Effects of a novel curcumin derivative on the functions of kidney in streptozotocin-induced type 2 diabetic rats

Abstract

Objective

B6, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aimed to explore the efficacy of B6 on diabetic nephropathy and the related mechanisms.

Materials and methods

The effects of B6 were studied on fast-blood glucose, serum creatinine, urea nitrogen, urine albumen/24 h, pathological changes of main organs, the levels of ACE2 and ACE2 mRNA in the rat model of diabetes induced by streptozotocin.

Results

The results showed that B6 treatment could reduce serum creatinine, urea nitrogen, urine albumen/24 h, decrease the level of AngII, improve the renal pathological changes in diabetic rats and increase the levels of ACE2 and ACE2 mRNA.

Conclusion

These results suggested B6 could protect the renal function of diabetic rats. This study provided scientific basis for the further researches and clinical applications of B6.

Interferon-β inhibits inflammatory responses mediators via suppression of iNOS signaling pathway in PBMCs from patients with primary Sjögren’s syndrome

Abstract

Background

Primary Sjögren's syndrome (pSS) represents a chronic, systemic autoimmune disorder, characterized by lymphocytic infiltration of exocrine glands, inducing compromised secretory function and tissue destruction. Increasing evidence had revealed that inflammatory mediators, such as nitric oxide (NO) and pro-inflammatory cytokines, are critical in the development and perpetuation of pSS systemic manifestations. In our current study, we aimed to investigate the ex vivo immunomodulatory effect of interferon (IFN)-β on iNOS expression, as well as on pro-inflammatory (tumor necrosis factor (TNF)-α, interleukin (IL)-6) and immunoregulatory (IL-10) cytokine production. Furthermore, we examined potential associations between the influence of IFN-β treatment on NO production, and pSS clinical and serological manifestations.

Methods

In 41 pSS patients documented for their clinical and serological features, NO and cytokines levels were measured by the Griess method and enzyme-linked immunosorbent assay, respectively. Inducible nitric oxide synthase expression was analyzed by fluorescence immunostaining assay, using peripheral blood mononuclear cells (PBMCs) isolated from healthy controls and pSS patients.

Results

Our results revealed a strong down-modulating effect of IFN-β in the secretion of pro-inflammatory mediators including TNF-α, IL-6, and NO production. Interestingly, IFN-β exerts an increase in IL-10 levels. The most suppressive effect exerted by IFN-β on NO production was importantly reported for patients with neurological manifestation. This immunomodulatory effect of IFN-β on NO production is highly related to the decrease of inducible nitric oxide synthase (iNOS) expression.

Conclusion

Our findings highlight a consistent ex vivo inhibitory effect of IFN-β on pro-inflammatory cytokine production and NO pathway in pSS patients. Our data suggest that IFN-β could represent a potential candidate for targeting inflammation during pSS.

Influence of disease-modifying antirheumatic drugs on oxidative and nitrosative stress in patients with rheumatoid arthritis

Abstract

Background

Nitro-oxidative stress plays a central role in the pathogenesis of rheumatoid arthritis (RA) and several articles show correlation with disease activity. However, the influence and mechanisms by which disease-modifying antirheumatic drugs (DMARDs) may interfere with nitro-oxidative stress are poorly understood.

Objective

To show the available data on the effect of the DMARDs on the nitro-oxidative stress in RA patients.

Methods

A bibliographic search was carried out in the electronic databases PUBMED, Lilacs, Scientific Electronic Library Online (SCIELO), and Science Direct and the research was limited to human studies, independently of the publication date.

Results

Most studies were performed with infliximab (IFX, 4 articles), tocilizumab (TCZ, 3 articles) and methotrexate (MTX, 2 articles). MTX and leflunomide showed similar results with reduction of nitric oxide. The studies with TCZ verified a marked decrease of reactive oxygen and nitrogen species. Most studies with IFX found a reduction of protein oxidation, evaluated by protein carbonyl measurement. In the present review, the most remarkable results were observed with the increase of the antioxidant defenses through several markers and antioxidant systems. The only study with etanercept showed very similar results to those obtained with MTX, with decreased pentosidine and oxidative DNA damage.

Conclusions

The majority of the studies reported in this work showed an improvement in the redox state, which could be related to success of the therapy. Thus, oxidative and nitrosative stress markers may be useful to early evaluate the response of DMARDs in patients with RA.

Neuropsychiatric clinical manifestations in elderly patients treated with hydroxychloroquine: a review article

Abstract

Little is known about the development of psychosis during hydroxychloroquine (HCQ) treatment, especially in elderly patients affected by rheumatic diseases, with multiple comorbidities and treatments. To summarize the available evidence on HCQ-induced psychosis in elders, we performed a literature review. Additionally, individual case safety reports sent to the European Pharmacovigilance database (EudraVigilance) with HCQ as suspected drug and related to adverse events belonging to the System Organ Class 'Psychiatric disorders' were shown. Over the years, evidence was published about the risk of neuropsychiatric clinical manifestations during HCQ treatment for rheumatic diseases, but few of them were related to elderly patients. These adverse events can include less severe clinical manifestations such as affect lability and nervousness or more severe conditions such as actual psychosis and suicidal tendencies, which frequency are actually unknown. The presence of risk factors in these patients may precipitate HCQ-induced psychosis and their precocious detection could be associated with a risk minimization. Among predisposing risk factors, there are the co-exposure to interacting drugs, alcohol intake, familial history of psychiatric diseases, female gender, and the concomitant use of low-dose glucocorticoids. In some cases it was possible to reverse psychotic behaviour with the antipsychotic treatment or with HCQ suspension.

Diagnostic value of salivary CRP and IL-6 in patients undergoing anti-TNF-alpha therapy for rheumatic disease

Abstract

Introduction

Saliva has been increasingly used as a diagnostic medium for disease detection and monitoring. The aim of this observational, prospective, pilot study was to investigate whether salivary concentrations of CRP and IL-6 correlate with those in serum and with the clinical course of a rheumatic disease.

Materials and methods

Nineteen patients with rheumatic disease newly scheduled for anti-TNFα therapy were included. Patients received anti-TNFα treatment (adalimumab, certolizumab, golimumab or infliximab) as per standard protocols. CRP and IL-6 were measured with high-sensitivity immunoassays before and after 12 weeks of therapy, according to standard regimens. The data were analyzed with nonparametric statistics.

Results

Concentrations of CRP in saliva correlated significantly with those in serum (R = 0.62; p < 0.0001) and decreased markedly after successful response to treatment. In patients with a limited response to treatment salivary CRP levels increased. In contrast to CRP, the salivary concentrations of IL-6 did not change significantly over the course of therapy and they did not correlate with serum IL-6 concentrations. Salivary levels of neither CRP nor IL-6 corresponded to parameters of oral health and hygiene.

Conclusions

Salivary CRP but not IL-6 could be of potential use for monitoring the rheumatic disease activity.

Molecular docking and pharmacological/toxicological assessment of a new compound designed from celecoxib and paracetamol by molecular hybridization

Abstract

Nonsteroidal anti-inflammatory drugs are commonly used worldwide; however, they have several adverse effects, evidencing the need for the development of new, more effective and safe anti-inflammatory and analgesic drugs. This research aimed to design, synthesize and carry out a pharmacological/toxicological investigation of LQFM-102, which was designed from celecoxib and paracetamol by molecular hybridization. To evaluate the analgesic effect of this compound, we performed formalin-induced pain, hot plate and tail flick tests. The anti-inflammatory effect of LQFM-102 was evaluated in carrageenan-induced paw oedema and pleurisy tests. The biochemical markers indicative of toxicity—AST, ALT, GSH, urea and creatinine—as well as the index of gastric lesion after prolonged administration of LQFM-102 were also analyzed. In addition, the interaction of LQFM-102 with COX enzymes was evaluated by molecular docking. In all experimental protocols, celecoxib or paracetamol was used as a positive control at equimolar doses to LQFM-102. LQFM-102 reduced the pain induced by formalin in both phases of the test. However, this compound did not increase the latency to thermal stimuli in the hot plate and tail flick tests, suggesting an involvement of peripheral mechanisms in this effect. Furthermore, LQFM-102 reduced paw oedema, the number of polymorphonuclear cells, myeloperoxidase activity and TNF-α and IL-1β levels. Another interesting finding was the absence of alterations in the markers of hepatic and renal toxicity or lesions of gastric mucosa. In molecular docking simulations, LQFM-102 interacted with the key residues for activity and potency of cyclooxygenase enzymes, suggesting an inhibition of the activity of these enzymes.

Management of Complex Arteriovenous Malformations Using a Novel Combination Therapeutic Algorithm

This case series assesses the efficacy and tolerability of sirolimus as an adjuvant therapy for endovascular embolization in the management of complicated extracranial head and neck arteriovenous malformations.

Translating Data on Trends in Disease Management to Decisions

Quantifying health care utilization is an important first step in understanding how to efficiently and effectively deliver health care to patients. Actinic keratoses (AKs) are among the most common clinical diagnoses encountered by dermatologists, and treatment aims to reduce patient discomfort and potential for malignant transformation. Given an aging population, disease burden will likely increase, highlighting the need for understanding trends in AK treatment and reimbursement.

Antiphospholipid Syndrome Following Pembrolizumab Treatment of Stage IIIB Unresectable Melanoma

The case report describes the occurrence of antiphospholipid syndrome following pembrolizumab treatment of stage IIIB unresectable melanoma.

Use of Actinic Keratosis Destruction in the Medicare Part B Fee-for-Service Population

This billing claims analysis uses the Medicare Part B Physician/Supplier Procedure Summary Master Files and National Summary Data to evaluate trends in the use and costs of actinic keratosis destruction.

Japanese guidelines for the management and treatment of generalized pustular psoriasis: The new pathogenesis and treatment of GPP

The Journal of Dermatology, EarlyView.

ECOTOX, new questions for terrestrial and aquatic ecotoxicology

“Market withdrawals” of medicines in Germany after AMNOG: a comparison of HTA ratings and clinical guideline recommendations

According to the AMNOG act, the German Federal Joint Committee (G-BA) determines the additional benefit of new medicines as a basis for subsequent price negotiations. Pharmaceutical companies may withdraw thei...

Occupational allergic contact dermatitis caused by colophonium

Contact Dermatitis, EarlyView.

Unusual skin manifestations associated with parvovirus B19 primary infection in children

Pediatric Dermatology, EarlyView.

Screening of candidate gene responses to cadmium stress by RNA sequencing in oilseed rape ( Brassica napus L.)

Abstract

Cadmium (Cd) stress is one of the most serious threats to agriculture in the world. Oilseed rape (Brassica napus L.) is an important oil crop; however, Cd can easily accumulate in rapeseed and thus harm human health through the food chain. In the first experiment, our purpose was to measure the Cd accumulation in mature B. napus plants and its influences on fatty acid composition. The results showed that most Cd was accumulated in the root, and the seed fatty acid content was considerably different at different Cd toxicity levels. In the second experiment, 7-day-old B. napus seedlings stressed by Cd (1 mM) for 0 h (CK-0h), 24 h (T-24h), or 72 h (T-72h) were submitted to physiological and biological analyses, RNA-Seq and qRT-PCR. In total, 5469 and 6769 differentially expressed genes (DEGs) were identified in the comparisons of "CK-0h vs T-24h" and "CK-0h vs T-72h", respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the photosynthetic and glutathione (GSH) pathways were significantly enriched in response to Cd stress. Key factors in the response to Cd stress included BnPCS1, BnGSTU12, BnGSTU5, and BnHMAs. The transcription factors BnWRKY11 (BnaA03g51590D), BnWRKY28 (BnaA03g43640D), BnWRKY33 (BnaA03g17820D), and BnWRKY75 (BnaA03g04160D) were upregulated after Cd exposure. The present study revealed that upregulation of the genes encoding GST and PCS under Cd stress promoted the formation of low-molecular weight complexes (PC-Cd), and upregulation of heavy metal ATPase genes induced PC-Cd transfer to vacuoles. These findings may provide the basis for the molecular mechanism of the response of B. napus to Cd.

Schmerzhafte Lymphadenopathie nach Insektenstich – ein Fallbericht

Zusammenfassung

Tularämie ist eine bakterielle Zoonose, die meist durch Zecken- und Insektenstiche oder durch Kontakt mit dem Fleisch infizierter Tiere übertragen wird. Wir berichten über einen 36-jährigen Patienten, der nach einem Insektenstich am Abdomen Fieber, Schüttelfrost, Kopfschmerzen und eine einseitige, schmerzhafte, inguinale Lymphadenopathie mit rötlich-livider Verfärbung der umgebenden Haut entwickelte. Die Diagnose einer ulzeroglandulären Tularämie wurde mittels Polymerasekettenreaktion (PCR) und Serologie gestellt. Es wurde eine 21-tägige Therapie mit Doxycyclin durchgeführt, die zur Abheilung führte.

Pseudoxanthoma elasticum: Dermoscopy and mutation analysis

Australasian Journal of Dermatology, EarlyView.

A rare cause of unilateral facial rash

Clinical and Experimental Dermatology, EarlyView.

A revisit of the environmental Kuznets curve hypothesis for Turkey: new evidence from bootstrap rolling window causality

Abstract

This study aims at analyzing the Environmental Kuznets Curve (EKC) hypothesis for Turkey, spanning the period of 1961–2013. Unlike previous studies, instead of carbon emissions, the ecological footprint is used as a proxy for environmental degradation. Moreover, a bootstrap time-varying causality approach is used to detect the possible changes in causal relations and to obtain the parameters across subsample periods. The results clearly indicate that there are feedback relationships between economic growth and the ecological footprint in some subsample periods. In addition, the impact of economic growth on environmental degradation is positive and has a slowly increasing trend in all subsample periods. Therefore, the EKC hypothesis is not confirmed for the Turkish economy. Based on these results, some crucial policy implications are suggested.