Anti-inflammatory iron chelator, DIBI, reduces leukocyte-endothelial adhesion and clinical symptoms of LPS-induced interstitial cystitis in mice

2021 ◽  
Vol 79 (3) ◽  
pp. 395-406
Author(s):  
Georg Hagn ◽  
Bruce Holbein ◽  
Juan Zhou ◽  
Christian Lehmann
Keyword(s):  
Interstitial Cystitis ◽  
Intravital Microscopy ◽  
Iron Chelator ◽  
Capillary Density ◽  
Control Group ◽  
Pain Response ◽  
Leukocyte Activation ◽  
Gram Negative ◽  
Pain And Suffering ◽  
Adherent Leukocytes

BACKGROUND: Interstitial cystitis (IC) is a prevalent and debilitating chronic inflammatory disease of the urinary bladder. Currently there are no fully effective therapeutic agents available, in part due to the still obscure pathogenesis of IC. Lipopolysaccharide (LPS) also known as endotoxin from Gram negative bacteria elicits IC in mice and has formed the basis of model systems for investigation. Excess free iron plays an important role in inflammation through generation of reactive oxygen species (ROS). The novel iron chelator DIBI has been shown to sequester excess free iron and dampen excess inflammatory responses to systemic LPS administration and also to Gram negative bacterial infections. OBJECTIVE: The overall objective of this study was to evaluate the effects of DIBI on LPS induced IC in mice. Leukocyte activation, endothelial adhesion and functional capillary density were assessed by intravital microscopy of the bladder microcirculation following a single intravesical LPS administration with or without intravesical DIBI treatment. Clinical IC symptoms were also assessed through behavioral and pain threshold force measurements. METHODS: Four groups of female BALB/c mice (n = 5–6/group) were randomized in this study: control group, IC group without therapy, IC group with DIBI therapy and control group with DIBI therapy. The groups were examined using intravital microscopy (IVM) of the bladder for leukocyte-endothelial interactions (adherent leukocytes, temporarily interacting leukocytes) and functional capillary density (FCD). A modified behavioral score by Boucher et al. and Von-Frey-Aesthesiometry were used to evaluate key behavioral indices related to pain and visceral pain perception. RESULTS: LPS introduced intravesically induced an early (≤2h) inflammation of the bladder evidenced by leukocyte activation and adhesion to bladder capillary walls. Intravesical DIBI therapy of mice 30min following LPS administration and assessed after 1.5h treatment showed a significant decrease in the number of adherent leukocytes compared to IC animals without DIBI treatment. DIBI treated mice showed a significantly lowered increase in behavioral distress scores compared to IC mice without therapy. Untreated IC mice exhibited a significantly decreased threshold force value for evoked pain response and DIBI treatment improved the threshold pain response. A significant inverse correlation was found for the two pain and suffering evaluation methods results. CONCLUSION: DIBI reduced inflammatory endothelial leukocyte adhesion and key indices related to pain and suffering over those observed in untreated IC mice. Our findings suggest a potential therapeutic role for DIBI for IC treatment.

scholarly journals Bradykinin Antagonists Reduce Leukocyte–Endothelium Interactions after Global Cerebral Ischemia

2003 ◽  
Vol 23 (4) ◽  
pp. 441-448 ◽  
Author(s):  
Jens Lehmberg ◽  
Jürgen Beck ◽  
Alexander Baethmann ◽  
Eberhard Uhl
Keyword(s):  
Cerebral Ischemia ◽  
Functional Outcome ◽  
Intravital Microscopy ◽  
Global Cerebral Ischemia ◽  
Mongolian Gerbils ◽  
Leukocyte Activation ◽  
Cerebral Microcirculation ◽  
Receptor Antagonists ◽  
Bradykinin Antagonists ◽  
Adherent Leukocytes

The aim of the present study was to evaluate the influence of bradykinin on microcirculatory changes and outcome after global cerebral ischemia (15 minute) in Mongolian gerbils. The cerebral microcirculation was investigated by fluorescent intravital microscopy. Survival and functional outcome was evaluated up to 4 d after ischemia. Animals were treated with the selective B1 and B2 receptor antagonists B 9858 and CP 0597, respectively, and the nonselective B1/B2 receptor antagonist B 9430. Leukocyte activation was significantly reduced by all antagonists as indicated by a significant decrease in the number of rolling (33 ± 20, 6 ± 8, 9 ± 10, and 13 ± 10) and adherent leukocytes (9 ± 7, 3 ± 4, 1 ± 1, and 2 ± 3 · 100 μm–1 · min–1 in controls and in animals treated with B1, B2, and B1/B2 antagonist, respectively). Arteriolar diameters were significantly reduced during reperfusion (35 ± 11 before and 27 ± 8 μm 40 minutes after ischemia) in animals treated with the B2 antagonist. The postischemic hypoperfusion, however, was not affected. Mortality was significantly higher in animals treated with the B1 and the B1/B2 antagonist. The authors concluded that bradykinin is involved in postischemic disturbances of cerebral microcirculation. The therapeutic effect of specific bradykinin receptor antagonists on functional outcome, however, remains unclear.

Clinical-Reported Outcomes Of Deferoxamine Versus Deferasirox In The Treatment Of Homozygous BetaThalassemia

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Zeina A Munim Al-Thanoon ◽  
Zeina A Munim Al-Thanoon ◽  
Mustafa Basil ◽  
Nasih A Al-Kazzaz
Keyword(s):  
Serum Ferritin ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Beta Thalassemia ◽  
Control Group ◽  
Current Standard ◽  
Cross Sectional ◽  
Significant Difference ◽  
Multiple Blood ◽  
Group 2

Iron chelation therapy with deferoxamine (DFO),the current standard for the treatment of iron overload in patients with betathalassemia,requires regular subcutaneous or intravenous infusions. This can lead to reduced quality of life and poor adherence,resulting in increased morbidity and mortality in iron-overloaded patients with beta-thalassemia. Deferasirox (DFX) is an orally administered iron chelator that has been approved for use in many countries. The requirement of an effective,well tolerated iron chelator with a less demanding mode of administration has led to the development of deferasirox. The present study was aimed to compare the satisfaction and compliance with deferoxamine versus deferasirox (Exjade®),a novel oral iron chelator in patients with transfusion - dependent beta- thalassemia. A cross-sectional,single-center investigation study was carried out in the Thalassemia Center of Ibn-Atheer Teaching Hospital in Nineveh province,Iraq. One hundred and eight thalassemic patients aged between 2- 20 years old having received multiple blood transfusions and a serum ferritin greater than 1500 ng/ml. Patients were randomised into two groups. Group 1 received deferoxamine at a dose of 20-50mg/kg/day and group 2 received deferasirox at the dose of 10-30 mg/kg/day. Another 56 apparently healthy volunteers were used as a control group. The assessment of chelation was done during the period between November 2013 and February 2014 by measurement of serum ferritin. Satisfaction and compliance was assessed by using a special questionnaire prepared by the researcher. Out of the 108 thalassemic patients enrolled there was no discontinuation in treatment with the two drugs under study. The serum ferritin did not change significantly in any of the chelation groups. In comparison with the patients who were treated with DFO,those receiving DFX reported a significantly higher rate of compliance and satisfaction (P < 0.05). However,no significant difference was observed between the two groups regarding their satisfaction (P > 0.05).Compliance with deferasirox (50 %) was more than that with deferoxamine (20 %). Satisfaction with deferoxamine was significantly lower than deferasirox (p= 0.00).

Clinical effectiveness of the composition of muramylpeptides from gram-negative bacteria in the treatment of severe chronic generalized periodontitis

2020 ◽  
pp. 24-29
Author(s):  
A.I. Grudyanov ◽  
E.V. Fomenko ◽  
O.V. Kalyuzhin
Keyword(s):  
Clinical Effectiveness ◽  
Main Group ◽  
Control Group ◽  
Gram Negative Bacteria ◽  
Periodontal Pathogens ◽  
Gram Negative ◽  
Periodontal Inflammation ◽  
Clinical Indices ◽  
Periodontal Indices

The effectiveness of the immunomodulator Polymuramil (PM) was determined in the treatment of 40 patients with severe chronic generalized periodontitis based on the dynamics of the values of periodontal indices and the content of periodontal pathogens in the periodontal pockets. Patients of the main group (20 people) were treated with professional hygiene (PGO) in combination with daily intramuscular PM for 5 days at a dose of 200 mcg. Patients of the control group (20 people) were performed only PGO. The effectiveness of treatment was evaluated based on the dynamics of the clinical indices of Muehlemann and PMA and the presence or absence of major periodontal pathogens in the periodontal pockets. Results: in patients of the main group, the phenomena of periodontal inflammation and the main periodontal pathogens were eliminated in a shorter time and to a greater extent in comparison with patients of the control group

scholarly journals A Calorie-Restricted Ketogenic Diet Reduces Cerebral Cortex Vascularization in Prepubertal Rats

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2681
Author(s):  
Viggiano ◽  
Meccariello ◽  
Santoro ◽  
Secondulfo ◽  
Operto ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Substantia Nigra ◽  
Ketogenic Diet ◽  
Capillary Density ◽  
Diet Group ◽  
Cerebral White Matter ◽  
Control Group ◽  
Standard Diet ◽  
Ketogenic Diets ◽  
Prepubertal Rats

The antiepileptic effect of ketogenic diets is acknowledged but its mechanism of action is poorly understood. The present work aimed to evaluate possible effects of a calorie-restricted ketogenic diet (CRKD) on brain growth and angiogenesis in normal prepubertal rats. Two groups of prepubertal rats were fed with a standard diet (group 1) or a CRKD (group 2) for ten weeks. Then, rats were sacrificed and the thickness for the following structures was evaluated by histology: (1) cerebral cortex, (2) deep cerebral white matter, and (3) substantia nigra. The capillary density was also evaluated within: (1) cerebral cortex, (2) dentate gyrus of the hippocampus, (3) periaqueductal grey matter, and (4) substantia nigra. The results showed a smaller thickness of all the areas examined and a reduced capillary density within the cerebral cortex in the CRKD-treated group compared to the control group. These findings suggest an association between reduced angiogenesis within the cerebral cortex and the antiepileptic effects of CRKD.

scholarly journals Effect of a 0.5% chlorhexidine gel on dental plaque superinfecting microorganisms in mentally handicapped patients

2003 ◽  
Vol 17 (3) ◽  
pp. 228-233 ◽  
Author(s):  
Cláudio Mendes Pannuti ◽  
Roberto Fraga Moreira Lotufo ◽  
Silvana Cai ◽  
Maria da Conceição Saraiva ◽  
Nívea Maria de Freitas ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Placebo Group ◽  
Dental Plaque ◽  
Test Group ◽  
Control Group ◽  
Mentally Handicapped ◽  
Bacterial Populations ◽  
Gram Negative ◽  
Supragingival Plaque ◽  
Chlorhexidine Gel

A randomized clinical trial was conducted to investigate the effect of a 0.5% chlorhexidine (CHX) gel on dental plaque superinfecting microorganisms in mentally handicapped patients. Thirty inmates from the institution "Casas André Luiz" were assigned to either test group (CHX gel, n = 15) or control group (placebo gel, n = 15). The gel was administered over a period of 8 weeks. Supragingival plaque samples were collected at baseline, after gel use (8 weeks) and 16 weeks after baseline. The presence of Gram-negative Enterobacteriaceae, Staphylococcus and yeasts was evaluated. No significant growth of any superinfecting microorganism was observed in the CHX group, when compared to the placebo group. The results indicated that the 0.5% chlorhexidine gel did not produce an undesirable shift in these bacterial populations.

scholarly journals Analgesia in newborns: a case-control study of the efficacy of nutritive and non-nutritive sucking stimuli

CoDAS ◽  
2013 ◽  
Vol 25 (4) ◽  
pp. 365-368 ◽  
Author(s):  
Ana Henriques Lima ◽  
Ana Paula Hermont ◽  
Amélia Augusta de Lima Friche
Keyword(s):  
Case Control Study ◽  
Pain Scale ◽  
Case Control ◽  
Control Group ◽  
Pain Response ◽  
The Third ◽  
Nutritive Sucking ◽  
Lower Pain ◽  
Infant Pain ◽  
Control Study

PURPOSE: To verify the nutritive and non-nutritive stimuli efficacy in the newborn's response to pain during venipuncture. METHODS: The main sample was composed of 64 newborns that were randomly divided into three groups. The first group (n=20) received nutritive sucking stimulus that was performed through maternal breastfeeding. The second group (n=21) received non-nutritive sucking stimulus that was performed through the introduction of the researcher little finger in the newborn's oral cavity. The third group or control group (n=23) did not receive any analgesia stimulus. The newborns were evaluated using the Neonatal Infant Pain Scale, and the responses to painful stimuli were compared. RESULTS: The nutritive as well as non-nutritive suction methods provided a comforting effect, resulting in lower pain response scores (p<0.05). There was no difference between the analgesia provided by both methods (p>0.05). CONCLUSION: The nutritive and the non-nutritive sucking stimuli proved to be efficacious tools in relieving pain among newborns.

Cardiac vasculature and flow during pressure-overload hypertrophy

1986 ◽  
Vol 251 (5) ◽  
pp. H1031-H1037 ◽  
Author(s):  
E. A. Breisch ◽  
F. C. White ◽  
L. E. Nimmo ◽  
C. M. Bloor
Keyword(s):  
Blood Flow ◽  
Myocardial Blood Flow ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Capillary Density ◽  
Left Ventricular ◽  
Control Group ◽  
Cross Sectional ◽  
Ventricle Hypertrophy ◽  
Aortic Cuff

The effects of pressure-overload hypertrophy (H) on myocardial blood flow and microvasculature were studied in the porcine left ventricle. Hypertrophy was produced in nine adult pigs by an aortic cuff constriction of the ascending aorta. Eight pigs served as controls. After 30 days the aortic cuff was released, and the hypertrophy group was studied 1 day postrelease. The degree of hypertrophy, determined by left ventricular-to-body weight ratio, was 45%. With hypertrophy, left ventricular blood flows were normal at rest. During exercise with adenosine infusion, myocardial blood flow to the endomyocardium was reduced compared with the control (C) group (H = 4.02 +/- 0.35, P less than 0.05; C = 5.33 +/- 0.41 ml X min-1 X g-1). Minimal coronary vascular resistance in the endomyocardium was increased during exercise with adenosine in the hypertrophy group compared with the control group. Anatomic studies revealed that hypertrophy causes a reduction in the endomyocardial capillary density (H = 1,654 +/- 168, P less than 0.025; C = 2,168 +/- 106, no./mm2) with a similar trend noted for the transmural arteriolar density. Arteriolar media wall cross-sectional area was unaffected by the pressure overload. These results indicate that changes in the vascular bed do not parallel myocyte growth during pressure-overload hypertrophy. The resultant anatomic imbalance compromises endomyocardial flow, making this region vulnerable to ischemia.

scholarly journals Relationships between urinary neural and immune factors in the patients with interstitial cystitis/ bladder painful syndrome

2020 ◽  
Vol 22 (5) ◽  
pp. 879-886
Author(s):  
R. F. Sholan
Keyword(s):  
Mast Cells ◽  
Interstitial Cystitis ◽  
Pearson Correlation ◽  
Control Level ◽  
Clinical Manifestations ◽  
Control Group ◽  
Bladder Tissue ◽  
Bladder Pain ◽  
Group I ◽  
Group Ii

The purpose of this work was to study the relationships between urinary cytokines, mast cells and nerve growth factor (NGF) in the patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Sixty-eight women with clinically diagnosed IC/BPS were under study. Their mean age was 54.2±12.4 years. Urinary concentrations of interleukins (IL-1β, IL-6, IL-8), tumor necrosis factor-α (TNFα), and NGF were determined by ELISA technique. Mast cells were identified in biopsies of mucous membranes from urinary bladder harvested during cystoscopy. Statistical evaluation was performed by Statistica program in Microsoft Excel. Pearson correlation quotients were calculated. Depending on the type of IC/BPS, the patients were divided into 2 groups: group I included 36 patients with classic type of disease; group II comprised 32 patients with non-ulcer type of IC/BPS. No significant differences were revealed between the groups. In 13.9% of patients from group I, the onset of clinical manifestations of the disease was observed at the age of less than 40 years; in group II, 28.1% of the examined mentioned appearance of the disease symptoms at this age. The levels of IL-1β in the patients from group I was 2.4 times higher than in controls (p < 0.05). IL-6, IL-8 and TNFα concentrations exceeded control values by 2.0 (p < 0.05), 2.5 (p < 0.05) and 2.0 times (p < 0.05), respectively. In the patients from group II, the content of IL-1β, IL-6, IL-8 and TNFα was 2.4 (p < 0.05), 2.0 (p < 0.05), 2.0 (p < 0.05) and 1.9 (p < 0.05) times higher than in the control group, respectively. There were no significant differences between groups I and II, in IL-1β, IL-6, and TNFα levels, except of IL-8 in women of group I that was 20.3% higher than in group II. The urinary NGF level in the patients with IC/BPS exceeded the control level 1.6 times (p < 0.05) for group I, and 1.5 times (p < 0.05) for group II. The number of mast cells in the patients of group I was significantly higher than in controls and in group II, i.e., 1.6 (p < 0.05) and 1.4 times (p < 0.05), respectively. In most cases, a direct weak correlation was revealed between the indices. Only in group I, a moderate correlation (r = + 0.508) could be detected between IL-1β and mast cells. Determination of cytokine levels allows to detect activation of inflammatory cells in bladder tissue and provides an opportunity for developing diagnostic strategies. Increased numbers of mast cells may indicate the importance of these cells in the disease progression, whereas elevated levels of NGF in urine suggests that IC/BPS may be caused by chronic inflammation.

scholarly journals THE IMPACT OF COMBINATION OF BREASTFEEDING AND EFFLEURAGE MASSAGE IN REDUCING PAIN RESPONSE IN INFANTS INDUCED BY BLOOD SAMPLING IN C-REACTIVE PROTEIN TEST: AN OBSERVATIONAL CROSS-SECTIONAL STUDY

2018 ◽  
Vol 4 (2) ◽  
pp. 242-248
Author(s):  
Alfi Maziyah ◽  
Diyah Fatmasari ◽  
Desak Made Wenten Parwati ◽  
Rr. Sri Endang Pujiastuti
Keyword(s):  
Intervention Group ◽  
Cross Sectional Study ◽  
Blood Sampling ◽  
Control Group ◽  
Pain Response ◽  
Sectional Study ◽  
C Reactive Protein ◽  
Cross Sectional ◽  
Reactive Protein ◽  
Massage Group

Background: C-reactive protein test is one of clinical assessments to minimize risks of infection in infants. However, its procedure may cause pain. Pain in the infant may result in negative metabolic behavior, physiology and metabolic response. Objective: This study was to describe the infant's pain response by administering a combination of breastfeeding and an effleurage massage on the blood sampling procedure of C-reactive protein examination.         Methods: This was a descriptive observational cross-sectional study. There were 30 infants selected using consecutive sampling technique, which 15 samples assigned in an intervention group (combination of breastfeeding and effleurage massage) and a control group. Premature Infant Pain Profile (PIPP) instrument was used to measure pain. Univariate analysis was performed with the aim to describe data in mean and median.Results: The average of pain response at 1-minute observation in the combination of breastfeeding and effleurage massage group was 7.47 ± 1.356, and the average of pain response in the control group was 10.80 ± 1.897. The average pain at 5-minutes in the intervention group was 3.53 ± 1.922 and control group was 6.00 ± 1.852. Conclusions: Pain responses in the combination of breastfeeding and effleurage massage group were lower than the pain response in the control group.

scholarly journals Leukocyte-Endothelium Interactions during Permanent Focal Cerebral Ischemia in Mice

2004 ◽  
Vol 24 (6) ◽  
pp. 668-676 ◽  
Author(s):  
Hiroharu Kataoka ◽  
Seong-Woong Kim ◽  
Nikolaus Plesnila
Keyword(s):  
Cerebral Ischemia ◽  
Brain Damage ◽  
Molecular Mechanisms ◽  
Focal Cerebral Ischemia ◽  
Fluorescent Microscopy ◽  
Capillary Density ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion ◽  
Adherent Leukocytes

The contribution of leukocyte infiltration to brain damage after permanent focal cerebral ischemia and the underlying molecular mechanisms are still unclear. Therefore, the aim of this study was to establish a mouse model for the visualization of leukocytes in the cerebral microcirculation in vivo and to investigate leukocyte-endothelial interaction (LEI) after permanent middle cerebral artery occlusion (MCAO). Sham-operated 129/Sv mice showed physiologic LEI in pial venules as observed by intravital fluorescent microscopy. Permanent focal cerebral ischemia induced a significant increase of LEI predominantly in pial venules. The number of rolling and adherent leukocytes reached 36.5 ± 13.2/100 μm × min and 22.5 ± 7.9/100 μm × min, respectively at 120 minutes after MCAO ( P = 0.016 vs. control). Of note, rolling and adherent leukocytes were also observed in arterioles of ischemic animals (7.3 ± 3.0/100 μm × min rolling and 3.0 ± 3.6/100 μm × min adherent). Capillary density was not different between groups. These results demonstrate that leukocytes accumulate in the brain not only after transient but also after permanent focal cerebral ischemia and may therefore contribute to brain damage after stroke without reperfusion.

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