Differential Susceptibilities to Azithromycin Treatment of Chlamydial Infection in the Gastrointestinal Tract and Cervix

ABSTRACTEvidence from animal studies suggests that chlamydiae may persist in the gastrointestinal tract (GI) and be a reservoir for reinfection of the genital tract. We hypothesize that there may be a differential susceptibility of organisms in the GI and genital tracts. To determine the effect of azithromycin on persistent chlamydial gut infection, C57BL/6 and BALB/c mice were infected orally and genitally and treated with azithromycin (Az) orally (20, 40, or 80 mg/kg of body weight), and the numbers of chlamydiae were determined from cervix and cecal tissues. The Az concentration in the cecum and cervix was measured by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). Az treatment cleared genital infection in both C57BL/6 and BALB/c mice; however, GI infection was not cleared with the same doses. HPLC data showed the presence of Az at both sites of infection, and significant amounts of Az were measured in treatment groups. However, no significant difference in Az levels between the cecum and the cervix was observed, indicating similar levels of Az reaching both sites of infection. These data indicate that antibiotic levels that are sufficient to cure genital infection are ineffectual against GI infection. The results suggest a reevaluation of antibiotic therapy for chlamydial infection.

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Shufeng Jiedu Capsules Alleviate Lipopolysaccharide-Induced Acute Lung Inflammatory Injury via Activation of GPR18 by Verbenalin

Cellular Physiology and Biochemistry ◽

10.1159/000494184 ◽

2018 ◽

Vol 50 (2) ◽

pp. 629-639 ◽

Cited By ~ 6

Author(s):

Ying Yuan ◽

Qingwu Liao ◽

Mingming Xue ◽

Yujing Shi ◽

Ling Rong ◽

...

Keyword(s):

High Performance ◽

Peritoneal Macrophages ◽

Acute Respiratory Tract Infection ◽

Inflammatory Factors ◽

Mouse Lung ◽

Office Visits ◽

Treatment Groups ◽

Significant Difference ◽

Anti Inflammatory

Background/Aims: Acute respiratory tract infection (ARTI) is the most common reason for outpatient physician office visits. Although powerful and significant in the treatment of infections, antibiotics used for ARTI inappropriately have been an important contributor to antibiotic resistance. We previously reported that Shufeng Jiedu Capsule (SJC) can effectively amplify anti-inflammatory signaling during infection. In this study, we aimed to systematically explore its composition and the mechanism of its effects in ARTI. Methods: Pseudomonas aeruginosa (PAK) strain was used to generate a mouse model of ARTI, which were then treated with different drugs or compounds to determine the corresponding anti-inflammatory roles. High-performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry. was conducted to detect the chemical compounds in SJC. RNAs from the lung tissues of mice were prepared for microarray analysis to reveal globally altered genes and the pathways involved after SJC treatment. Results: SJC significantly inhibited the expression and secretion of inflammatory factors from PAK-induced mouse lung tissues or lipopolysaccharide-induced peritoneal macrophages. Verbenalin, one of the bioactive compounds identified in SJC, also showed notable anti-inflammatory effects. Microarray data revealed numerous differentially expressed genes among the different treatment groups; here, we focused on studying the role of GPR18. We found that the anti-inflammatory role of verbenalin was attenuated in GPR18 knockout mice compared with wild-type mice, although no statistically significant difference was observed in the untreated PAK-induced mice types. Conclusion: Our data not only showed the chemical composition of SJC, but also demonstrated that verbenalin was a significant anti-inflammatory compound, which may function through GPR18.

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A Genital Infection-Attenuated Chlamydia muridarum Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge

mBio ◽

10.1128/mbio.02770-20 ◽

2020 ◽

Vol 11 (6) ◽

Cited By ~ 1

Author(s):

Sandra G. Morrison ◽

Amanda M. Giebel ◽

Evelyn Toh ◽

Arkaprabha Banerjee ◽

David E. Nelson ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Genital Tract ◽

The United States ◽

Effective Vaccine ◽

Genital Infection ◽

Wild Type ◽

Gi Tract ◽

Genital Infections ◽

Content Type ◽

Chlamydia Muridarum

ABSTRACT Chlamydia spp. productively infect mucosal epithelial cells of multiple anatomical sites, including the conjunctiva, lungs, gastrointestinal (GI) tract, and urogenital tract. We, and others, previously established that chlamydial GI tropism is mediated by distinct chromosomal and plasmid factors. In this study, we describe a genital infection-attenuated Chlamydia muridarum mutant (GIAM-1) that is profoundly and specifically attenuated in the murine genital tract. GIAM-1 infected the murine GI tract similarly to wild-type (WT) Chlamydia muridarum but did not productively infect the lower genital tract of female mice, ascend to infect the upper genital tract, or cause hydrosalpinx. However, GI infection of mice with GIAM-1 elicited a transmucosal immune response that protected against subsequent genital challenge with WT Chlamydia muridarum. Collectively, our results demonstrate that chlamydia mutants that are profoundly attenuated for specific organ tissues can be derived and demonstrate that live-attenuated vaccine strains that infect the GI tract, but do not elicit genital tract disease, could be used to protect against chlamydia genital tract infection and disease. IMPORTANCE Chlamydia is the most common sexually transmitted bacterial infection in the United States. Most chlamydia genital infections resolve without serious consequences; however, untreated infection in women can cause pelvic inflammatory disease and infertility. Antibiotics are very effective in treating chlamydia, but most genital infections in both men and women are asymptomatic and go undiagnosed. Therefore, there is a critical need for an effective vaccine. In this work, we show that a mutant chlamydia strain, having substantially reduced virulence for genital infection, colonizes the gastrointestinal tract and produces robust immunity to genital challenge with fully virulent wild-type chlamydia. These results are an important advance in understanding chlamydial virulence and provide compelling evidence that safe and effective live-attenuated chlamydia vaccines may be feasible.

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Subclinical Chlamydial Infection of the Female Mouse Genital Tract Generates a Potent Protective Immune Response: Implications for Development of Live Attenuated Chlamydial Vaccine Strains

Infection and Immunity ◽

10.1128/iai.68.1.192-196.2000 ◽

2000 ◽

Vol 68 (1) ◽

pp. 192-196 ◽

Cited By ~ 22

Author(s):

Hua Su ◽

Ronald Messer ◽

William Whitmire ◽

Scott Hughes ◽

Harlan D. Caldwell

Keyword(s):

Immune Response ◽

Genital Tract ◽

Chlamydial Infection ◽

Transmitted Disease ◽

Female Genital Tract ◽

Indirect Evidence ◽

Protective Immune Response ◽

Genital Infection ◽

Cell Mediated Immunity ◽

Female Genital

ABSTRACT Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) for which a vaccine is needed. CD4+ T-helper type 1 (Th1) cell-mediated immunity is an important component of protective immunity against murine chlamydial genital infection. Conventional vaccine approaches have not proven effective in eliciting chlamydial-specific CD4 Th1 immunity at the genital mucosa. Thus, it is possible that the development of a highly efficacious vaccine against genital infection will depend on the generation of a live attenuated C. trachomatis vaccine. Attenuated strains of C. trachomatis do not exist, so their potential utility as vaccines cannot be tested in animal models of infection. We have developed a surrogate model to study the effect of chlamydial attenuation on infection and immunity of the female genital tract by treating mice with a subchlamydiacidal concentration of oxytetracycline following vaginal infection. Compared to untreated control mice, antibiotic-treated mice shed significantly fewer infectious organisms (3 log10) from the cervico-vagina, produced a minimal inflammatory response in urogenital tissue, and did not experience infection-related sequelae. Antibiotic-treated mice generated levels of chlamydia-specific antibody and cell-mediated immunity equivalent to those of control mice. Importantly, antibiotic-treated mice were found to be as immune as control untreated mice when rechallenged vaginally. These findings demonstrate that subclinical chlamydial infection of the murine female genital tract is sufficient to stimulate a potent protective immune response. They also present indirect evidence supporting the possible use of live attenuated chlamydial organisms in the development of vaccines against chlamydial STDs.

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Relevance Predictability in Information Retrieval Systems

Methods of Information in Medicine ◽

10.1055/s-0038-1636254 ◽

1967 ◽

Vol 06 (02) ◽

pp. 45-51 ◽

Cited By ~ 6

Author(s):

A. Kent ◽

J. Belzer ◽

M. Kuhfeerst ◽

E. D. Dym ◽

D. L. Shirey ◽

...

Keyword(s):

Information Retrieval ◽

Experimental Conditions ◽

Treatment Groups ◽

Retrieval Systems ◽

Significant Difference ◽

Information Retrieval Systems ◽

High Predictability ◽

Intermediate Response ◽

Quantitative Indicators ◽

Level Of Processing

An experiment is described which attempts to derive quantitative indicators regarding the potential relevance predictability of the intermediate stimuli used to represent documents in information retrieval systems. In effect, since the decision to peruse an entire document is often predicated upon the examination of one »level of processing« of the document (e.g., the citation and/or abstract), it became interesting to analyze the properties of what constitutes »relevance«. However, prior to such an analysis, an even more elementary step had to be made, namely, to determine what portions of a document should be examined.An evaluation of the ability of intermediate response products (IRPs), functioning as cues to the information content of full documents, to predict the relevance determination that would be subsequently made on these documents by motivated users of information retrieval systems, was made under controlled experimental conditions. The hypothesis that there might be other intermediate response products (selected extracts from the document, i.e., first paragraph, last paragraph, and the combination of first and last paragraph), that would be as representative of the full document as the traditional IRPs (citation and abstract) was tested systematically. The results showed that:1. there is no significant difference among the several IRP treatment groups on the number of cue evaluations of relevancy which match the subsequent user relevancy decision on the document;2. first and last paragraph combinations have consistently predicted relevancy to a higher degree than the other IRPs;3. abstracts were undistinguished as predictors; and4. the apparent high predictability rating for citations was not substantive.Some of these results are quite different than would be expected from previous work with unmotivated subjects.

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Effect of Fixed Minidose Warfarin, Conventional Dose Warfarin and Aspirin on INR and Prothrombin Fragment 1 + 2 in Patients with Atrial Fibrillation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656065 ◽

1997 ◽

Vol 77 (05) ◽

pp. 0845-0848 ◽

Cited By ~ 23

Author(s):

B G Koefoed ◽

C Feddersen ◽

A L Gulløv ◽

P Petersen

Keyword(s):

Atrial Fibrillation ◽

International Normalized Ratio ◽

Coagulation System ◽

Nonvalvular Atrial Fibrillation ◽

Treatment Groups ◽

Prothrombin Fragment ◽

Conventional Dose ◽

Dose Warfarin ◽

Significant Difference ◽

Changes Over Time

SummaryThe efficacy of conventional dose adjusted oral anticoagulation for stroke prevention in patients with non-valvular atrial fibrillation is well- documented but not considered ideal as primary antithrombotic treatment in elderly patients. The antithrombotic effect of fixed minidose warfarin 1.25 mg/day alone or in combination with aspirin 300 mg/day, of conventional dose adjusted warfarin (INR 2.0-3.0), and of aspirin 300 mg/day have been investigated in outpatients with chronic nonvalvular atrial fibrillation in the second Copenhagen Atrial Fibrillation, Aspirin and Anticoagulant Therapy Study (AFASAK 2). In order to investigate the effect on the coagulation system of the treatments, the International Normalized Ratio of the prothrombin time (INR) and prothrombin fragment 1 + 2 (F1 +2) were monitored at baseline and after three months of treatment in 100 patients consecutively included in the trial. At baseline no differences in INR and F1+2 between the four treatment groups were present. After three months of therapy the level of INR increased significantly from baseline in patients receiving warfarin in any dose and the level of F1+2 decreased significantly by combined minidose warfarin-aspirin and by dose adjusted warfarin. When comparing the changes over time in FI +2 (three-month value minus baseline value) during therapy with fixed minidose warfarin, combined minidose warfarin-aspirin and aspirin alone no significant difference between the groups was found. In conclusion, INR was changed by all three warfarin regimens but only dose adjusted warfarin (INR 2.0-3.0) had a marked effect on F1+2.

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Association of biological antirheumatic therapy with risk for type 2 diabetes: a retrospective cohort study in incident rheumatoid arthritis

BMJ Open ◽

10.1136/bmjopen-2020-042246 ◽

2021 ◽

Vol 11 (6) ◽

pp. e042246

Author(s):

Sanjoy K Paul ◽

Olga Montvida ◽

Jennie H Best ◽

Sara Gale ◽

Attila Pethö-Schramm ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Type 2 Diabetes ◽

T Cell ◽

Disease Modifying Antirheumatic Drugs ◽

Antirheumatic Therapy ◽

Treatment Groups ◽

Significant Difference ◽

Necrosis Factor

ObjectiveTo explore possible associations of treatment with biological disease-modifying antirheumatic drugs (bDMARDs), including T-cell-based and interleukin-6 inhibition (IL-6i)-based therapies, and the risk for type 2 diabetes mellitus (T2DM) in patients with rheumatoid arthritis (RA).Study design, setting and participantsFive treatment groups were selected from a United States Electronic Medical Records database of 283 756 patients with RA (mean follow-up, 5 years): never received bDMARD (No bDMARD, n=125 337), tumour necrosis factor inhibitors (TNFi, n=34 873), IL-6i (n=1884), T-cell inhibitors (n=5935) and IL-6i+T cell inhibitor abatacept (n=1213). Probability and risk for T2DM were estimated with adjustment for relevant confounders.ResultsIn the cohort of 169 242 patients with a mean 4.5 years of follow-up and a mean 641 200 person years of follow-up, the adjusted probability of developing T2DM was significantly lower in the IL-6i (probability, 1%; 95% CI 0.6 to 2.0), T-cell inhibitor (probability, 3%; 95% CI 2.3 to 3.3) and IL-6i+T cell inhibitor (probability, 2%; 95% CI 0.1 to 2.9) groups than in the No bDMARD (probability, 5%; 95% CI 4.6 to 4.9) and TNFi (probability, 4%; 95% CI 3.7 to 4.7) groups. Compared with No bDMARD, the IL-6i and IL-6i+T cell inhibitor groups had 37% (95% CI of HR 0.42 to 0.96) and 34% (95% CI of HR 0.46 to 0.93) significantly lower risk for T2DM, respectively; there was no significant difference in risk in the TNFi (HR 0.99; 95% CI 0.93 to 1.06) and T-cell inhibitor (HR 0.96; 95% CI 0.82 to 1.12) groups.ConclusionsTreatment with IL-6i, with or without T-cell inhibitors, was associated with reduced risk for T2DM compared with TNFi or No bDMARDs; a less pronounced association was observed for the T-cell inhibitor abatacept.

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Capsular closure versus unrepaired interportal capsulotomy after hip arthroscopy in patients with femoroacetabular impingement, results of a patient-blinded randomised controlled trial

Hip International ◽

10.1177/11207000211005762 ◽

2021 ◽

pp. 112070002110057

Author(s):

Niels H Bech ◽

Inger N Sierevelt ◽

Sheryl de Waard ◽

Boudijn S H Joling ◽

Gino M M J Kerkhoffs ◽

...

Keyword(s):

Randomised Controlled Trial ◽

Femoroacetabular Impingement ◽

Hip Arthroscopy ◽

Controlled Trial ◽

Poor Quality ◽

Control Group ◽

Treatment Groups ◽

Significant Difference ◽

Randomised Controlled

Background: Hip capsular management after hip arthroscopy remains a topic of debate. Most available current literature is of poor quality and are retrospective or cohort studies. As of today, no clear consensus exists on capsular management after hip arthroscopy. Purpose: To evaluate the effect of routine capsular closure versus unrepaired capsulotomy after interportal capsulotomy measured with NRS pain and the Copenhagen Hip and Groin Outcome Score (HAGOS). Materials and methods: All eligible patients with femoroacetabular impingement who opt for hip arthroscopy ( n = 116) were randomly assigned to one of both treatment groups and were operated by a single surgeon. Postoperative pain was measured with the NRS score weekly the first 12 weeks after surgery. The HAGOS questionnaire was measured at 12 and 52 weeks postoperatively. Results: Baseline characteristics and operation details were comparable between treatment groups. Regarding the NRS pain no significant difference was found between groups at any point the first 12 weeks after surgery ( p = 0.67). Both groups significantly improved after surgery ( p < 0.001). After 3 months follow-up there were no differences between groups for the HAGOS questionnaire except for the domain sport ( p = 0.02) in favour of the control group. After 12 months follow-up there were no differences between both treatment groups on all HAGOS domains ( p > 0.05). Conclusions: The results of this randomised controlled trial show highest possible evidence that there is no reason for routinely capsular closure after interportal capsulotomy at the end of hip arthroscopy. Trial Registration: This trial was registered at the CCMO Dutch Trial Register: NL55669.048.15.

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Metabolomic analysis reveals the interaction of primary and secondary metabolism in white, pale green, and green pak choi (Brassica rapa subsp. chinensis)

Applied Biological Chemistry ◽

10.1186/s13765-020-00574-2 ◽

2021 ◽

Vol 64 (1) ◽

Author(s):

Hyeon Ji Yeo ◽

Seung-A Baek ◽

Ramaraj Sathasivam ◽

Jae Kwang Kim ◽

Sang Un Park

Keyword(s):

Secondary Metabolites ◽

Brassica Rapa ◽

High Performance ◽

Reducing Power ◽

Total Phenolic ◽

Pak Choi ◽

Primary And Secondary Metabolites ◽

Chlorophyll Contents ◽

Significant Difference ◽

Pale Green

AbstractThis study aimed to comprehensively analyze primary and secondary metabolites of three different-colored (white, pale green, and green) pak choi cultivars (Brassica rapa subsp. chinensis) using gas chromatography attached with time-of-flight mass spectrometry (GC-TOFMS) and high-performance liquid chromatography (HPLC). In total, 53 primary metabolites were identified and subjected to partial least-squares discriminant analysis. The result revealed a significant difference in the primary and secondary metabolites between the three pak choi cultivars. In addition, 49 hydrophilic metabolites were detected in different cultivars. Total phenolic and glucosinolate contents were highest in the pale green and green cultivars, respectively, whereas total carotenoid and chlorophyll contents were highest in the white cultivar. Superoxide dismutase activity, 2,2-diphenyl-1-picrylhydraz scavenging, and reducing power were slightly increased in the white, pale green, and green cultivars, respectively. In addition, a negative correlation between pigments and phenylpropanoids was discovered by metabolite correlation analysis. This approach will provide useful information for the development of strategies to enhance the biosynthesis of phenolics, glucosinolates, carotenoids, and chlorophyll, and to improve antioxidant activity in pak choi cultivars. In addition, this study supports the use of HPLC and GC-TOFMS-based metabolite profiling to explore differences in pak choi cultivars.

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SUBCHRONIC TOXICITY TEST OF COMBINATION ETHANOL EXTRACT OF DETAM 1 SOYBEAN (GLYCINE MAX L. MERR) AND JATI BELANDA (GUAZUMA ULMIFOLIA LAMK) TOWARD FUNCTION, WEIGHT, AND HISTOPATHOLOGICAL OF WISTAR RAT LIVER

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2016.v9i5.13237 ◽

2016 ◽

Vol 9 (5) ◽

pp. 197

Author(s):

Meilinah Hidayat ◽

Sijani Prahastuti ◽

Estherolita Dewi ◽

Dewi Safitri ◽

Siti Farah Rahmawati ◽

...

Keyword(s):

Liver Function ◽

Toxicity Test ◽

Low Dose ◽

Ethanol Extract ◽

Good Effect ◽

Control Group ◽

High Dose ◽

Subchronic Toxicity ◽

Treatment Groups ◽

Significant Difference

ABSTRACTObjective: As an antiobesity therapy, combination extracts of Detam 1 soybean and Jati Belanda will be consumed for a long time; therefore, theirtoxicities to the liver need to be investigated. To determine the effect of subchronic toxicity test of combination of ethanol extract of Detam 1 soybean(EEDS) and ethanol extract of Jati Belanda (EEJB) on liver function with parameters: Alanine transaminase (ALT), macroscopic, and histopathologicalof liver.Methods: This study was conducted on 120 Wistar rats (60 males and 60 females), 90 days (treatment group) and 120 days (satellite group). Ratswere divided into six treatment groups (3 test materials, 1 control, and 2 satellites); each group included 10 males and 10 females.Results: ALT levels of treatment groups (low dose, medium, and high), both males and females were lower than the control group (p<0.05). Thetreatment groups demonstrated a good effects effect on liver function. Liver weight of all groups showed no significant difference compared with thecontrol group (p>0.05). Results of histopathological score interpretation of male and female liver rats of low dose groups were not disturbed; middledose groups were slightly disturbed and high dose groups were damaged. Satellite high doses of male groups were disrupted, while female groupswere not.Conclusion: The combination of EEDS and EEJB has a good effect on liver function, did not lead to change organ weight and at low doses did not causerenal histopathology damage in rats after 90 days administration.Keywords: Combination of soybean Jati Belanda, Toxicity subchronic test, Function, Weight, Histopathology, Liver.

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Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: results of a 4-year multicenter randomized study.

Journal of Clinical Oncology ◽

10.1200/jco.1988.6.9.1401 ◽

1988 ◽

Vol 6 (9) ◽

pp. 1401-1410 ◽

Cited By ~ 207

Author(s):

A Rossi ◽

R Molinari ◽

P Boracchi ◽

M Del Vecchio ◽

E Marubini ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Randomized Study ◽

Nasopharyngeal Cancer ◽

Distant Metastases ◽

Undifferentiated Carcinoma ◽

Treatment Groups ◽

Distant Failure ◽

Curative Radiotherapy ◽

Significant Difference ◽

Base Of The Skull

To evaluate the effect of adjuvant chemotherapy in patients with local-regional nasopharyngeal carcinoma (NPC) (squamous or undifferentiated) in complete remission at the end of curative radiotherapy (RT) 229 patients were randomized from 1979 to 1983 in a multicenter study to no further therapy (116 patients) or a combination of vincristine, cyclophosphamide, and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) (VCA) for six monthly cycles (113 patients). The RT and RT + VCA groups were well balanced for median age (50 v 49 years), histology (undifferentiated carcinoma, 73% v 70%), tumor extent (tumor limited to nasopharynx, 57% v 57%), and nodal extent (negative nodes 26% v 24%, nodes in the lower cervical levels, 17% v 16%). RT was delivered to the nasopharynx, the base of the skull, and bilateral cervical nodes using a split course technique over 10 weeks up to the dose of 60 to 70 Gy in involved sites and 50 Gy to negative nodes. Response to RT was evaluated within 65 days post-RT treatment. Analysis at 48 months did not show significant difference between the two treatment groups in terms of relapse-free survival (RT, 55.8%, RT + VCA, 57.7%, P = .45) and overall survival (RT, 67.3%, RT + VCA, 58.5%, P = .13). The pattern of relapse was similar in the two treatment arms. Distant metastases were the cause of treatment failure in about 50% of relapsing patients. Although the results of the present study did not show any benefit from VCA administered after curative RT, combined systemic chemotherapy should be further explored due to the high incidence of local and distant failure after intensive RT.

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