Array-CGH and clinical findings in a patient with a small supernumerary r(8) mosaicism.

Small supernumerary ring chromosomes (sSRC) represent a subset of small supernumerary marker chromosomes (sSMC) where r(8) is relatively common. The phenotype sSRC(8) ranges from almost normal to variable degrees of abnormalities in mosaic or non-mosaic conditions. We present a new patient of de novo mosaic supernumerary ring chromosome 8 which has trisomy of a region of chromosome 8p11.21-q21.13. Mosaicism for a ring chromosome was showed by routine karyotyping that revealed a karyotype of mos47,XY,+r(?) [47]/46,XY [36] and we performed array comparative genomic hybridization (array-CGH) in order to precisely define the extension about chromosomal origin of the duplicated region in a patient. Array-CGH analysis confirmed that the sSRC derived a 43.921 Mb genomic gain of chromosome 8 (p11.21-q21.13). Common clinical features of the patient included multiple congenital anomalies, developmental delay, thoracolumbar scoliosis, mild pulmonary stenosis, laryngomalacia, hypospadias and atypical facial appearance. With this study a patient involving mosaic trisomy 8p11.21-q21.13 along with clinical properties, is described and compared to previously reported cases involving partial trisomy 8q.

Could red cell distribution width be a marker in Hashimoto's thyroiditis?

AIMS: Hashimoto's Thyroiditis (HT) is the most common autoimmune thyroiditis worldwide and characterized with lymphomonocytic inflammation of the thyroid gland. Red cell distribution width (RDW) reflects erythrocyte anisocytosis and besides it increases in iron deficiency anemia, recent studies reported that RDW was also associated with conditions characterized with overt or subclinical inflammation. We aimed to answer whether RDW increased in Hashimoto's thyroiditis. METHODS: Patients with HT admitted to outpatient clinic of our hospital were included to the study. Patients with anemia (especially iron deficiency), diabetes mellitus, chronic inflammatory disease and on medication that may affect hemogram results (e. g., aspirin) excluded from the study. Patient characteristics, thyroid stimulating hormone (TSH), Free T3 (FT3), Free T4 (FT4), Anti-thyroid peroxidase (Anti-TPO), Anti-Thyroglobulin (Anti-TG), leukocyte count (WBC), Hemoglobin (Hb), Hematocrit (Htc), mean corpuscular volume (MCV), RDW and platelet count (PLT) values of the study cohort were obtained from computerized database of our institution. RESULTS: There was no significant difference between study and control groups in terms of WBC, Hb, Htc, MCV, PLT, PDW and FT3 levels. However, FT4 level was significantly lower and TSH was significantly higher in study group compared to controls. RDW was significantly increased in study group compared to control group. CONCLUSION: We suggest that elevated RDW values in patients without iron deficiency anemia may require further evaluation for HT, especially in female population.

Treatment of iron deficiency anemia induces weight loss and improves metabolic parameters.

BACKGROUND: The treatment of iron deficiency anemia is oral iron replacement which has side effects mostly related with gastrointestinal system. A significant rate of the patients that discontinuing the treatment complained of weight gain during treatment in our clinical practise, despite, oral iron preparations are not known to have such a side effect in adults. Therefore, we planned to investigate this myth whether iron preparations cause an increase in weight, waist circumference, body mass index and laboratory metabolic parameters that may accompany to weight gain. MATERIALS AND METHODS: Twenty-one women admitted to our out-patient clinics with iron deficiency anemia were enrolled to the study. Waist circumference, body weight, body mass index, systolic and diastolic blood pressures, hemogram and other laboratory parameters assessed and recorded at the first visit and repeated 4 to 6 moths after initiation of treatment. RESULTS: Waist circumference, body weight and BMI significantly reduced in patients after treatment compared to pre-treatment period. Moreover, HDL was increased and triglyceride was decreased significantly in after treatment compared to pre-treatment period. CONCLUSIONS: We suggest that treatment of iron deficiency may improve not only haematological but also metabolic and anthropometric parameters. Due to the small study population of our cohort, larger prospective studies are needed to confirm our results.

Serum amyloid A and Omentin levels in acute appendicitis: a preliminary study for a novel diagnostic approach.

BACKGROUND: The diagnosis of acute appendicitis is based on medical history and physical examination. Serum (S) amiloid A (AA) levels are elevated in many inflammatory conditions. Omentin is a recently discovered adipokine showing decreased levels associated with inflammatory conditions. We aimed to measure SAA and omentin levels in patients with acute appendicitis. MATERIALS AND METHODS: 36 patients with a diagnosis of acute appendicitis and 30 healthy subjects were enrolled to this research study. A statistical analysis was performed using IBM SPSS Statistics Version 16.0 (SPSS Inc.®, Chicago, IL, United States). RESULTS: Patients in study group were significantly older than healthy control subjects (p=0.013). Body mass index of the patients with acute appendicitis (23.2 ± 1.3) was greater than that of the control group (22.7 ± 1), but the difference did not reach the statistically significance (p=0.076). ). Mean level of SAA was significantly raised in study group compared to healthy control subjects (p< 0.001). Mean omentin level was significantly lower in study group compared to healthy subjects (p=0.013). CONCLUSIONS: In conclusion, although diagnosis of acute appendicitis is mostly based on clinical findings, omentin and especially SAA measurement in serum may help surgeons to avoid negative laparatomy.

Association between omentin levels and insulin resistance in pregnancy.

AIMS: Omentin is a new adipokine secreted mainly from visceral adipose tissue. Serum omentin is found to be reduced in patients with impaired glucose tolerance, type 2 diabetes mellitus, obesity and insulin resistant states. Despite the fact that pregnancy is also characterized with hyperinsulinemia, literature is lacking about data of omentin levels and its association with insulin resistance in pregnant women. We aimed to evaluate the association of omentin levels and insulin resistance in pregnant women and to compare these levels with those of non-pregnant, non-diabetic women. METHODS: Uncomplicated pregnant women who admit to our outpatient clinics for routine follow-up were included in the study group. Non-pregnant women without diabetes mellitus were served as control group. Fasting glucose, insulin, omentin levels and HOMA IR were recorded. SPSS 15.0 for Windows was used for statistical analysis. RESULTS: There were 36 pregnant women in the study group and 37 healthy, non-pregnant women in the control group. Serum omentin and fasting glucose levels were significantly decreased and fasting insulin was significantly increased in the study group compared to control group. CONCLUSION: Omentin might be an indicator of insulin resistance in pregnant women. Larger prospective studies are needed to claim whether omentin can have a clinical use for diagnosis of gestational diabetes mellitus.

Platelet function in euthyroid patients undergoing thyroidectomy in women.

BACKGROUND: Several studies have reported several platelet abnormalities in patients with sub-clinical or overt thyroid dysfunctions. The primary mechanism that affects the hemostatic balance is excess or deficiency of thyroid hormones. The different ways of thyroid gland to the platelet function are not yet clearly understood. The relationship between in the thyroid gland and platelet activation without thyroid hormones has not been studied yet. AIM: The aim of our study is to determine the platelet function in euthyroid patients undergoing thyroidectomy in females. PATIENTS AND METHODS: The study group includes 52 female euthyroid patients undergoing thyroidectomy. The control group consisted with 21 healthy euthyroid female. Platelet count (PC), platelet mass (PM), mean platelet volume (MPV), and platelet distribution width (PDW) were measured. PM was calculated by multiplying MPV and PLT. RESULTS: MPV (8.4 ± 1.3 versus 7.9 ± 0.8) and PDW (17.8 ± 1 versus 17.6 ± 0.8) values were similar between the two groups. CONCLUSIONS: Thyroid gland does not directly affect platelet activation. Accordingly, platelet abnormalities of thyroid disease can be considered to be independent of the underlying thyroid tissue. This finding suggests that association between thyroid diseases and platelet function is dependent on the status of thyroid hormones.

Mean platelet volume in nasal polyps / Volumen medio de las plaquetas en los pólipos nasales

BACKGROUND: Many studies in literature point out that inflammation related to nasal polyp is mostly dependent on eosinophils and their inflammatory products. Beside eosinophils, platelets may have a role in nasal polyp development. Platelets are involved in haemostasis, tissue repairing and inflammation. However, to our knowledge, there are no reports in the literature that study the association between platelet parameters and nasal polyps. SUBJECTS AND METHODS: Forty-three patients with nasal polyps and forty-nine healthy controls were enrolled in the study, retrospectively. Laboratory data ofpatients with nasal polyp were obtained at the time of diagnosis. RESULTS: There were no statistically significant differences between the two groups in terms of white blood count, haemoglobin, haematocrit and platelet count. The mean platelet volume (MPV) value of the nasal polyp group was significantly lower than the control group (p = 0.025). Mean eosinophil count was significantly elevated in the nasal polyp group compared to the control group (p < 0.001). CONCLUSIONS: Reduction in MPV may be an indicator for nasal polyp formation. Further studies with a larger study population are needed to detect the possible correlation between eosinophil count and MPVvalues in patients with nasal polyps.

ANTECEDENTES: Muchos estudios en literatura señalan que las inflamaciones relacionadas con los pólipos nasales dependen en su mayoría de los eosinófilos y sus productos inflamatorios. Además de los eosinófilos, las plaquetas pueden jugar un papel en el desarrollo de los pólipos nasales. Las plaquetas participan en la hemostasia, la reparación de tejidos, y la inflamación. Sin embargo, que sepamos, la literatura existente no reporta estudios acerca de la asociación entre los parámetros de las plaquetas y los pólipos nasales. SUJETOS Y MÉTODOS: Cuarenta y tres pacientes con pólipos nasales y cuarenta y nueve controles sanos se inscribieron en el estudio, de forma retrospectiva. Se obtuvieron datos de laboratorio de los pacientes con pólipos nasales en el momento del diagnóstico. RESULTADOS: No se encontraron diferencias estadísticamente significativas entre los dos grupos en términos de glóbulos blancos, hemoglobina, hematocritos y conteo de plaquetas. El valor medio de las plaquetas (MPV) del grupo con pólipos nasales fue significativamente menor que el del grupo control (p = 0. 025). El conteo medio de eosinófilos fue significativamente elevado en el grupo con pólipos nasales en comparación con el grupo control (p < 0.001). CONCLUSIONES: La reducción de MPVpuede ser un indicador para la formación de pólipos nasales. Se necesitan estudios adicionales con una mayor población de estudio para detectar la posible correlación entre los valores de MPV y el conteo de eosinófilos en pacientes con pólipos nasales.

Mean platelet volume in nasal polyps.

BACKGROUND: Many studies in literature point out that inflammation related to nasal polyp is mostly dependent on eosinophils and their inflammatory products. Beside eosinophils, platelets may have a role in nasal polyp development. Platelets are involved in haemostasis, tissue repairing and inflammation. However, to our knowledge, there are no reports in the literature that study the association between platelet parameters and nasal polyps. SUBJECTS AND METHODS: Forty-three patients with nasal polyps and forty-nine healthy controls were enrolled in the study, retrospectively. Laboratory data of patients with nasal polyp were obtained at the time of diagnosis. RESULTS: There were no statistically significant differences between the two groups in terms of white blood count, haemoglobin, haematocrit and platelet count. The mean platelet volume (MPV) value of the nasal polyp group was significantly lower than the control group (p = 0.025). Mean eosinophil count was significantly elevated in the nasal polyp group compared to the control group (p < 0.001). CONCLUSIONS: Reduction in MPV may be an indicator for nasal polyp formation. Further studies with a larger study population are needed to detect the possible correlation between eosinophil count and MPV values in patients with nasal polyps.

Gene expression profiling of B-CLL in Ukrainian patients in post-Chernobyl period.

BACKGROUND: Genetic mechanisms that result in the development and progression of B-cell chronic lymphocytic leukemia (B-CLL) are mainly unknown. We have analyzed gene expression patterns in Ukrainian B-CLL patients with the aim of identifying B-CLL involved / associated genes in order to shed light on the biology of this pathological entity. MATERIAL AND METHODS: The samples of the peripheral blood and bone marrow of 44 Ukrainian B-CLL patients with no characteristics indicative of unfavorable course of the disease such as CD38 were analyzed morphologically and immunocytochemically according to the new WHO classification. Total RNA was isolated, and gene expression levels were determined by microarray method comparing with the sample from 17 healthy donors. RESULTS: We investigated interactions using the Ingenuity Pathway Analysis (IPA) software and found 1191 network eligible up-regulated genes and 3398 Functions/Pathways eligible up-regulated genes, 1225 network eligible down-regulated genes and 2657 Functions/Pathways eligible down-regulated genes. CONCLUSION: In B-CLL patients, gene networks around MYC, HNF1A and HNF4A, YWHAG, NF-κB1 and SP1 are identified as up-regulated; CEBPA, YWHAG, SATB1 and RB1 -- as down-regulated. G protein coupled receptor signaling, arachidonic acid and linoleic acid metabolisms, calcium signaling, metabolism of xenobiotics by cytochrome P450 are found out as significant up-regulated pathways. EIF2 and Cdc42 signaling, regulation of eIF4 and p70S6k signaling, protein ubiquitination pathway and oxidative phosphorylation are the most significant down-regulated pathways obtained in our study. The involvement of NF-κB gene network and upregulated levels of G protein coupled receptor signaling pathway, which has an important role in transcription of NF-κB, are important and need further examination.

Microarray-based gene expression analysis of an animal model for closed head injury.

OBJECTIVE: Traumatic brain injury (TBI) is a major cause of death and disability in both children and the elderly. Mortality from TBI is said account for 1-2% of all deaths. One-third to one-half of all traumatic deaths is due to head injury. Of those who survive, the majority is left with significant disabilities, including 3% who remain in a vegetative state and only approximately 30% who make a good recovery. Microarray studies and other genomic techniques facilitate the discovery of new targets for the treatment of diseases, which aids in drug development, immunotherapeutics and gene therapy. Gene expression profiling or microarray analysis enables the measurement of thousands of genes in a single RNA sample. METHODS: In this study, adult Wistar-albino rats underwent TBI using a trauma device. Brain tissues and blood samples were taken for gene expression at 1, 12 and 48 h post-trauma and were then analysed via microarray. Total RNA was isolated using an RNeasy Mini Kit (QIAGEN-Sample & Assay Technologies, Hilden, Germany) and tested using a 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA). Overall changes in gene expression were evaluated using Agilent Whole Rat Genome 4 × 44 K oligonucleotide arrays and analysed with GeneSpring (GeneSpring 6.1, Silicon Genetics, Redwood City, CA) software. Only genes with a signal-to-noise ratio of above 2 in the experiments were included in the statistical analysis. RESULTS: ANOVA (p<0.05) was performed to identify differentially expressed probe sets. Additional filtering (minimum 2-fold change) was applied to extract the most differentially expressed genes based on the study groups (Control vs. 1st hour, Control vs. 12th hour, Control vs. 48th hour). Differentially expressed genes were detected via microarray analysis. A gene interaction-based network investigation of the genes that were identified via traditional microarray data analysis describes a significantly relevant gene network that includes the C1ql2, Cbnl, Sdc1, Bdnf, MMP9, and Cd47 genes, which were differentially expressed compared with the controls. CONCLUSIONS: In this study, we will review the current understanding of the genetic susceptibility of TBI with microarrays. Our results highlight the importance of genes that control the response of the brain to injury as well as the suitability of microarrays for identifying specific targets for further study.

Quantitative real time PCR analysis of apoptosis-related gene expression in leukemias in Ukrainian patients.

BACKGROUND: The complete medical consequences of the long-term exposure of population to ionizing radiation in post-Chernobyl period are still a controversial issue. The molecular biological analysis of malignant diseases of hematopoietic and lymphoid tissues in contaminated territories requires the precise diagnosis based on criteria of novel classifications. AIM: To analyze the relative gene expression of six apoptosis-related genes in different types of tumors of hematopoietic and lymphoid tissues in patients living in areas of Ukraine contaminated with radionuclides in post-Chernobyl period. MATERIAL AND METHODS: The samples of the peripheral blood and bone marrow of 189 Ukrainian leukemia patients and 16 patients with reactive lymphocytosis were analyzed morphologically and immunocytochemically for precise delineation of the main forms and cytological variants of hematological malignancies according to new WHO classification. Expression of six apoptosis-related genes was analyzed in the individual samples of 9 different groups of malignant diseases of hematopoietic and lymphoid tissues and one group of patients with reactive lymphocytosis by quantitative RT-PCR. Expression of genes was assessed relative to that in control group of healthy donors. RESULTS: Up-regulation of six analyzed apoptosisrelated genes is observed in all groups of leukemia. In most groups of leukemia being analyzed, BCL-2 up-regulation level is superior to that of BAX. Prominent MYC up-regulation is observed in B-lymphoblastic leukemia/lymphoma, non-Hodgkin's lymphoma, and T-lymphoblastic leukemia/lymphoma groups. In myelodysplastic/myeloproliferative neoplasms, the striking up-regulation of Fas-1 and P38MAPK is evident. Practically all the groups of leukemia are characterized by stable high ratios of P53 up-regulation. CONCLUSION: In Ukrainian patients, up-regulation of six analyzed apoptosis-related genes is observed practically in all types of malignant diseases of hematopoietic and lymphoid tissues under study. Microarray-based analysis of these samples would be of great importance in terms of elucidating genomic interactions in leukemias and their possible association with ionizing radiation.

Differential expression of 16 genes coding for cell cycle- and apoptosis-related proteins in vitamin D-induced differentiation of HL-60 cells.

OBJECTIVE: The aim of the study was to analyze expression of several genes related to cell cycle regulation and apoptosis in realization of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced differentiation of HL-60 cells. METHODS: The cultured HL-60 cells were treated with 1,25(OH)2D3. Quantitative real-time PCR was used for analyzing the changes in expression of 16 genes (Bcl-2, Bcl-xL, Mcl-1, Bik, caspase 6, caspase 7, cytochrome c, TNFR1, Myc, TGF-beta, JNK1, p38MAPK, p21, p27, Cdk2, cyclin E) at early phases of cell differentiation of HL-60 cells induced by 1,25(OH)2D3. RESULTS: Among investigated genes, Bik and Myc gene expression was down-regulated at 48 h time points. JNK1 gene was markedly up-regulated and caspase-6 and cyclin E genes were down-regulated at 18 h time point. CONCLUSION: These findings suggest that there are no distinct apoptotic signals at early phases of cell differentiation. It is speculated that changes in the expression of the genes involved in vitamin D-induced apoptosis of HL-60 cells could be better visualized after the terminal stages of cell differentiation.

The evaluation of the Turkish version of the Well-being Questionnaire (WBQ-22) in patients with Type 2 diabetes: the effects of diabetic complications.

OBJECTIVE: Psychopathological conditions including depression and anxiety are important in patients with diabetes due to their negative effects on the quality of life, treatment and glycemic control. The specially designed questionnaire for diabetics, the Well-being Questionnaire (WBQ-22), was used to determine the psychological well-being in Turkish diabetic patients. METHOD: A total of 100 patients, 45 males and 55 females, were included in the study. Patients completed WBQ-22 questionnaire. RESULTS: Sex, in-patient follow-up, age, duration of diabetes, form of treatment, diabetic microvascular complications, diabetic foot, and increased number of complications were the factors detected to have an effect on the scores of general well-being or its subscales. Scores of depression and general well-being were 7.10 +/- 3.82 and 39.74 +/- 12.27 in females, and 4.20 +/- 3.48 and 48.84 +/- 11.45 in males (p<0.05). Anxiety score was found to be 5.70 +/- 3.71 in the outpatient clinic, and 7.28 +/- 4.38 in the inpatient clinics (p<0.05). General well-being score was 49.40 +/- 8.83 in patients having a diabetes duration of 1 yr or less and 33.70 +/- 8.83 in patients with 20 yr or more (p<0.05). Patients treated with insulin had depression score of 7.02 +/- 4.07 whereas patients treated with diet had 4.50 +/- 3.27 (p<0.05). The increasing total chronic complication points were also found to have a negative effect on WBQ-22 scores. General well-being score was 51.08 +/- 9.84 in patients with no complications and 34.50 +/- 14.14 in patients with 4 complications (p<0.05). CONCLUSIONS: Psychosocial support should be provided to Type 2 diabetic patients by studying the psychological well-being with WBQ-22 questionnaire.

Resistance emergence among P. aenrginosa in a rat thigh-abscess model. Comparison of imipenem and meropenem treatment.

Resistance emergence to carbapenem antibiotics was studied in a rat-thigh abscess model. Abscesses were developed in three groups with a total of 15 P. aeruginosa strains (three rats per strain). Groups were assigned to imipenem or meropenem treatment while one was left antibiotic-free. Test strains were fully susceptible to these antibiotics and the "Mutant Preventing Concentrations" of imipenem and meropenem over these strains were comparable. Antibiotic serum levels, assessed by serum bioassay test, were similar among therats. After four days, rats (n=45) were sacrificed and carbapenem resistant mutants were selected on imipenem (4 mg/L) and meropenem (4 mg/L) supplemented agar plates. Resistant variants of three strains, from four abscesses, were detected; one in the meropenem group, two in the imipenem and one in the untreated group. The MICs of imipenem and meropenem for the mutants were increased fourfold times or even higher of their counterparts. Resistance emergence under antibiotic pressure in P. aeruginosa has been shown in various conditions. To our knowledge, however, resistance emergence in abscess and also the comparison of imipenem and meropenem in this regard has not been studied before.

Plasma lipid peroxidation products and antioxidant enzyme activities in patients with type 2 diabetes mellitus.

Diabetes is associated with a significant increase in thiobarbituric acid reactive substances (TBARS) which are considered as an index of endogenous lipid peroxidation. The human body has a complex antioxidant defense system that prevents the initiation of free radical chain reactions. We measured plasma TBARS levels, superoxide dismutase (SOD) and catalase (CAT) activities and compared their relation to the metabolic control of diabetes and diabetic microangiopathy. Sixty-four patients (19 men), aged 52.35+/-9.31 years with type 2 diabetes mellitus were included in the study. Thirty-six healthy subjects (12 men), aged 51.02+/-7.01 years formed the control group. TBARS levels and SOD activity were elevated in the diabetic group when compared with the control group ( p<0.001 and p<0.00001, respectively). However CAT activity was significantly decreased in the diabetic group when compared with the control group ( p<0.00001). Patients with diabetic nephropathy and retinopathy, but not neuropathy, had elevated TBARS levels but there was no statistically significant difference when compared with diabetic patients without microangiopathy ( p>0.05). There was a positive correlation between plasma TBARS levels and SOD activity (r=0.770, p=0.0001) and a negative correlation between plasma TBARS levels and CAT activity (r=0.482, p=0.0001). There was also a negative correlation between SOD and CAT activities (r=-0.609, p=0.0001). We found significantly elevated TBARS levels in diabetic patients. We did not observe any correlation between TBARS levels and blood glucose and HbA(1c) levels. Elevated TBARS levels and SOD activity and decreased CAT activity may be due to a compensation mechanism of the body.

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.

The relation between plasma endothelin-1 levels and metabolic control, risk factors, treatment modalities, and diabetic microangiopathy in patients with Type 2 diabetes mellitus.

We evaluated the possible relation between plasma endothelin-1 (ET-1) levels and metabolic control, risk factors, treatment modalities, and diabetic microangiopathy, including nephropathy, neuropathy, and retinopathy in patients with Type 2 diabetes and healthy control group. Sixty-eight (39 females and 29 males) patients with Type 2 diabetes and 14 (6 females and 8 males) healthy subjects were included in the study. Plasma ET-1 levels were found to be 10.46+/-1.24 pmol/l in the diabetic group, whereas 7.97+/-0.41 pmol/l in the control group, which was statistically significant (P<.01). We also found elevated plasma ET-1 levels in patients with the least one microvascular complication when compared with the uncomplicated diabetes group (P=.02). Moreover, plasma ET-1 levels of the uncomplicated group was higher than the control group (P<.05). Plasma ET-1 levels were significantly elevated in hypertensive diabetics than normotensive diabetics (t=2.58, P=.012). It was also found to be elevated in diabetic patients with diabetes duration of more than 10 years when compared with patients less than 10 years (P=.02). These findings can be interpreted as the increased damage of microvascular complications in the disease process that may lead to elevated ET-1 levels. Mean plasma ET-1 levels in diabetic patients with a family history of diabetes was found to be higher than patients with no family history of diabetes. Genetical and environmental factors may have an effect on ET-1 level. We also studied the correlations of plasma ET-1 levels on age, sex, fasting blood glucose levels, treatment modalities HbA1c, hyperlipidemia, C-peptide, Body Mass Index, and smoking, but did not find any statistically significant difference. In conclusion, plasma ET-1 levels are well correlated with microangiopathy, hypertension, increased disease duration, and family history of diabetes, but poorly correlated with metabolic control, treatment modalities, age, sex, hyperlipidemia, obesity, and smoking.

Occult parathyroid carcinoma in a patient with papillary thyroid carcinoma and Hashimoto's thyroiditis.

A 47-year-old female patient with a previous history of right thyroid lobectomy was admitted to the hospital because of a 3 cm nodule in the thyroid gland. Hormonal evaluation showed subclinical hypothyroidism with serum levels of thyroid stimulating hormone slightly elevated to 4.4 microg/dl (normal: 0.4-4 microg/dl). Thyroid ultrasound showed diffuse irregularity of the gland and the presence of a solitary nodule (30x18 mm in diameter) localized in the left lobe. A fine needle aspiration biopsy was performed. Cytological analysis revealed papillary thyroid carcinoma and Hashimoto's thyroiditis. Total thyroidectomy was performed. During the operation, two of the parathyroid glands were detected to be hyperplastic. Histopathological examination of the thyroid and parathyroid glands revealed Hashimoto's thyroiditis with papillary thyroid carcinoma and synchronous carcinoma of the parathyroid gland. To our knowledge, this association of occult parathyroid carcinoma in a patient with papillary thyroid carcinoma and Hashimoto's thyroiditis has not been reported in the literature. Given the high prevalence of autoimmune diseases in elderly women, a random occurrence of this triad represents the most likely explanation.

Paroxysmal Nocturnal Haemoglobinuria in the Differential Diagnosis of Unresponsive Iron Deficiency Anemia: A Case Report.

A 16-year-old male patient who was on oral iron treatment for iron deficiency anemia for the last one year was seen at the Haematology clinic with complaints of weakness, pallor, and jaundice. A complete blood count revealed Hb of 4.2 mmol/L, Hct of 0.14, and MCV of 76 fl. A blood smear showed 50% neutrophils, 40% lymphocytes, and 10% monocytes with anisocytosis, poikilocytosis, polichromasia in erythrocytes and normoblasts. Reticulocyte count was under 1%. There was a slight erythroid hyperplasia in the bone marrow aspiration. Biochemical examinations showed total bilirubin of 3.9 mg/dL, indirect bilirubin of 3.4 mg/dL, and lactate dehydrogenase (LDH) of 6085 U/L (220-450). In re-evaluating the history of the patient, he was seen to be complaining of dark discoloration of morning urine. Perl's reaction was found to be positive for hemosiderin in the urine sediment. Because Ham's test was positive, the levels of CD55, 58, and 59 proteins on erythrocyte membranes were found to be lower. The patient was started 32 mg of methylprednisolone and his anaemia was improved by the 14th day of treatment. When evaluating iron deficiency anemia resistant to iron supplementation, PNH should be kept in mind.