The pivotal role played by lipocalin-2 in chronic inflammatory pain

Jha, M.K.,Jeon, S.,Jin, M.,Ock, J.,Kim, J.H.,Lee, W.H.,Suk, K. Academic Press 2014 Experimental neurology Vol.254 No.-

Lipocalin-2 (LCN2) is an acute phase protein induced in response to injury, infection or other inflammatory stimuli. Based on the previously reported involvement of LCN2 in chemokine induction and in the recruitment of neutrophils at the sites of infection or tissue injury, we investigated the role of LCN2 in the pathogenesis of chronic/persistent inflammatory pain hypersensitivity. In the complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model, LCN2 expression was strongly induced in the ipsilateral hindpaws, peaking at 12h after CFA injection and then gradually subsiding. In CFA-injected hindpaw tissues, LCN2 and its receptor 24p3R were mainly expressed in infiltrating neutrophils and macrophages. CFA-induced thermal hyperalgesia and mechanical allodynia were significantly diminished in Lcn2-deficient mice compared to wild-type animals. Furthermore, neutrophil infiltration, myeloperoxidase activity, expression of TNF-α, IL-1β and MIP-2 in CFA-injected hindpaws, and spinal glial activation were markedly reduced by Lcn2 deficiency. An intraplantar injection of recombinant LCN2 protein induced thermal and mechanical hypersensitivities in naive mice, and this was accompanied by neutrophil and macrophage infiltration into the hindpaws and glial activation in the dorsal horn of the spinal cord. Taken together, our results show that inflammatory cell-derived LCN2 at the sites of inflammation plays important roles in central sensitization and the subsequent nociceptive behavior in the rodent model of chronic inflammatory pain.

The Standardized Extract of <i>Limonium tetragonum</i> Alleviates Chronic Alcoholic Liver Injury in C57Bl/6J Mice

Kim, Na-Hyun,Heo, Jeong-Doo,Rho, Jung-Rae,Yang, Min Hye,Jeong, Eun Ju Medknow PublicationsMedia Pvt Ltd 2018 Pharmacognosy magazine Vol.14 No.53

<P><B>Background:</B></P><P>In traditional folk medicine, <I>Limonium tetragonum</I> is used in the treatment of uterine hemorrhage, tinnitus, and oligomenorrhea.</P><P><B>Objective:</B></P><P>This study aimed to identify the therapeutic effect of <I>L. tetragonum</I> EtOAc extract (EALT) on liver of mice with chronic alcohol poisoning.</P><P><B>Materials and Methods:</B></P><P>C57BL/6J mice were administered 100 mg/kg of EALT with a single binge ethanol/Lieber-DeCarli liquid diet for 8 weeks.</P><P><B>Results:</B></P><P>The chronic-binge ethanol diet induced a significant increase in liver marker enzyme activities. Coadministration of EALT reversed the elevation of serum total cholesterol and triglyceride as well as aspartate aminotransferase and alanine aminotransferase due to chronic alcohol consumption. Histologic findings including markedly attenuated fat accumulation in hepatocytes were observed in EALT-treated mice. EALT supplementation prevented alcoholic liver injury through attenuation of inflammatory mediators such as toll-like receptor-4, cytochrome P4502E1, and cyclooxygenase-2, and inflammatory cytokine interleukin-6.</P><P><B>Conclusion:</B></P><P>Results provided direct experimental evidence for the hepatoprotective effect of EALT in the NIAAA mouse model. Therapeutic attempts with the <I>L. tetragonum</I> extract might be useful in the management of alcoholic liver disease.</P><P><B>SUMMARY</B></P><P><P>Halophyte <I>Limonium tetragonum</I> has recently been of interest in Korea for its nutritional value and salty taste which made it an ideal vegetable</P><P>Phytochemical analysis of <I>L. tetragonum</I> EtOAc extract (EALT) resulted in nine compounds including catechins and myricetin glycosides as main components</P><P>Administration of EALT for 8 weeks showed hepatoprotective effect on Lieber-DeCarli diet-fed mouse model</P><P>A significant decrease in liver marker enzymes and inflammatory mediators was also detected.</P></P> >[FIG OMISSION]</BR><P><B>Abbreviations used:</B> EALT: <I>L. tetragonum</I> EtOAc extract; TC: Total cholesterol; TG: Triglyceride; ROS: Reactive oxygen species; CYP2E1: Cytochrome P4502E1; TLR-4: Toll-like receptor-4; COX-2: Cyclooxygenase-2.</P>

만성 피부 염증소견을 보인 개의 면역학적 특성 분석 연구

조선주,고민수,정복기,고재형,한동운,이봉주,윤소라 한국임상수의학회 2009 한국임상수의학회지 Vol.26 No.5

High levels of inflammatory cytokines were proposed contributors to the pathogenesis of a various inflammatory skin disorders. Therefore, investigating the immune response of the inflammatory skin disorder allows a better understanding of pathogenesis of a various inflammatory skin disorders and therapeutic approaches. The aim of this study was to analyze of the immune response in dogs with chronic inflammatory skin disease. To this aim, the present study evaluated relative mRNA expression of canine IFN-γ, IL-4, TGF-β‚ and IL-10 using TaqMan realtime PCR assays and semi-quantitative RT-PCR in freshly isolated peripheral blood mononuclear cells from twenty dogs with chronic inflammatory skin disease and ten normal dogs. The relative mRNA expression levels of IL-4 mRNA were significantly higher in dogs with chronic inflammatory skin disease than those in normal dogs (P < 0.01). The results of present study also showed a tendency towards increased expression of IL-10 transcripts in dogs with chronic inflammatory skin disease. However, there were no significant differences in the levels IFN-γ, TGF-β‚ between normal and chronically inflammed dogs. In addition, the concentration of serum IgE was significantly increased in dogs with chronic inflammatory skin disease compared with those in normal dogs (P < 0.01). In histopathological examination, we found that there were markedly increased mast cell counts in chronically inflammed dogs (P < 0.05). These results suggest that the pathogenesis of chronic inflammatory skin disease might be associated with a T-cell mediated inflammatory responses characterized by a Th2-skewed immune response. Based on these results, the modulation of Th1/Th2 balance may be an effective therapeutic strategy for the treatment of chronic inflammatory skin disease.

연교(連翹)가 만성 비세균성 전립선영 Rat의 염증발현인자 및 세포조직 변화에 미치는 영향

이진신,안영민,안세영,두호경,이병철,Lee, Jin-Sin,Ahn, Young-Min,Ahn, Se-Young,Doo, Ho-Kyung,Lee, Byung-Cheol 대한한방내과학회 2006 大韓韓方內科學會誌 Vol.27 No.3

Objective : The etiology of chronic prostatitis is likely multifactorial, resulting from either a cascade of events after an initiating factor or from a variety of etiologic mechanisms. There is substantiating evidence to support the role of the inflammatory responses in its pathogenesis, and the clinical value in the evaluation of therapeutic efficacy. Forsythiae Frucus has been traditionally used in treatment of inflammatory diseases, including of prostatitis and urinary tract inflammation. In this study, we investigated the effects of Forsythiae Frucus on inflammatory cytokines and cyto-pathological alternation in the rat model of chronic non-bacterial prostatitis induced by castration and $17{\beta}$-estradiol treatment. Methods : Two-month-old rats were treated with $17{\beta}$-estradiol after castration for induction of experimental non-bacterial prostatitis. which is similar to human chronic prostatitis in histopathological profiles. Forsythiae Frucus as an experimental specimen, and testosterone as a positive control, were administered orally. The prostates were evaluated by histopathologlcal parameters including the epithelial score and epithelio-stromal ratio for glandular damage. and the expression of inflammatory cytokine genes including interleukin (IL)-$1{\beta}$, IL-5, IL-12, tumor necrosis factor (TNF)-$\alpha$. eotaxin, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2(cox-2). Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation. the rats treated with Forsythiae Frucus showed a diminished range of tissue damage. Epithelial score was improved in the Forsythiae Frucus group over that of the control (P<0.05). The epithelia-stromal ratio was lower in the Forsythiae Frucus group when compared to that of the control (P<0.05). In the reverse transcription-polymerase chain reaction (RT-PCR) of inflammatory cytosine genes. Forsythiae Frucus inhibited the expression of IL-$1{\beta}$, TNF-$\alpha$, iNOS, cox-2 genes, while it modulated the expression of IL-5, which is an anti-inflammatory cytokine. Conclusions : These findings suggest that Forsythiae Frucus may protect the glandular epithelial cells and also inhibit stromal proliferation in association with the immune modulation including the suppression of inflammatory cytokines and increase of anti-inflammatory cytokines. From theses results. we suggest that Forsythiae Frucus could be a useful remedy agents for treating chronic non-bacterial prostatitis.

Involvement of the cannabinoid system in chronic inflammatory intestinal diseases: opportunities for new therapies

Priscila A. Lima,Bárbara B. Berg,Marina Gomes Miranda e Castor 대한장연구학회 2022 Intestinal Research Vol.20 No.4

The components of the endogenous cannabinoid system are widely expressed in the gastrointestinal tract contributing to local homeostasis. In general, cannabinoids exert inhibitory actions in the gastrointestinal tract, inducing anti-inflammatory, antiemetic, antisecretory, and antiproliferative effects. Therefore, cannabinoids are interesting pharmacological compounds for the treatment of several acute intestinal disorders, such as dysmotility, emesis, and abdominal pain. Likewise, the role of cannabinoids in the treatment of chronic intestinal diseases, such as irritable bowel syndrome and inflammatory bowel disease, is also under investigation. Patients with chronic intestinal inflammatory diseases present impaired quality of life, and mental health issues are commonly associated with long-term chronic diseases. The complex pathophysiology of these diseases contributes to difficulties in diagnosis and, therefore, in the choice of a satisfactory treatment. Thus, this article reviews the involvement of the cannabinoid system in chronic inflammatory diseases that affect the gastrointestinal tract and highlights possible therapeutic approaches related to the use of cannabinoids.

만성 부비동염과 비침습형 진균성 부비동염에서 상악동 점막에 침윤된 엽증세포의 정량적 비교

윤두환,정유삼,이봉재 대한이비인후과학회 2001 대한이비인후과학회지 두경부외과학 Vol.44 No.1

십이지장 궤양 환자와 만성 위염 환자의 염증 분포의 차이 및 H. pylori 집락도와 염증도의 상관관계

유광하,진춘조,박형석,이재동,김예리,윤성욱,이수인,윤호상 건국대학교 의과학연구소 1998 건국의과학학술지 Vol.- No.8

Are pulmonary hemostasis and fibrinolysis out of balance in equine chronic pneumopathies?

Ann Kristin Barton,Caroline Wirth,Angelika Bondzio,Ralf Einspanier,Heidrun Gehlen 대한수의학회 2017 Journal of Veterinary Science Vol.18 No.3

Clinical examination, bronchoalveolar lavage fluid (BALF) cytology, acute-phase protein, and pulmonary hemostasis and fibrinolysis marker (fibrinogen, serum amyloid A [SAA], and D-dimer) results were compared between control and respiratory disease-affected horses. Using a clinical scoring system, horses (n = 58) were classified as respiratory disease-free (Controls, n = 15) or with recurrent airway obstruction (RAO; n = 18), inflammatory airway disease (n = 14) or chronic interstitial pneumopathy (n = 11). There were no significant differences in fibrinogen concentrations among groups, but there was a trend toward a lower value in controls (median 0.0024 g/L) than in horses with chronic pneumopathies (median 0.0052 g/L), in particular, those with RAO (median 0.0062 g/L). Fibrinogen concentration was positively correlated with percentage of neutrophils in BALF (rs = 0.377, p = 0.004). SAA concentrations were low; 65.5% of samples were below the detection limit. D-dimer concentrations were also low and quantifiable concentrations were only obtained after ultrafiltration and only in RAO (median 0.1 mg/L). In conclusion, there was limited evidence of increased coagulatory activity in chronic pneumopathies, apart from RAO. It is uncertain whether fibrinogen and D-dimer concentrations increased due to their role as acute-phase proteins or as a misbalance of coagulation and fibrinolysis.

만성요통의 치료에 있어서 Lonazolac-Ca(Irritren^(�))과 Naproxen의 임상적 효과에 대한 비교연구

장웅규,전상룡,김현집 한국병원약사회 1997 병원약사회지 Vol.14 No.3

Chronic low back pain is a high-profile symptom in industrialized societies. To control chronic low back pain nonsteroidal anti-inflammatory drugs have been used so easily and widely. We investigated clinical effectiveness of a newly developed NSAID, Lonazolac-Ca(Irritren^(R)), and compared it to naproxen which has been used so long. We recommanded 50 chronic low back pain patients to take lrritren and Naproxen with double blind method. The patients have suffered from low back pain for more than 3 months and were not included in surgical indication. Irritren group was 27 patients and Naproxen group 23 patients. There was no significant statistical difference in age, symptom duration, and pre-medication functional status (ROM degree) between two drug groups. Total medication period was 33months(aberage 1.4 months). Back pain has much more improved in Irritren group (59%, 16 out of 27) than Naproxen group (35%, 8 out of 23), but statistically not significant. And degree of functional improvement also seemed to be larger in Irritren group than Naproxen group with Rom assessment (P=0.045). 10% of the patients showed gastrointestinal symptoms and hypersensitivity reaction but other serious side effects were not observed. So we concluded that these two drugs are useful and safe in the control of chronic low back pain.

Chronic inflammatory demyelinating polyradiculoneuropathy in children: characterized by subacute, predominantly motor dominant polyeuropathy with a favorable response to the treatment

Jo, H. Y.,Park, M.-G.,Kim, D.-S.,Nam, S.-O.,Park, K.-H. Blackwell Publishing Ltd 2010 Acta neurologica Scandinavica Vol.121 No.5

<P>Jo HY, Park M-G, Kim D-S, Nam S-O, Park K-H. Chronic inflammatory demyelinating polyradiculoneuropathy in children: characterized by subacute, predominantly motor dominant polyeuropathy with a favorable response to the treatment.Acta Neurol Scand: 2010: 121: 342–347.© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard.</P><P>Objectives – </P><P>Chronic inflammatory demyelinating polyradiculopathy (CIDP) is less well-studied in children than in adults, probably due to its relative rarity. This study was performed in order to characterize the clinical features of CIDP in children.</P><P>Materials and methods – </P><P>Twenty-eight patients with CIDP who were followed up for more than 1 year were included, and were divided into a child (<I>n</I> = 7, age <16) and an adult group (<I>n</I> = 21, age ≥16). Then, we have assessed the initial progression pattern, clinical course, and serial nerve conduction findings in each patient. Finally, differential features in child and adult group were analyzed.</P><P>Results – </P><P>Distinguishing features in the child group include subacute progression within less than 2 months, predominant motor system involvement in lower extremities, and marked improvement in response to immune modulating therapy. Our study also suggested that serial nerve conduction study may be useful in assessing the effectiveness of the treatment in children. </P><P>Conclusions – </P><P>Our study showed that children with CIDP have some distinguishing features from adults in terms of clinical course and response to treatment.</P>