Comparison of serum NO, TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels with grades of retinopathy in patients with diabetes mellitus

BACKGROUND: Vitreal interleukin (IL)-1beta (IL-1beta), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels have previously been determined in patients with proliferative diabetic retinopathy (PDR). However, at present there is no cohort study linking serum levels of NO and many inflammatory cytokines such as TNF-alpha, IL-1beta, soluble IL-2 receptor (sIL-2R), IL-6 and IL-8 to the grade of the microvascular complications. PURPOSE: To determine the relation between the stages of DR and the levels of serum NO, TNF-alpha, IL-1beta, sIL-2R, IL-6 and chemokine IL-8 in patients with diabetes compared with healthy controls. METHODS: Fifty-three consecutive patients with diabetes (25 men, 28 women) with or without DR and 15 non-diabetic healthy subjects (seven men, eight women) as controls were included in this prospective study. As an indicator for NO, serum total nitrite (NO2- + NO3-) levels (end-product of NO) were measured by the Griess reaction. Serum TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels were determined by a spectrophotometric technique using an Immulite chemiluminescent immunometric assay. The patients with diabetes were classified into three groups according to the stage of DR: no DR (NDR; n = 16), non-proliferative DR (NPDR; n = 18) and PDR (n = 19). The data were analysed using a Mann-Whitney U-test and the results were expressed as mean +/- SE (range). RESULTS: The levels of IL-1beta and IL-6 were below the detection limits of the assay (for each, <5.0 pg/ml) in all patients with diabetes and controls. Soluble IL-2R levels ranged from 260 to 958 U/ml, with the highest values observed in the patients with PDR. In 47 of the 53 samples (89%) tested for diabetic patients, IL-8 levels were above the detection limits of the assay (5.0 pg/ml). IL-8 levels ranged from <5.0 to 25.0 pg/ml, with the highest mean values observed in PDR patients. TNF-alpha was detectable in 46 of 53 patients with diabetes (87%), ranging from <4.0 to 26.4 pg/ml, with again the highest values obtained in the patients with PDR. Serum NO levels ranged from 80 to 188 micromol/l, with the highest values obtained in patients with PDR. Taken together, the mean serum NO, sIL-2R, IL-8 and TNF-alpha levels increased with the stage of DR and the highest levels were found in patients with PDR. The PDR patients had significantly (for each, P < 0.001) higher serum NO (166.8 +/- 3.2 micromol/l), sIL-2R (807.9 +/- 33.3 U/ml), IL-8 (17.9 +/- 0.4 pg/ml) and TNF-alpha (15.0 +/- 0.8 pg/ml) levels compared with NPDR patients (149.5 +/- 2.1, 659.4 +/- 23.4, 12.9 +/- 1.1, 11.5 +/- 0.6, respectively), NDR patients (115.9 +/- 5.8, 373.8 +/- 15.0, 8.3 +/- 1.0, 6.6 +/- 0.9, respectively) and controls (116.6 +/- 2.3, 392.4 +/- 16.6, 7.2 +/- 0.3, 7.3 +/- 0.5, respectively). Serum levels of these parameters for NPDR patients were also significantly (for each, P < 0.01) higher compared with those of NDR patients and controls. On the other hand, serum NO, sIL-2R, IL-8 and TNF-alpha levels of patients with NDR were comparable with those of controls (for each, P > 0.05). CONCLUSION: The results of the present study suggest that NO, sIL-2R, IL-8 and TNF-alpha may play important roles in the pathophysiology and progression of DR. We think that these potentially inflammatory cytokines and NO with their endothelial implications may act together during the course and progression of DR. These molecules may serve as therapeutic targets for the treatment and/or prevention of diabetes with its systemic and ocular microvascular complications.     

Decreased nitric oxide production in primary open-angle glaucoma

PURPOSE: Raised intraocular pressure (IOP) is the major risk factor responsible for optic nerve damage in primary open-angle glaucoma (POAG). The trabecularmeshwork acts as a valve in aqueous outflow and relaxes with nitric oxide (NO) agonists. Since NO is synthesized by endothelium and smooth muscle elsewhere in the body, this study investigated the NO levels in the aqueous humor of patients with POAG compared with cataract patients. MATERIALS AND METHODS: Aqueous humor samples were taken by paracentesis from 16 consecutive patients with POAG (9 male and 7 female; mean age 69.0+/-3.4 yrs) and 14 age and sex-matched controls with cataract (8 male and 6 female; mean age 66.7+/-4.1 yrs) during elective surgery. As an indicator for NO, aqueous total nitrite levels (end - product of NO) were measured by Greiss reaction. The Mann-Whitney U test was used for statistical analysis and P <0.05 was considered significant. RESULTS: The mean age and sex in two groups were comparable. The mean aqueous humor NO levels were significantly (P = 0.001) lower in patients with glaucoma (72.72+/-11.21 micromol/L) than in patients with cataract and no glaucoma (86.92+/-11.23 micromol/L). CONCLUSIONS: Decreased NO production in patients with POAG indicates that NO-producing cells may be lost as the disease progresses. The control of NO levels in the eye might be a therapeutic target in glaucoma.     

Serum acetylcholinesterase and prognosis of acute organophosphate poisoning

OBJECTIVE: The aim of this study is to investigate the prognostic value of serum acetylcholinesterase levels and their relationship with neurological syndromes (Type 1 syndrome, intermediate syndrome, and delayed polyneuropathy) in acute organophosphate poisoning. MATERIALS AND METHODS: Thirty-two consecutive patients with acute organophosphate poisoning admitted to the Ondokuz Mayis University Emergency Department from June 1999 to January 2001 were evaluated. Patients were assessed according to admission time, symptoms, and results of clinical exams and their serum acetylcholinesterase levels were determined on days 1, 2, 3, 7, and the last day. RESULTS: There was no significant difference between the first-day serum acetylcholinesterase of the patients with severe poisoning (n = 22, 68.75%) and of the patients with mild poisoning (n = 10, 31.25%; NS). There was no discernible difference between the serum acetylcholinesterase obtained on days 1 and 3 after poisoning from the patients with intermediate syndrome (n = 5, 15.6%; means: 0.90 +/- 0.65 vs. 0.88 +/- 0.53, 19.35 vs. 18.92%; NS, sensitivity = 80%; specificity = 87.5%). There was a significant difference between the serum acetylcholinesterase obtained on days 1 and 3 from the patients with nonintermediate syndrome (n = 24, 75%; means: 1.05 +/- 0.24 vs. 1.68 +/- 0.29, 22.58 vs. 36.12%; p < 0.001). There was no discernible significant difference in serum acetylcholinesterase between the patients with organophosphorus-induced delayed polyneuropathy (n = 7, 21.8%) and nonorganophosphorus-induced delayed polyneuropathy. In the patients who died (n = 5, 15.6%), serum acetylcholinesterase showed no discernible increase day 1-the last day (means: 0.50 +/- 0.25 vs. 0.46 +/- 0.26, 10.75 vs. 9.89%; NS). There was a significant difference between the serum acetylcholinesterase levels obtained on days 1 and the last day from the patients who survived (n = 27, 84.3%; means: 1.14 +/- 0.25 vs. 2.32 +/- 0.26, 24.51 vs. 49.89%; p < 0.001). CONCLUSION: In the acute phase of organophosphate poisoning, low serum acetylcholinesterase (> 50% of minimum normal value) supports the diagnosis of organophosphate poisoning but it does not show a significant relationship to the severity of poisoning (NS). The serum acetylcholinesterase activity may be a useful parameter in following the acute prognosis of organophosphate poisoning.     

Basic toxicological approach has been effective in two poisoned patients with amitraz ingestion: case reports

Amitraz, a formamidine insecticide and acaricide used in veterinary practice, presents side effects in humans related to its pharmacological activity on alpha 2-adrenergic receptors. There is little information available in the literature about the toxicology of the product in man and the treatment of this poisoning. In this report, the clinical and laboratory features of amitraz poisoning in two patients by a veterinary formulation also containing xylene are presented. The major clinical findings were unconsciousness, drowsiness, respiratory failure requiring mechanical ventilation, miosis, hypothermia and bradycardia. The laboratory findings were hyperglycemia, hypertransaminasemia and increased urinary output. Supportive management of this poisoning in humans is suggested in only a few articles and there is no specific antidote for the subsequent possible pharmacological effects of amitraz. In our two cases, we performed supportive treatment such as mechanical ventilation, atropine, gastric lavage, active carbon, oxygen and fluid administration. We concluded that the basic approach to the patient with amitraz poisoning, including initial stabilization to correct immediate life-threatening problems, treatment to reduce absorption and measures to improve elimination of the toxin, is effective.     

Effect of 5-lipoxygenase inhibition on Kupffer cell clearance capacity in obstructive jaundiced rats

BACKGROUND: Obstructive jaundice is a common surgical problem. It may cause hepatic and Kupffer cell dysfunction. Previous studies demonstrated that 5-lipoxygenase inhibition prevents hepatic injury. However, its effect on Kupffer cell clearance capacity has not been determined yet. MATERIALS AND METHODS: Rats were divided into four groups. In group 1 (sham control group), only bile duct dissection was performed. In other groups bile ducts were ligated and divided. In groups 1 and 2 saline, in group 3 ethanol, and in group 4 a 5-lipoxygenase inhibitor AA-861 was given intraperitoneally to the animals. Rats were sacrificed 14 days after the operations. Serum alkaline phosphatase, total bilirubin, and alanine aminotransferase levels were determined. Kupffer cell clearance capacity was measured using an in situ isolated hepatic perfusion technique. Hematoxylin-eosin-stained liver samples were evaluated under light microscope for histopathologic scoring. RESULTS: Rats in the sham control group had significantly lower serum ALP and bilirubin values than those in the experimental groups with biliary obstruction. AA-861 administration significantly decreased serum ALT levels and histopathologic scores. There was no significant difference in ALT levels and histopathologic scores between the sham control and AA-861 groups. Kupffer cell clearance capacity was found to be significantly increased in the AA-861 group compared to other experimental groups with obstructive jaundice. CONCLUSIONS: This study shows that leukotriene synthesis inhibition using AA-861 prevents hepatic damage and improves Kupffer cell clearance capacity in obstructive jaundiced rats. This may have significant implications for the management of patients with obstructive jaundice.     

Retrospective comparison of surgical techniques to prevent secondary opacification in pediatric cataracts

PURPOSE: To evaluate the effect of different surgical methods for management of the posterior capsule and anterior vitreous on the rate of posterior capsule opacification in pediatric cataracts. METHODS: Charts of 34 children (47 eyes) aged 40 days to 18 years (mean: 8.5 years) who had primary cataract surgery with or without posterior chamber intraocular lens (IOL) implantation during the past 5 years were reviewed. In 26 eyes, cataracts were managed with a posterior continuous curvilinear capsulorhexis, and in 21 eyes, the posterior capsule was left intact. Follow-up averaged 10 months (range: 6.5 months to 5 years). RESULTS: Visually significant secondary cataract developed in nine eyes with intact posterior capsules, and seven eyes required Nd:YAG laser posterior capsulotomy. The average time for YAG capsulotomy postcataract removal in the second group was 4 months. The visual axis remained clear in all eyes that had posterior continuous curvilinear capsulorhexis with or without posterior chamber IOL. Complications such as fibrinoid membrane, stromal edema, posterior synechiae, updrawn pupil, and transient glaucoma occurred in both groups at a similar rate. CONCLUSION: Primary posterior continuous curvilinear capsulorhexis is an effective method for preventing secondary cataract formation in pediatric cataracts.     

Low Dose Ketoconazole is an Effective and a Relatively Safe Alternative in the Treatment of Hirsutism*

Summary: Efficacy, clinical and hormonal effect of ketoconazole in 400 mg/day dose was tested in a prospectively-designed study. Twenty four patients with hirsutism according to the Ferriman and Gallwey score (>8) and elevated blood androgen levels were administered 400 mg/day ketoconazole for 6 months. Basal and posttherapy early follicular phase androgens and biochemical parameters were evaluated. In 22 patients significant improvement and in 2 slight improvement was seen in subjective complaints. No side-effects were observed in these patients other than 2 cases of pruritus (transient), 2 mild gastric upset and 1 mastodynia. All patients completed the study. Low dose ketoconazole seems to be effective in the treatment of hirsutism with relatively few side-effects but still should be reserved as an alternative choice due to the potential for deleterious hepatic effects.