma native thiol levels were the determinants of OS in the final model. CONCLUSION: These results suggest that in advanced stage NSCLC, the native thiol, total thiol, and disulfide levels decrease, while the native thiol/disulfide ratio does not change. Low levels of thiol/disulfide parameters are related to tumor aggressiveness and may predict a poor outcome for patients with NSCLC.