scholarly journals Modulation of Airway Inflammation by Immunostimulatory CpG Oligodeoxynucleotides in a Murine Model of Allergic Aspergillosis

2004 ◽  
Vol 72 (10) ◽  
pp. 6087-6094 ◽  
Author(s):  
Banani Banerjee ◽  
Kevin J. Kelly ◽  
Jordan N. Fink ◽  
James D. Henderson ◽  
Naveen K. Bansal ◽  
...  

ABSTRACT Allergic aspergillosis is a Th2 T-lymphocyte-mediated pulmonary complication in patients with atopic asthma and cystic fibrosis. Therefore, any therapeutic strategy that selectively inhibits Th2 T-cell activation may be useful in downregulating allergic lung inflammation in asthma. In the present study, we developed a CpG oligodeoxynucleotide (ODN)-based immune intervention of allergic inflammation in a mouse model of allergic aspergillosis. Four different groups of mice were used in a short-term immunization protocol. Three experimental groups of animals (groups 1 to 3) were sensitized with Aspergillus fumigatus antigens. Animals in group 1 were immunized with A. fumigatus antigen alone, while those in group 2 were treated with CpG-ODN 1 day before the first antigen immunization, and the animals in group 3 received the first CpG-ODN administration between the antigen treatments. The animals in group 4 served as controls and were given phosphate-buffered saline. Allergen-specific serum immunoglobulins and total immunoglobulin E in different groups of animals were measured by enzyme-linked immunosorbent assay, while airway remodeling and cytokine production were studied by immunohistochemistry. The results demonstrated that CpG-ODN administration either before (group 2) or between (group 3) antigen treatments resulted in reduced total immunoglobulin E levels and peripheral blood eosinophil numbers compared to A. fumigatus allergen-sensitized group 1 animals. Similarly, treatment with CpG-ODN also downregulated inflammatory cell infiltration, goblet cell hyperplasia, and basement membrane thickening compared to A. fumigatus-sensitized mice. The distinct reduction in peripheral blood eosinophilia and airway remodeling in CpG-ODN-treated mice emphasized its usefulness as an immunomodulating agent for allergic fungal diseases.

2011 ◽  
Vol 30 (10) ◽  
pp. 1644-1648 ◽  
Author(s):  
Vefik Arica ◽  
Murat Tutanc ◽  
Oktay Hasan Ozturk ◽  
Secil Arica ◽  
Fatmagul Basarslan ◽  
...  

Aim: In the study, we examined erdosteine’s effects on platelet functions and coagulation. Materials and methods: A total 29 young albino Wistar rats were divided into four groups. Control rats ( n = 6) were given saline; Group 1 rats ( n = 7) were given 3 mg/kg erdosteine by oral gavage for 3 days; Group 2 rats ( n = 7) were given 10 mg/kg erdosteine by oral gavage for 3 days; and Group 3 rats ( n = 9) were given 30 mg/kg erdosteine for 3 days. Twenty-four hours after the final dose, blood samples were drawn from a portal vein. Prothrombin time (PT), activated partial thromboplastin time (aPTT) and international normalized ratio (INR) were measured, and platelet counts were examined in a peripheral blood smear by light microscopy. Results: PT and INR values of Group 1 increased compared to the controls but did not change in Group 3. Hemostatic parameters were not measured in Group 2 because the blood samples in Group 2’s tubes clotted rapidly. Platelet counts of the peripheral blood from Group 2 were low but were normal in other groups. Conclusion: We have concluded erdosteine may disrupt hemostasis parameters by its different metabolites in patients. Erdosteine has dual effects on hemostasis via its different metabolites, which occur in different doses.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5328-5328
Author(s):  
Carolyn L. Bigelow ◽  
Stephanie L. Elkins ◽  
Cheryl L. Hardy ◽  
Joe C. Files

Abstract Our stem cell transplant program treats a spectrum of hematologic malignancies that includes a number of patients with high risk myeloid disease. These challenging patients have lead our adult allotransplant program to employ alternative approaches to standard conditioning over the last three years using reduced intensity conditioning. The regimens are amenable to modification, allowing a goal of maximizing length of remission or period of low tumor burden while minimizing transplant-related mortality. We have conducted a retrospective study of patients receiving modified reduced intensity regimens of fludarabine, melphalan and Campath. Incidence of relapse, survival, tempo of engraftment and incidence of grades I–II and III–IV acute GVHD were compared. Three modifications of the regimen were: fludarabine 30 mg/m2 x 5d, melphalan 140 mg/m2 x 1d, Campath 20 mg/d x 5 days (Group 1); fludarabine and melphalan the same and Campath 20 mg/d x 3d (Group 2); fludarabine and melphalan the same and Campath 20 mg/d x 1d (Group 3). Fifteen patients with a median age of 48, range 24 to 58 years, were in the study. Twelve patients had AML, two had CML and one had MDS. Six patients were in CR at time of transplant and nine had detectable tumor or disease. Patients were not randomized for a conditioning group but were transplanted in a consecutive fashion; seven patients were in Group 1, five patients in Group 2 and three patients in Group 3. Stem cell sources were related BM for four recipients, related peripheral blood for one, unrelated BM for four, unrelated peripheral blood for four, a combination of related BM and peripheral blood for one, and one cord blood. All patients received an adequate CD34+ cell dose and none of the products was manipulated. Match grade was 6/6 for 13 transplants, 5/6 for one and 4/6 for the cord blood transplant. GVHD prophylaxis was the same for all recipients (standard dose cyclosporine or tacrolimus and MMF) tapering after day 30. No failures to achieve a WBC graft, including the cord blood recipient, occurred. Neutrophils (ANC >500/dl) engrafted at a median of day 13 (range 10 – 48 days). Median follow-up was seven months (range 1.5 – 30 months). Two patients in Group 1 had grade I aGVHD and one continued to chronic GVHD. One patient in Group 2 had grade II and one had grade III aGVHD. None in Group 3 had aGVHD. Relapse occurred in three patients in Group 1 and they received DLI immunotherapy; no relapse occurred in Group 2 or 3. Twelve patients survived to day 100; three from Groups 1 or 2 did not. Four were alive at one year and four others who are still alive have not reached the one year mark. Four of the seven patients who have died were from residual disease; the other three were from treatment-related toxicity within the first 100 days. Eight of 15 patients remain in follow-up. We conclude that the application of fludarabine, melphalan, Campath conditioning regimens has been successful in this high risk group of patients. The cell source from an unrelated or related donor does not impact outcomes. There was a very low incidence of toxicity related to aGVHD, no failure to engraft and no unexpected complications. Lastly, this regimen has allowed modification to enhance its tumoricidal properties to the extent that these patients with myeloid disease have experienced a low 20% incidence of relapse. We will continue to modify and expand the patient selection criteria to elderly (< 70 years old) AML in remission.


2014 ◽  
Vol 21 (5) ◽  
pp. 636-640 ◽  
Author(s):  
Lourdes R. A. Vaz-de-Lima ◽  
Monte D. Martin ◽  
Lucia C. Pawloski ◽  
Daniela Leite ◽  
Karen C. P. Rocha ◽  
...  

ABSTRACTPertussis remains an important public health problem in many countries despite extensive immunization. Cultures and real-time PCR (RT-PCR) assays are the recommended pertussis diagnostic tests, but they lack sensitivity at the later stage of the disease. This study introduces the IgG anti-pertussis toxin enzyme-linked immunosorbent assay (PT ELISA) in our routine diagnosis to improve disease burden estimation. Serum samples and nasopharyngeal swabs (n= 503) were collected at the same time from patients presenting with cough illness suspected of being pertussis and tested by the PT ELISA and culture and/or RT-PCR, respectively. Patients were separated into three age groups: group 1, <1 year (n= 260; mean age, 3 months), group 2, 1 to 6 years (n= 81; mean age, 3 years), and group 3, ≥7 years (n= 162; mean age, 26 years). The times (means) from cough onset to specimen collection were 16, 24, and 26 days, respectively. In group 1, 83 (82.2%) of 101 positive cases were positive for pertussis by culture/RT-PCR, while 40 (39.6%) tested positive by PT ELISA. In group 2, 6 (19.4%) of 31 positive cases were culture/RT-PCR positive, and 29 (93.6%) were seropositive. In group 3, 13 (13.8%) of 94 positive cases were positive by culture/RT-PCR and 91 (96.8%) were positive by serology. Culture/RT-PCR detected more cases of pertussis in infants (P< 0.0001), whereas the PT ELISA detected more cases in adolescents and adults (P< 0.0001). The timing between cough onset and specimen collection or recent vaccination may have partially affected our results. Serology is a suitable, cost-effective, and complementary pertussis diagnostic tool, especially among older children, adolescents, and adults during the later disease phase.


Author(s):  
Turgut Burak ◽  
Mercan Kadir ◽  
Demir Nesrin ◽  
Ilhan Nevin ◽  
Çatak Onur

Purpose: To evaluate the levels of salusin-beta (β-SAL) in the serum in patients with age-related macular degeneration (ARMD). Methods: Our study was designed as a controlled comparative clinical study. The β-SAL levels in serums of age and sex-matched 20 healthy volunteers as controls (Group 1), 20 patients with dry-age related macular degeneration (d-ARMD) (Group 2) and 20 patients with wet-age related macular degeneration (w-ARMD) (Group 3) were measured with the enzyme-linked immunosorbent assay (ELISA) method. Results: In our study, it was found that age and gender didn’t show a statistically significant difference among the study groups (p > 0. 05). The mean serum β-SAL levels in Group 1, Group 2 and Group 3 were 1372,17 ± 1126.69 pg/mL; 1423,71 ± 1196.84 pg/mL and 940,57 ± 1092.05 pg/mL, respectively. Although the meanβ-SAL levels in w-ARMD seem numerically lower than both the control and d-ARMD groups, this difference among the study groups was not statistically significant (p > 0.05). Conclusion: Our study suggests that β-SAL levels in the patients with ARMD and healthy controls were not different than each other. Further studies with large numbers may reveal possible relationships between β-SAL and ARMD.


2012 ◽  
Vol 32 (6) ◽  
pp. 383-388 ◽  
Author(s):  
N.M. Raghavendra ◽  
A.R. Pradeep ◽  
Rahul Kathariya ◽  
Anuj Sharma ◽  
Nishanth S. Rao ◽  
...  

Visfatin is a pleiotropic mediator which acts as growth factor, cytokine, enzyme involved in energy including nicotinamide adenine dinucleotide metabolism and has been recently demonstrated to exert several pro-inflammatory functions. The purpose of this study is to evaluate the Visfatin concentration in gingival crevicular fluid (GCF) and serum in patients with chronic periodontitis, and to evaluate the effect of non-surgical periodontal therapy on the GCF and serum visfatin concentration. 30 subjects (age range: 25 to 52 years) were selected and divided into two groups based on the gingival index, probing depth, periodontal attachment level, and radiologic parameters (bone loss): group 1 (15 subjects with healthy periodontium), group 2 (15 subjects with chronic periodontitis), while, Group 2 patients after 8 weeks of the treatment (scaling and root planning, SRP) constituted group 3. GCF samples (by microcapillary pipettes) and serum samples (by venipuncture) were collected to estimate the levels of Visfatin using enzyme linked immunosorbent assay kit. The mean Visfatin concentration in GCF and serum was observed to be the highest in group 2 and lowest in group 1. While concentration in group 3 was similar to group 1. The concentration of Visfatin in GCF and serum decreased after SRP. The Visfatin concentration in GCF and serum found to be highest in chronic periodontitis group and decreases after treatment. Hence Visfatin values can be considered as an “inflammatory marker” can be explored in future as a potential therapeutic target in the treatment of periodontal disease.


1995 ◽  
Vol 3 (5) ◽  
pp. 179-183 ◽  
Author(s):  
Kimberly A. Heller ◽  
Phillip C. Greig ◽  
R. Phillip Heine

Objective:Lactoferrin is a glycoprotein released from the secondary granules of activated neutrophils in the setting of infection. The purpose of this study was to determine if amniotic-fluid (AF) lactoferrin levels are elevated in preterm labor (PTL) patients with subclinical intraamniotic infection (IAI).Methods:AF samples were obtained from 186 pregnant patients with the following characteristics: group 1 - term, no labor; group 2 - preterm, no labor; group 3 - PTL with IAI; group 4 - PTL without IAI. Lactoferrin levels were measured with an enzyme-linked immunosorbent assay (ELISA).Results:AF lactoferrin levels were elevated in normal gestation after 31 weeks (P < 0.0001). Lactoferrin levels were also higher in infected PTL patients compared with noninfected PTL patients at gestations ≤31 weeks (P = 0.005). An AF lactoferrin level of >2.5 μg/ml is highly suggestive of infection in PTL patients at <32 weeks, with an overall sensitivity of 82% and a specificity of 83%, when infection is defined as a positive AF culture or positive placental histology.Conclusions:AF lactoferrin levels increase after 31 weeks in normal gestations, but lactoferrin levels >2.5 μg/ml in PTL patients before this gestational age are highly suggestive of IAI. AF lactoferrin levels may be a useful clinical tool for selecting those PTL patients who might benefit from antimicrobial therapy, closer observation, or early delivery.


2021 ◽  
Vol 23 (5) ◽  
pp. 608-613
Author(s):  
H. P. Kuzmina ◽  
O. M. Lazarenko

The aim. To analyze the frequency of atherosclerotic lesions of the carotid arteries and association with the lipid metabolism and inflammatory markers in hypertensive patients with gout. Materials and methods. 122 patients with hypertension aged 30 to 65 years were examined (mean age (56.0 (47.0; 62.0)), inclu­ding 104 men (85.2 %) and 18 women (14.8 %). Group 1 included 72 hypertensive patients with gout; group 2 – 50 hypertensive patients without gout; group 3 – 20 gout patients without hypertension. Serum levels of high sensitivity C-reactive protein were detected by enzyme-linked immunosorbent assay. Serum ferritin levels were measured using electrochemiluminescent detection. The patients underwent carotid artery ultrasound according to standard methods. Results. The duration of gout exacerbation and the pain intensity evaluated with the visual analog scale (VAS) (P < 0.01) were significantly higher in group 1, than those in group 3 (P < 0.01). Serum ferritin levels were 2.6 (P < 0.01) times higher in group 1 than those in group 2. In patients with gout, the levels of ferritin were significantly 2.1 times higher, than in group 2 (P < 0.01). The levels of hsСRP in patients of group 1 were 3.1 times higher than those in group 2 (P < 0.01). The proportion of patients with intima-media complex (IMC) thickness ≥0.9 mm was higher in group 1 than in groups 2 (χ2 = 4.58, P < 0.05) and 3 (χ2 = 24.96, P < 0.01). In the structure of plaques, isoechoic were significantly more often seen among group 1 patients as compared to group 3 (χ2 = 6.56, P < 0.01), and hyperechoic – as compared to group 2 (χ2 = 4.63, P < 0.05). Hypoechoic plaques were detected in groups 1 and 2 with similar frequency (P > 0.05). This type of plaque was associated with a high risk of cerebrovascular events. In the patients with arterial hypertension and gout, a significant moderate positive correlation was found between the IMC thickness and the serum uric acid level (rs = 0.46, P < 0.01), hsCRP (rs = 0.33, P < 0.01), age (rs = 0.33; P < 0.01), duration of gout (rs = 0.27, P < 0.05) and VAS (rs = 0.39, P < 0.01); the level of hsCRP was correlated with the presence of atherosclerotic plaques (τ = +0.64, P < 0.05). Conclusions. The combination of hypertension with gout in patients was associated with a high incidence of IMC thickness ≥0.9 mm and atherosclerotic plaques, more severe disorders of purine and lipid metabolism, increased inflammatory markers (ferritin and hsCRP), that should be considered not only in the aspect of chronic inflammation, but also as a part of the disease.


2019 ◽  
Vol 34 (6) ◽  
pp. 309-312 ◽  
Author(s):  
Senem Ayça ◽  
Halil Ural Aksoy ◽  
İsmail Taştan ◽  
Muzaffer Polat

Levels of melatonin have been reported before in children with epilepsy, but such has not been reported to date in those with continuous spikes and waves during sleep. The aim of the present study was to assess serum melatonin levels and melatonin circadian rhythm in patients with continuous spikes and waves during sleep and epilepsy. Serum melatonin was measured in 39 children stratified into 3 groups. Group 1 included 15 patients with continuous spikes and waves during sleep, group 2 included 12 epilepsy patients, and group 3 included 12 controls, respectively. Blood samples were taken from all participants at 1:00 am and 9:00 am and melatonin levels were measured using a quantitative enzyme-linked immunosorbent assay test. The 9:00 am melatonin levels of group 1 were significantly decreased and pair groups were compared. The Pa value (representing a comparison between groups 1 and 2) was .002, the Pb value (representing a comparison between groups 1 and 3) was .001, and the Pc value (representing a comparison between groups 2 and 3) was .86. These findings suggest that the 9:00 am melatonin levels were significantly decreased in the comparison of groups 2 and 3. Further detailed research is necessary to determine the factors leading to the rapid decline of morning melatonin levels of children with continuous spikes and waves during sleep.


VASA ◽  
2020 ◽  
Vol 49 (4) ◽  
pp. 281-284
Author(s):  
Atıf Yolgosteren ◽  
Gencehan Kumtepe ◽  
Melda Payaslioglu ◽  
Cuneyt Ozakin

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.


1984 ◽  
Vol 52 (03) ◽  
pp. 253-255 ◽  
Author(s):  
C Isles ◽  
G D O Lowe ◽  
B M Rankin ◽  
C D Forbes ◽  
N Lucie ◽  
...  

SummaryWe have previously shown abnormalities of haemostasis suggestive of intravascular coagulation in patients with malignant hypertension, a condition associated with retinopathy and renal fibrin deposition. To determine whether such abnormalities are specific to malignant hypertension, we have measured several haemostatic and haemorheological variables in 18 patients with malignant hypertension (Group 1), 18 matched healthy controls (Group 2), and 18 patients with non-malignant hypertension (Group 3) matched for renal pathology, blood pressure and serum creatinine with Group 1. Both Groups 1 and 3 had increased mean levels of fibrinogen, factor VIIIc, beta-thrombo- globulin, plasma viscosity and blood viscosity (corrected for haematocrit); and decreased mean levels of haematocrit, antithrombin III and platelet count. Mean levels of fast antiplasmin and alpha2-macroglobulin were elevated in Group 1 but not in Group 3. We conclude that most blood abnormalities are not specific to malignant hypertension; are also present in patients with non-malignant hypertension who have similar levels of blood pressure and renal damage; and might result from renal damage as well as promoting further renal damage by enhancing fibrin deposition. However increased levels of fibrinolytic inhibitors in malignant hypertension merit further investigation in relation to removal of renal fibrin.


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