Investigation of IL-35 and IL-39, New Members of the IL-12 Family, in Different Clinical Presentations of Brucellosis.

Brucellosis is significantly influenced by the interactions between the causative Brucella bacteria and host immunity. Recently identified cytokines have been described for their immunomodulatory effects in numerous inflammatory, autoimmune and infectious diseases. Some of them are new members of cytokine superfamilies, including several members of the IL-12 superfamily (IL-35, IL-39). The major purpose of the present study was to investigate the role of these new immunomodulatory cytokines in Brucella infections. The levels of IL-35 and IL-39 in the serum of 40 acute and 40 chronic brucellosis patients and 40 healthy controls were measured by ELISA. The mRNA levels of IL-35 and IL-39 in PBMCs were detected by RT-qPCR. Both IL-35 and IL-39 serum concentrations were significantly higher in healthy control subjects than in brucellosis patients, and IL-35 and IL-39 serum levels of chronic brucellosis patients were higher than those of acute cases. It was also found that the expression of Ebi3/IL-12A (IL-35 genes) and Ebi3/IL-23A (IL-39 genes) was upregulated in chronic brucellosis patients compared to healthy controls. Moreover, the expression of the Ebi3/IL-12A and Ebi3/IL-23A genes was lower in patients with acute brucellosis than in patients with chronic brucellosis. Overall, this study showed that IL-35 and IL-39 are positively correlated in brucellosis and significantly decreased during the disease. Significantly lower levels of IL-35 and IL-39 in acute brucellosis than in chronic brucellosis and healthy controls suggest that these cytokines may play a key role in suppressing the immune response to brucellosis and its progression to chronicity.

IL-35 and IL-39, new members of the IL-12 cytokine family, are immunomodulatory cytokines characterized as anti-inflammatory and pro-inflammatory, respectively.In acute and chronic brucellosis, serum IL-35 and IL-39 are significantly decreased.In acute brucellosis, serum IL-35 are significantly lower than in chronic brucellosis, suggesting that this cytokine may play a role in chronification.A positive correlation was found between IL-35 and IL-39 in acute and chronic brucellosis, suggesting that the common protein subunit Ebi may be suppressed.According to the results of this study, IL-35 and IL-39 may play a role in the pathogenesis of brucellosis.

Assessment of CD39 expression in regulatory T-cell subsets by disease severity in adult and juvenile COVID-19 cases.

COVID-19 is a disease characterized by acute respiratory failure and is a major health problem worldwide. Here, we aimed to investigate the role of CD39 expression in Treg cell subsets in COVID-19 immunopathogenesis and its relationship to disease severity. One hundred and ninety COVID-19 patients (juveniles, adults) and 43 volunteers as healthy controls were enrolled in our study. Flow cytometric analysis was performed using a 10-color monoclonal antibody panel from peripheral blood samples. In adult patients, CD39+ Tregs increased with disease severity. In contrast, CD39+ Tregs were decreased in juvenile patients in an age-dependent manner. Overall, our study reveals an interesting profile of CD39-expressing Tregs in adult and juvenile cases of COVID-19. Our results provide a better understanding of the possible role of Tregs in the mechanism of immune response in COVID-19 cases.

PROPROTEIN CONVERTASE 1/3 DEFICIENCY WITH PELVIC EWING SARCOMA.

Proprotein convertase 1/3 (PC 1/3) deficiency is a rare, autosomal recessive disorder caused by mutations in the PCSK1 gene. The disease is characterized by early-onset chronic diarrhea/malabsorption, followed by severe obesity and hormonal deficiencies such as hypocortisolism, hypothyroidism, diabetes insipidus, hypogonadism, growth deficiency, and diabetes mellitus. Ewing's sarcoma is a rare tumor, usually of small dimensions of neuroectodermal origin that is difficult to distinguish pathologically from a primitive neuroectodermal tumor. A 22-year-old female patient with PC 1/3 deficiency was admitted to our clinic with recurrent urinary tract infections. Magnetic resonance imaging (MRI) revealed an 11x12 cm pelvic mass displacing the uterus. A core-needle biopsy was performed on the pelvic mass. As a result of the pathological evaluation, it was diagnosed with pelvic Ewing's sarcoma. The patient was started on the VAC-IE chemotherapy protocol. We report a case of pelvic Ewing's sarcoma in a patient with PC 1/3 deficiency. Further research is needed to assess malignancy risk in metabolic disorders including very rare disorders like PC 1/3 deficiency.

Impact of deforestation on soil carbon stock and its spatial distribution in the Western Black Sea Region of Turkey.

Land use management is one of the most critical factors influencing soil carbon storage and the global carbon cycle. This study evaluates the impact of land use change on the soil carbon stock in the Karasu region of Turkey which in the last two decades has undergone substantial deforestation to expand hazelnut plantations. Analysis of seasonal soil data indicated that the carbon content decreased rapidly with depth for both land uses. Statistical analyses indicated that the difference between the surface carbon stock (defined over 0-5 cm depth) in agricultural and forested areas is statistically significant (Agricultural = 1.74 kg/m(2), Forested = 2.09 kg/m(2), p = 0.014). On the other hand, the average carbon stocks estimated over the 0-1 m depth were 12.36 and 12.12 kg/m(2) in forested and agricultural soils, respectively. The carbon stock (defined over 1 m depth) in the two land uses were not significantly different which is attributed in part to the negative correlation between carbon stock and bulk density (-0.353, p < 0.01). The soil carbon stock over the entire study area was mapped using a conditional kriging approach which jointly uses the collected soil carbon data and satellite-based land use images. Based on the kriging map, the spatially soil carbon stock (0-1 m dept) ranged about 2 kg/m(2) in highly developed areas to more than 23 kg/m(2) in intensively cultivated areas as well as the averaged soil carbon stock (0-1 m depth) was estimated as 10.4 kg/m(2).

Interleukin-2 gene polymorphism in Turkish patients with Behçet's disease and its association with ocular involvement.

Behçet's disease (BD) is a chronic immune-mediated systemic disease, characterized by oral and genital lesions and ocular inflammation. Several cytokine genes may play crucial roles in host susceptibility to BD, because the cytokine production capacity varies among individuals and depends on the cytokine gene polymorphisms. The association of the interleukin (IL)-2 gene polymorphisms with the susceptibility to BD was investigated in this study. DNA samples were obtained from a Turkish population of 97 patients with BD and 76 healthy control subjects. Polymorphisms of IL-2 gene at position -330 and +166 were determined using the polymerase chain reaction with sequence-specific primers. In the patients with BD, there was a significantly increased frequency of IL-2 -330 GT genotype. Interestingly, we demonstrated that the frequencies of IL-2 -330 GT and IL-2 + 166 GG genotypes were increased in BD patients with ocular involvement, whilst IL-2 -330 TT genotype was significantly decreased. Also, analysis of allele frequency demonstrated that the presence of G allele at position +166 of IL-2 seems to be a risk factor for ocular involvement. These results reveal that IL-2 -330 GT genotype may be a susceptibility factor for BD, whereas IL-2 -330 TT genotype seems to display a protective association with BD. Additionally, IL-2 gene polymorphisms might be associated with ocular involvement in BD.

Effects of non-genetic factors on growth traits and survival rate in Karacabey Merino lambs.

This study was conducted with the aim of determining the growth characteristics and survival rate of Karacabey Merino lambs, as well as the non-genetic factors affecting these traits. The study included data from a total of 17659 lambs and 12263 ewes raised in 30 herds between the years 2011 and 2016 as part of the National Sheep and Goat Improvement Project. The average birth weight of the lambs was determined as 3.73±0.05 kg, the average 45th day live weight was 18.43±0.58 kg, the average weaning (average 91.8 days) weight was 31.83±0.24 kg, and the average daily live weight gain until weaning was 289.1±3.91 g. The average survival rate of lambs at weaning was calculated to be 95.67% ± 1.15. The effects of the factors herd, birth year, birth type, birth season and sex were found significant for all traits (p<0.01). It was established that the mortality rate in lambs in large herds was higher during 6 years in which the project was carried out. Due to the high twinning rate in large herds, the number of lambs per worker is increased, and as a result, they cannot be adequately cared for. For this reason, large farms may be encouraged to increase workmanship services in addition to being provided with protective health practices for lambs throughout the birth period. On the other hand, it was determined that the twinning rate was low in small farms. On farms with fewer sheep populations, it may be advised to flush or administer exogenous hormone treatments to ewes in order to increase fertility and help them bear twins.

Interaction of brassinosteroids and polyamines enhances copper stress tolerance in raphanus sativus.

Brassinosteroids (BRs) and polyamines (PAs) regulate various responses to abiotic stress, but their involvement in the regulation of copper (Cu) homeostasis in plants exposed to toxic levels of Cu is poorly understood. This study provides an analysis of the effects of exogenously applied BRs and PAs on radish (Raphanus sativus) plants exposed to toxic concentrations of Cu. The interaction of 24-epibrassinolide (EBR, an active BR) and spermidine (Spd, an active PA) on gene expression and the physiology of radish plants resulted in enhanced tolerance to Cu stress. Results indicated that the combined application of EBR and Spd modulated the expression of genes encoding PA enzymes and genes that impact the metabolism of indole-3-acetic acid (IAA) and abscisic acid (ABA) resulting in enhanced Cu stress tolerance. Altered expression of genes implicated in Cu homeostasis appeared to be the main effect of EBR and Spd leading to Cu stress alleviation in radish. Ion leakage, in vivo imaging of H(2)O(2), comet assay, and improved tolerance of Cu-sensitive yeast strains provided further evidence for the ability of EBR and Spd to improve Cu tolerance significantly. The study indicates that co-application of EBR and Spd is an effective approach for Cu detoxification and the maintenance of Cu homeostasis in plants. Therefore, the use of these compounds in agricultural production systems should be explored.

The Age-Dependent Role of Th22, Tc22, and Tc17 Cells in the Severity of Pneumonia in COVID-19 Immunopathogenesis.

Coronavirus disease 2019 (COVID-19) has clinical manifestations ranging from mild symptoms to respiratory failure, septic shock, and multi-organ failure. Lymphocytes are divided into different subtypes based on their cytokine production pattern. In this study, we investigated the role of cytokine expressions of CD4+ T (T helper [Th]1, Th2, Th17, Th22) and CD8+ T cell subtypes (T cytotoxic [Tc]1, Tc2, Tc17, Tc22) in the pathogenesis of COVID-19. Peripheral blood mononuclear cells (PBMCs) were extracted with Ficoll by density gradient centrifugation from blood samples of 180 COVID-19 patients (children and adults) and 30 healthy controls. PBMCs were stimulated with PMA and Ionomycin and treated with Brefeldin A in the fourth hour, and a 10-colored monoclonal antibody panel was evaluated at the end of the sixth hour using flow cytometry. According to our findings, the numbers of Th22 (CD3+, CD4+, and interleukin [IL]-22+) and Tc22 (CD3+, CD8+, IL-22+) cells increased in adult patients regardless of the level of pneumonia (mild, severe, or symptom-free) as compared with healthy controls (p < 0.05). In addition, the number of Tc17 (CD3+, CD8+, and IL-17A+) cells increased in low pneumonia and severe pneumonia groups compared with the healthy controls (p < 0.05). Both IL-22 and IL-17A production decreased during a follow-up within 6 weeks of discharge. Our findings suggest that the increase in only IL-22 expressed Tc22 cells in the 0-12 age group with a general symptom-free course and higher levels of Th22 and Tc22 in uncomplicated adult cases may indicate the protective effect of IL-22. On the contrary, the association between the severity of pneumonia and the elevation of Tc17 cells in adults may reveal the damaging effect of IL-22 when it is co-expressed with IL-17.

Interleukin-4 gene polymorphisms confer Behçet's disease in Turkish population.

Several cytokine genes may play crucial roles in host susceptibility to Behçet's Disease (BD), because the cytokine production capacity varies among individuals and depends on the cytokine gene polymorphisms. The association of the IL-4 and IL-4Rα gene polymorphisms with the susceptibility to BD was investigated in this study. DNA samples were obtained from a Turkish population of 97 patients with BD and 76 healthy control subjects. All genotyping (IL-4 and IL-4Rα) experiments were performed using PCR sequence-specific primers. When compared with the healthy controls, the frequency of IL-4 -1098 TG and -590 CT genotypes was higher in the patients with BD. Analysis of allele frequencies showed that IL-4 -1098 G and IL-4 -590 T alleles were more common in the patients with BD when compared with healthy controls. Also, IL-4 TTC and haplotypes were found to confer BD. Interestingly, we demonstrated that IL-4Rα gene polymorphism seems to be associated with the Pathergy test positivity in patients with BD. Our data suggest that IL-4 gene promoter polymorphisms may affect susceptibility to BD and increase risk of developing the disease. However, in order to confirm and assess the association of IL-4 and IL-4Rα gene polymorphisms with the BD, large cohort studies are needed.

IL-1 cluster gene polymorphisms in Turkish patients with Behçet's disease.

Several cytokine genes may play crucial roles in host susceptibility to Behçet's Disease (BD), since the cytokine production capacity varies among individuals and depends on the cytokine gene polymorphisms. The association of the IL-1 cluster gene polymorphisms with the development of BD was investigated in this study. DNA samples were obtained from a Turkish population of 97 patients with BD, and 77 healthy control subjects. All genotyping (IL-1α, IL-1ß, IL-1R and IL-1Ra) experiments were performed using sequence specific primers PCR (PCR-SSP). When compared to the healthy controls, the frequencies of IL-1Ra IL-1α and IL-1R gene polymorphisms were not significantly different in BD patients. The frequency of IL-1ß-511 TT genotype was higher in the BD group in comparison to the control group. Interestingly, we demonstrated that IL-1 ß +3962 gene polymorphism seems to be associated with the presence of Erythema nodosum in BD patients. Our data suggest that polymorphisms in IL-1ß gene may affect host susceptibility to BD. In order to confirm the biological significance of our results, further studies should be performed in a large-scale study and/or in different ethnic groups.

Melatonin modulates hippocampus NMDA receptors, blood and brain oxidative stress levels in ovariectomized rats.

We investigated the effects of melatonin administration on ovariectomy-induced oxidative toxicity and N-methyl-D: -aspartate receptor (NMDAR) subunits in the blood of rats. Thirty-two rats were studied in three groups. The first and second groups were control and ovariectomized rats. Melatonin was daily administrated to the ovariectomized rats in the third group for 30 days. Blood, brain cortical and hippocampal samples were taken from the three groups after 30 days. Brain cortical, erythrocyte and plasma lipid peroxidation (LP) levels were higher in the ovariectomized group than in controls, although the LP level was decreased in the ovariectomized group with melatonin treatment. Brain cortical and plasma concentrations of vitamins A, C and E as well as the NMDAR 2B subunit were lower in the ovariectomized group than in controls, although, except for plasma vitamin C, they were increased by the treatment. Brain cortical and erythrocyte reduced glutathione (GSH) levels were lower in the ovariectomized group than in controls, although erythrocyte GSH levels were higher in the melatonin group than in the ovariectomized group. Brain cortical and erythrocyte glutathione peroxidase activity and NMDAR 2A subunit concentrations were not found to be different in all groups statistically. Oxidative stress has been proposed to explain the biological side effect of experimental menopause. Melatonin prevents experimental menopause-induced oxidative stress to strengthen antioxidant vitamin and NMDAR 2A subunit concentrations in ovariectomized rats.

Sensitivity and specificity of infrared thermography in detection of subclinical mastitis in dairy cows.

The objectives of this experiment were to determine interrelationships among mastitis indicators and evaluate the subclinical mastitis detection ability of infrared thermography (IRT) in comparison with the California Mastitis Test (CMT). Somatic cell count (SCC), CMT, and udder skin surface temperature (USST) data were compiled from 62 Brown Swiss dairy cows (days in milk=117+/-51, milk yield=14.7+/-5.2 kg; mean +/- SD). The CORR, REG, and NLIN procedures of Statistical Analysis System (SAS Institute Inc., Cary, NC) were employed to attain interrelationships among mastitis indicators. The diagnostic merit of IRT as an indirect measure of subclinical mastitis was compared with CMT using the receiver operating characteristics curves. The udder skin surface temperature was positively correlated with the CMT score (r=0.86) and SCC (r=0.73). There was an exponential increase in SCC (SCC, x10(3) cells/mL=22.35 x e(1.31 x CMT score); R(2)=0.98) and a linear increase in USST (USST, degrees C=33.45+1.08 x CMT score; R(2)=0.75) as the CMT score increased. As SCC increased, USST increased logarithmically [USST, degrees C=28.72+0.49 x ln(SCC, x10(3) cells/mL); R(2)=0.72]. The USST for healthy quarters (SCC 400,000 cells/mL; n=135) (mean +/- SE; 33.45+/-0.09 vs. 35.80+/-0.08 degrees C). The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, and negative predictive value were 95.6, 93.6, 14.97, 0.05, 95.0, and 93.6, respectively, for IRT and 88.9, 98.9, 83.56, 0.11, 99.2, and 86.1, respectively, for CMT. The area under the receiver operating characteristics curve for IRT and CMT was not different. In conclusion, as a noninvasive and quick tool, IRT can be employed for screening subclinical mastitis via measuring USST, with a high predictive diagnostic ability similar to CMT when microbiological culturing is unavailable. However, the reliability of IRT among cows with different characteristics and those living under various environmental conditions remains to be determined.

Frontiers in clinical immunology 2008.

In recent years, investigations in immunology have led to progress in clinical medicine, including understanding transplant rejection, autoimmune diseases, immune deficiencies, inflammation, transplantation, cancer and the development of new vaccines. At a meeting recently held on the Mediterranean shore, advances in several facets of clinical immunology were the focus of discussion. Here, we highlight some of the debates that reflected advances in a variety of human immune disorders.

Cytokine gene polymorphisms in Behçet's disease and their association with clinical and laboratory findings.

The association of the cytokine gene polymorphisms with the development of Behçet's Disease (BD) was investigated in this study. DNA samples were obtained from a Turkish population of 97 unrelated patients with BD, and 127 unrelated healthy control subjects.All genotyping (IL-6, IL10, IFN-gamma, TGF-Beta1 and TNF-alpha) experiments were performed using sequence-specific primers PCR. The frequency of TGF-Beta1 codon 25 GG genotype was found significantly lower in BD patients compared to healthy control subjects. The IL-10 -1082 GA genotype was more frequent whereas the AA genotype was less common in the BD group compared to the control group. The association between clinial findings and cytokine gene polymorphisms was further investigated in the patients with BD. The frequency of IFN-gamma AA genotype was lower in the patients with genital ulcer. Additionally, it was found that the frequency of IL-6 -174 GG genotype was lower in the patients with Pathergy positivity. These results suggest that TGF-Beta1 and IL-10 gene polymorphisms may affect host susceptibility to BD. Also, to confirm the biological significance of our results, further studies should be performed on other population groups and in large number of cases.

The involvement of IL-10, IL-6, IFN-gamma, TNF-alpha and TGF-beta gene polymorphisms among Turkish lung cancer patients.

Several genes encoding different cytokines may play crucial roles in host susceptibility to lung cancer, since cytokine production capacity varies among individuals and depends on cytokine gene polymorphisms. The association between cytokine gene polymorphisms with primary lung carcinoma was investigated. DNA samples were obtained from a Turkish population of 44 patients with primary lung cancer, and 59 healthy control subjects. All genotyping (IFN-gamma, TGF-beta1, TNF-alpha, IL-6 and IL-10) experiments were performed using sequence-specific primers (SSP)-PCR. When compared to the healthy controls, the frequencies of high/intermediate producing genotypes of IL-10 and low producing genotype of TNF-alpha were significantly more common in the patient group. It is noteworthy that lung cancer patients with the TGF-beta T/T genotype in codon 10 had statistically longer survival compared to those having the C/C genotype (Kaplan-Meier survival function test, log rank significance = 0.014). These results suggest that IL-10, TNF-alpha and TGF-beta1 gene polymorphisms may affect host susceptibility to lung cancer and the outcome of the patients.

MicroRNA Expression Patterns of CD8+ T Cells in Acute and Chronic Brucellosis.

Although our knowledge about Brucella virulence factors and the host response increase rapidly, the mechanisms of immune evasion by the pathogen and causes of chronic disease are still unknown. Here, we aimed to investigate the immunological factors which belong to CD8+ T cells and their roles in the transition of brucellosis from acute to chronic infection. Using miRNA microarray, more than 2000 miRNAs were screened in CD8+ T cells of patients with acute or chronic brucellosis and healthy controls that were sorted from peripheral blood with flow cytometry and validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Expression of two miRNAs were determined to display a significant fold change in chronic group when compared with acute or control groups. Both miRNAs (miR-126-5p and miR-4753-3p) were decreased (p <0.05 or fold change > 2). These miRNAs have the potential to be the regulators of CD8+ T cell-related marker genes for chronic brucellosis infections. The differentially expressed miRNAs and their predicted target genes are involved in MAPK signaling pathway, cytokine-cytokine receptor interactions, endocytosis, regulation of actin cytoskeleton, and focal adhesion indicating their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human CD8+ T cells to clarify the mechanism of inveteracy in brucellosis.

Effects of digoxin on acute, atrial fibrillation-induced changes in atrial refractoriness.

BACKGROUND: Atrial fibrillation (AF) shortens the atrial effective refractory period (ERP) and predisposes to further episodes of AF. The acute changes in atrial refractoriness may be related to tachycardia-induced intracellular calcium overload. The purpose of this study was to determine whether digoxin, which increases intracellular calcium, potentiates the acute effects of AF on atrial refractoriness in humans. METHODS AND RESULTS: In 38 healthy adults, atrial ERP was measured at basic drive cycle lengths (BDCLs) of 350 and 500 ms after autonomic blockade. Nineteen patients had been treated with digoxin for 2 weeks. After a several-minute episode of AF, atrial ERP was measured serially at alternating BDCLs. Compared with pre-AF ERPs, the first post-AF ERPs were significantly shorter in both the digoxin and the control groups (P:<0.001). The post-AF ERP at a BDCL of 350 ms shortened to a greater degree in the digoxin group (37+/-16 ms) than in the control group (20+/-13 ms, P:<0.001); similar changes occurred at a BDCL of 500 ms. During post-AF determinations of the atrial ERP, secondary AF episodes occurred significantly more often in the digoxin group (32% versus 16%; P:<0. 04). CONCLUSIONS: After a brief episode of AF, digoxin augments the shortening that occurs in atrial refractoriness and predisposes to the reinduction of AF. These effects occur in the setting of autonomic blockade and therefore are more likely to be due to the effects of digoxin on intracellular calcium than to its vagotonic effects.

Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD).

OBJECTIVES: This study sought to assess proinflammatory cytokine levels in patients in the studies of left ventricular dysfunction trial (SOLVD) in relation to both their New York Heart Association functional classification and their neurohormonal status before randomization. BACKGROUND: Elevated levels of tumor necrosis factor-alpha have been identified in 30% to 40% of patients with heart failure. However, it is unclear which subsets of patients with heart failure elaborate tumor necrosis factor-alpha. It is also unclear what the mechanism for the increased expression of proinflammatory cytokines is. METHODS: Tumor necrosis factor-alpha and interleukin-6 levels were analyzed by enzymes-linked immunoassay using randomly selected plasma samples from patients in functional classes I to III who were enrolled in neurohormonal substudies of the SOLVD trial; age-matched healthy subjects served as the control group. RESULTS: Plasma levels of tumor necrosis factor-alpha (p < 0.001) were elevated in patients in functional classes I to III ([mean +/- SD] 1.95 +/- 0.54, 2.63 +/- 0.48, 6.4 +/- 1.9 pg/ml, respectively) compared with age-matched control subjects (0.75 +/- 0.05 pg/ml) and were progressively elevated in relation to decreasing functional status of the patient. Plasma levels of interleukin-6 (p < 0.001) were elevated in patients in functional classes I to III (3.3 +/- 0.55, 6.2 +/- 1.1, 5.22 +/- 0.9 pg/ml, respectively) compared with age-matched control subjects (1.8 +/- 0.5 pg/ml and were progressively elevated in relation to decreasing functional status of the patient. Cox proportional-hazards analysis showed that there was a trend toward significance between plasma tumor necrosis factor-alpha (p < 0.07) and survival, whereas there was no significant relation for plasma interleukin-6 (p < 0.72). Except for atrial natriuretic factor, which correlated weakly (r = 0.23, p = 0.04) with circulating tumor necrosis factor-alpha levels, there was no significance correlation between neurohormonal and proinflammatory cytokine levels. CONCLUSIONS: Circulating levels of proinflammatory cytokines increase in patients as their functional heart failure classification deteriorates. Moreover, activation of the neurohumoral axis is unlikely to completely explain the elaboration of proinflammatory cytokines in heart failure.

Double potentials along the ablation line as a guide to radiofrequency ablation of typical atrial flutter.

OBJECTIVES: The purpose of this study was to determine the characteristics of double potentials (DPs) that are helpful in guiding ablation within the cavo-tricuspid isthmus. BACKGROUND: Double potentials have been considered a reliable criterion of cavo-tricuspid isthmus block in patients undergoing radiofrequency ablation of typical atrial flutter (AFL). However, the minimal degree of separation of the two components of DPs needed to indicate complete block has not been well defined. METHODS: Radiofrequency ablation was performed in 30 patients with isthmus-dependent AFL. Bipolar electrograms were recorded along the ablation line during proximal coronary sinus pacing at sites at which radiofrequency ablation resulted in incomplete or complete isthmus block. RESULTS: Double potentials were observed at 42% of recording sites when there was incomplete isthmus block, compared with 100% of recording sites when the block was complete. The mean intervals separating the two components of DPs were 65 +/- 21 ms and 135 +/- 30 ms during incomplete and complete block, respectively (p < 0.001). An interval separating the two components of DPs (DP(1-2) interval) <90 ms was always associated with a local gap, whereas a DP(1-2) interval > or =110 ms was always associated with local block. When the DP(1-2) interval was between 90 and 110 ms, an isoelectric segment within the DP and a negative polarity in the second component of the DP were helpful in indicating local isthmus block. A DP(1-2) interval > or =90 ms with a maximal variation of 15 ms along the entire ablation line was an indicator of complete block in the cavo-tricuspid isthmus. CONCLUSIONS: Detailed analysis of DPs is helpful in identifying gaps in the ablation line and in distinguishing complete from incomplete isthmus block in patients undergoing radiofrequency ablation of typical AFL.