Revisiting Nāgārjuna’s Vigrahavyāvartanī

Abstract

In this paper, I attempt (1) a further elucidation and defense of some of the things I said in my article "Critical Reflections on Nāgārjuna's Vigrahavyāvartanī" (Sharma in Nagoya Stud Indian Cult Buddh 29:1–38, 2011) and (2) a response to Professor Claus Oetke's criticisms (J Indian Philos 40(4):371–394, 2012) of "a number of views which have been propagated" by me in my article. Although some additional issues have been raised, broadly, the themes addressed here are the same three as were the object of my investigation in that paper: namely, Nāgārjuna's emptiness (svabhāva–śūnyatā) doctrine; his denial that he has any thesis to advance or buttress; and his onslaught on the pramāṇa theory. Toward the end I argue that if I understand Nāgārjuna correctly, then what that thinker ends up providing is a criterion, not of reality, but of unreality, and that this stance, speaking philosophically, is tantamount to nihilism.

Palisading neutrophilic and granulomatous dermatitis as a presentation of Hodgkin lymphoma: A case and review

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a histopathological diagnosis, characterized by a pattern of granulomatosis, which may be associated with leukocytoclastic vasculitis. PNGD most commonly occurs in association with systemic inflammatory disorders, typically autoimmune conditions, such as rheumatoid arthritis and systemic lupus erythromatosus. There are very rare reports of PNGD in patients with lymphoma. We report the case of a 53-year-old female with an erythematous, papular eruption occurring in association with Hodgkin lymphoma. Histopathological evaluation of the rash confirmed PNGD. To the best of our knowledge, this is the first case of PNGD occurring in association with Hodgkin lymphoma. Although extremely rare, underlying malignancy should be considered in patients with PNGD, particularly in individuals with constitutional symptoms and the absence of an obvious inflammatory etiology.

Clinical characteristics of Japanese patients with psoriatic arthritis: Comparison with East Asian countries

Abstract

To determine the characteristics and current status of Japanese patients with psoriatic arthritis, the Japanese Society for Psoriasis Research have started to conduct retrospective questionnaire surveys. The results collected from over a thousand patients with psoriatic arthritis have revealed several characteristics. The newly visited psoriatic arthritis patients accounted for approximately 10% of all new psoriatic patients who visited the dermatology department in many referral centers. The prevalence was nearly 15% of psoriatic patients, which was similar to a recent rheumatology and dermatology study in Japan with a large cohort. There was a male predominance. The mean age of onset for cutaneous psoriasis was in the late 30s, while that of arthritis was in the late 40s. If we compare the precedence of cutaneous psoriasis versus arthritis, the psoriasis precedent group accounted for nearly 75%, while arthritis accounted for 5% of cases. The mean duration in patients who developed psoriasis prior to arthritis was over 10 years, while that in patients preceded by arthritis was less than 5 years. According to the Moll and Wright criteria, polyarthritis type was most common, followed by distal interphalangeal type and oligoarthritis type. Biologics were used in over 50% of psoriatic arthritis patients, and TNF inhibitors were currently used in approximately 70% among biologics. Switching to other biologics or discontinuance was seen in 15%. This review shows the current status of psoriatic arthritis in Japan, as well as a comparison of the prevalence among East Asian countries.

Systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by vasculopathy and tissue fibrosis of the skin and various internal organs. A series of genetic and epidemiological studies have demonstrated that SSc onset is determined by the accumulation of predisposing factors related to environmental influences, while genetic factors affect the susceptibility to and the severity of this disease. This notion has been confirmed by recent advance in animal models. The initial trigger of SSc is believed to be autoimmune attacks to endothelial cells, which occur in individuals with the genetic susceptibility to autoimmune diseases and/or the cumulative exposure to certain SSc-related environmental influences. Then, endothelial cells are aberrantly activated or damaged, leading to the development of vascular structural changes, such as destructive vasculopathy and proliferative obliterative vasculopathy, and tissue fibrosis. In parallel, inflammatory cells activate SSc fibroblasts and modify the metabolism of extracellular matrix by soluble factors and autoantibodies. Prior to or during these processes, SSc fibroblasts acquire the ability to selectively respond to profibrotic growth factors and cytokines, persistently producing excessive amount of extracellular matrix. SSc fibroblasts also modify immune responses, at least those of CD4⁺ T cells, in the microenvironment through the secretion of immune regulatory molecules. Thus, various types of individually activated cells interact with each other and coordinately drive an SSc-specific disease cascade, leading to the development of unique clinical symptoms. This article provides an overview of the current understanding of the pathogenesis of SSc with the recent advance in the research field of this disease.

Safety of biologics in psoriasis

Abstract

The advent of biologics brought a paradigm shift in ways to treat psoriatic patients because they have dramatic efficacy. At the same time, safety concerns about biologics have been raised. In this paper, we focus on the safety profile of biologics for psoriasis. As of 2017, six biologics are available in Japan. Two tumor necrosis factor-α inhibitors; infliximab and adalimumab, one anti-interleukin (IL)-12/23p40 antibody; ustekinumab, and IL-17 inhibitors; secukinumab, ixekizumab and brodalumab. Secukinumab and ixekizumab are anti-IL-17A antibodies. Brodalumab is an anti-IL17RA antibody. In this review, we pick up topics which have drawn attention regarding the safety of biologics and discuss them with recent published work.

Mouse models of psoriasis and their relevance

Abstract

Psoriasis is an inflammatory skin disorder that includes dynamic interactions between the immune system and skin and is clinically characterized by keratinocyte proliferation and distinct inflammatory cell infiltrates. Cross-talk between keratinocytes and immunocytes is essential for the development of psoriasis given that it mediates the production of cytokines, chemokines and growth factors. To resolve the pathogenesis of psoriasis, numerous experimental animal models have been generated. In this review, we discuss recent findings from mouse models, their relevancy to psoriasis and use, including the discovery of new therapies.

Pathogenesis of psoriasis and development of treatment

Abstract

The pathogenesis of psoriasis can be explained by dysregulation of immunological cell function as well as keratinocyte proliferation/differentiation. Recently, the immunological pathomechanism has been clarified substantially. Whereas T-helper (Th)1 overactivation was thought to induce occurrence of psoriasis, it has been demonstrated that Th17 cells play a key role. Th17 development is maintained by interleukin (IL)-23 mainly produced by dendritic cells. Th17 cells produce various cytokines, including IL-17A, IL-17F and IL-22. IL-17A and IL-22 induce not only keratinocyte proliferation, but also tumor necrosis factor (TNF)-α, chemokine (C-X-C motif) ligand (CXCL)1 and CXCL8 production. TNF-α accelerates the infiltration of inflammatory cells, including lymphocytes, monocytes and neutrophils, from the peripheral blood into skin with dendritic cell activation. In addition, antimicrobial peptides are overexpressed in psoriatic skin lesions, and the antimicrobial peptide, LL-37, activates dendritic cells, which leads to the development of inflammation. Furthermore, activation of nuclear factor-κB signal induces the expression of keratins 6 and 16 in keratinocytes, which are associated with acanthosis and reduced turnover time in the epidermis. The progression of the pathomechanism contributes to the development of new therapies for psoriasis.

Exploring Facets of Flavor

Development of Children’s Olfactory Abilities and Odor Awareness Is Not Predicted by Temperament: a Longitudinal Study

Abstract

Introduction

Temperament affects olfaction in cross-sectional studies. However, it is not clear whether it is linked to olfactory development. Here we examined the links between temperament and olfaction over a nearly 2-year period, expecting that children showing higher levels of negative affectivity would exhibit greater odor awareness across repeated testing. As a subsidiary aim, we investigated whether olfactory scores differ as a function of olfactory performance at a younger age.

Methods

The participants were 73 Czech children (mean age = 5.8 years). Their olfactory abilities were assessed using the Sniffin' Sticks, and odor awareness was evaluated with the Children's Olfactory Behaviors in Everyday Life Questionnaire. These were reassessed 21 months later. Mothers provided information on the children's temperament by completing the Short Form of the Children's Behavior Questionnaire at the same interval.

Results

Children's temperament was not found to relate to olfactory development over a 21-month period. Odor identification and awareness, but not odor discrimination and threshold, differed as a function of scores achieved at an earlier age.

Conclusions

Odor identification and awareness predict themselves over a 21-month period. Links between temperament and olfaction may be only beginning to form at preschool age.

Implications

While this study suggests that temperament does not play a role in olfactory development, longitudinal studies over a broader timespan are needed to determine the robustness of this finding.

Microneedling combined with platelet-rich plasma or trichloroacetic acid peeling for management of acne scarring: A split-face clinical and histologic comparison

Summary

Background

Minimally invasive procedures provide effective, safe, relatively long-lasting, and natural results without large damage to the skin. A combination treatment is considered an approach that includes at least 2 different and unrelated modalities.

Objectives

This study aims to evaluate the use and effectiveness of some combined minimally invasive procedures for management of acne scarring.

Patients/methods

Twenty-four volunteers with postacne atrophic scars were randomly divided into 3 equal groups according to performed procedure on each side of the face (microneedling by dermaroller alone or combined with platelet-rich plasma [PRP] or trichloroacetic acid [TCA] 15% peeling) and received 6 bi-weekly sessions of treatment. Photography and punch biopsies were taken before and after 3 months of treatment for clinical, histological, and histometrical evaluation.

Results

Combined treatment of dermaroller and PRP or dermaroller and TCA 15% showed significant improvement when compared with dermaroller alone (P = .015 and .011 respectively). Epidermal thickness showed statistically significant increase in studied groups, mainly after dermaroller and TCA 15%. Moreover, the 3 studied groups showed more organized collagen bundles and newly formed collagen formation and markedly decreased abnormal elastic fibers.

Conclusions

Based on the clinical, histometrical, and histochemical assessment, inspite that most volunteers showed significant improvement after treatment, however, the combined use of dermaroller and TCA 15% was more effective in postacne atrophic scars than the use of dermaroller and PRP or dermaroller only.

Non-BRCA1/2 Breast Cancer Susceptibility Genes: A New Frontier with Clinical Consequences for Plastic Surgeons

Summary: Twenty percent of breast cancer cases may be related to a genetic mutation conferring an increased risk of malignancy. The most common and prominent breast cancer susceptibility genes are BRCA1 and BRCA2, found in nearly 40% of such cases. However, continued interest and investigation of cancer genetics has led to the identification of a myriad of different breast cancer susceptibility genes. Additional genes, each with unique significance and associated characteristics, continue to be recognized. Concurrently, advanced genetic testing, while still controversial, has become more accessible and cost-effective. As oncologic and reconstructive advances continue to be made in prophylactic breast reconstructive surgery, patients may present to plastic surgeons with an increasingly more diverse array of genetic diagnoses to discuss breast reconstruction. It is therefore imperative that plastic surgeons be familiar with these breast cancer susceptibility genes and their clinical implications. We, therefore, aim to review the most common non-BRCA1/2 breast cancer susceptibility genetic mutations in an effort to assist plastic surgeons in counseling and managing this unique patient population. Included in this review are syndromic breast cancer susceptibility genes such as TP53, PTEN, CDH1, and STK11, among others. Nonsyndromic breast cancer susceptibility genes herein reviewed include PALB2, CHEK2, and ataxia telangiectasia mutated gene. With this knowledge, plastic surgeons can play a central role in the diagnosis and comprehensive treatment, including successful breast reconstruction, of all patients carrying genetic mutations conferring increased risk for breast malignancies.

Therapeutic effects of a pulsed electromagnetic device in chronic cutaneous ulcers of the lower limbs

Publication date: Available online 9 December 2017
Source:Wound Medicine
Author(s): Edoardo Raposio, Nicolò Bertozzi, Francesco Simonacci, Michele P. Grieco
We conducted a randomized, prospective pilot study to evaluate the therapeutic effects (in particular, wound healing rate and pain relief) of one device that administers topical millimeter waves (MW) in patients with chronic skin ulcers of the lower extremities. Twenty consecutive patients with chronic skin ulcers of the lower extremities were enrolled in the study and were assigned alternatingly into two groups (experimental and control) as they randomly arrived at the clinic. For patients assigned to the experimental group, a fully-functioning device was applied; whereas, patients in the control group had a similar but nonfunctioning device applied. There was a statistically significant difference between pain values of the control and experimental groups after one month (t4) (p=0.045), as well as between experimental group NRS values at t0 and t4 (p=0.035).

Impact of Fire Suit Ensembles on Firefighter PAH Exposures as Assessed by Skin Deposition and Urinary Biomarkers

Abstract

Over the past 10 years, a number of safety measures for reducing firefighters' exposure to combustion particles have been introduced in Sweden. The most important measure was the reduction in the time firefighters wear suits and handle contaminated equipment after turn-outs involving smoke diving. This study was divided into two parts, those being to investigate the level of protection obtained by multiple garment layers and to assess exposure during a standardized smoke diving exercise. First, realistic work protection factors (WPFs) were calculated by comparing air concentrations of the full suite of gaseous and particle-bound polycyclic aromatic hydrocarbons (PAHs) inside and outside structural ensembles, including jacket and thick base layer, during a tough fire extinguishing exercise using wood as the fuel. Second, during a standardized smoke diving exercise, exposure was assessed by measuring PAH skin deposition and levels of eight urinary PAH metabolites in 20 volunteer student firefighters before and after the exercise. The average WPF for the sum of 22 PAHs was 146 ± 33 suggesting a relatively high protective capacity but also indicating a substantial enrichment of contaminants with a risk of prolonged dermal exposure. Accordingly, in the second exercise, the median levels of skin-deposited Σ14-PAHs and urinary 1-hydroxypyrene significantly increased 5-fold (21 to 99 ng/wipe) and 8-fold (0.14 to 1.1 µmol mol⁻¹ creatinine), respectively, post exposure. Among the PAH metabolites investigated, 1-hydroxypyrene proved to be the most useful indicator of exposure, with significantly elevated urinary levels at both 6 h and 20 h after the exercise and with the strongest correlation to dermal exposure. Metabolites from two-ring and three-ring PAHs were eliminated faster while levels of 3-hydroxy-benzo[a]pyrene did not meet the detection criteria. The results from correlation studies indicated that dermal uptake was a major route of exposure in accordance with previous findings. To summarize, this study shows that some of the newly adopted protective measures were correctly implemented, and should continue to be followed and be more widely adopted.

Aspergillus fumigatus-sensitive IgE is associated with bronchial hypersensitivity in a murine model of neutrophilic airway inflammation

Publication date: Available online 7 December 2017
Source:Journal de Mycologie Médicale
Author(s): G. Morán, B. Uberti, A. Ortloff, H. Folch
Neutrophils are the predominant inflammatory cells that infiltrate airways during acute exacerbation of asthma. The importance of A. fumigatus sensitization, and IgE response in the airways in patients with acute asthma is unclear. Rockefeller (RK) mice were sensitized with A. fumigatus extract protein. The animals were subsequently challenged with different degrees of A. fumigatus contamination in the cage bedding. All groups of mice were euthanized to obtain bronchoalveolar lavage fluid (BALF) for cytological and Elisa assays, and lung tissue for histological analysis. Moreover, several bioassays were conducted to determine whether BALF IgE antibodies can activate mast cells. In this study, we demonstrated that exposure of sensitized mice to a known concentration of A. fumigatus conidia produces bronchial hyperreactivity with marked neutrophilic bronchial infiltration and increased BALF IgE, capable of triggering mast cell degranulation. This study suggests that IgE may play a role in bronchial hyperreactivity associated to A. fumigatus exposure in mice. Mice sensitized and challenged with this fungus showed characteristics of severe asthma, with an increase of BALF neutrophils, histological changes consistent with severe asthma and an increase of IgE capable of triggering type I hypersensitivity.

Histatin-5 induces the reversal of Pdr5p mediated fluconazole resistance in Saccharomyces cerevisae

Publication date: Available online 6 December 2017
Source:Journal de Mycologie Médicale
Author(s): J.A. da Rocha Curvelo, L.F. Reis de Sá, D.C. Clemente de Moraes, R.M. Soares, A. Ferreira-Pereira
BackgroundCandidiasis is a major opportunistic fungal infection in humans. The low number of antifungal drugs available to treat Candida infections and the increasing incidence of multidrug resistant (MDR) strains point to an urgent need of identifying new therapeutic options. The role of salivary components can provide insights for the development of new methodologies of control.ObjectiveThe aim of this study was to evaluate the ability of histatin-5, a constitutive immunological peptide present in saliva, in reversing fungal MDR phenotype, using a resistant Saccharomyces cerevisiae strain as model of study.ResultsA total of 2.5μg and 5μg of histatin-5 revealed to be able to chemosensitize (to revert antifungal resistance) a MDR strain to fluconazole impairing its intrinsic resistance. The presence of histatin-5 decreased the strain growth when associated to fluconazole, and also assisted in the retention of rhodamine 6G within cell cytoplasm. The ATPase activity of Pdr5p, an ABC efflux transporter, was significantly reduced up to 65% within physiological concentration of the peptide.ConclusionResults revealed that histatin-5 is able to revert MDR phenotype and may be considered a potential alternative MDR inhibitor. Since Pdr5p is homologous to Candida albicans CaCdr1p and CaCdr2p, data obtained might be extrapolated to these transporters, inferring that associating fluconazole and histatin-5 may be a useful tool to circumvent failure treatments of infections caused by Candida MDR strains.

Editorial Board

Publication date: December 2017
Source:Journal de Mycologie Médicale, Volume 27, Issue 4

Povidone iodine soaked gelfoam for the treatment of recalcitrant otomycosis – Our experiences at a tertiary care teaching hospital of eastern India

Publication date: Available online 7 December 2017
Source:Journal de Mycologie Médicale
Author(s): S.K. Swain, I.C. Behera, M.C. Sahu, A. Das
IntroductionOtomycosis is a common clinical condition seen in outpatient department of otorhinolaryngology. The treatment of the otomycosis is also very simple. However, sometime it is difficult to treat otomycosis along with mastoid cavity, chronic suppurative otitis media, immunocompromised patient, etc. with conventional treatment, called recalcitrant otomycosis. Here, we describe a technique of treatment for recalcitrant otomycosis.Materials and methodsThis is a prospective observational study/clinical trial carried out on 44 patients of recalcitrant otomycosis. They are divided into two groups, each of 22. One group treated with routine clotrimazole topical eardrops whereas other group treated with povidone iodine soaked gelfoam, placed in the external auditory canal.ResultsThere was no significance difference according to the age (P=0.134), gender (P=0.760) and causative agents (P=0.750) between treatment groups. The resolution of the symptoms showed statistically significant on itching (P=0.0001), otorrhoea (P=0.0033), fullness (P=0.0432) and earache (P=0.0259), whereas no statistical significant on hearing loss (P=0.0683), when treating with povidone iodine soaked gelfoam as compared to routine (clotrimazole) treatment. Resolution of signs like canal wall erythema (P=0.0045), tragal tenderness (P=0.0012) and congestion of tympanic membrane (P=0.0088) is statistically significant when comparing clotrimazole with povidone iodine. Apart from these, we did not reveal any adverse effects from the study populations treated with povidone iodine soaked gelfoam.ConclusionUse of the povidone iodine soaked gelfoam at the external auditory canal in recalcitrant otomycosis is an effective and well-tolerated treatment.

Luliconazole, a new antifungal against Candida species isolated from different sources

Publication date: Available online 29 November 2017
Source:Journal de Mycologie Médicale
Author(s): S. Taghipour, N. Kiasat, S. Shafiei, M. Halvaeezadeh, A. Rezaei-Matehkolaei, A. Zarei Mahmoudabadi
ObjectiveLuliconazole is an inhibitor for sterol 14-α-demethylase in fungal cells with a broad-spectrum antifungal activity against dermatophytes, Candida albicans, Malassezia species, dematiaceous and hyaline hyphomycetes. Furthermore, luliconazole has been clinically used for the treatment of pityriasis versicolor, dermatophytosis, onychomycosis, cutaneous and mucocutaneous candidiasis. In the present study, we aimed to evaluate in vitro antifungal activity of luliconazole against several strains of Candida species recovered from different clinical materials.Materials and methodsIn the present study, 104 strains of Candida species including, 34 isolates from vaginitis, 23 isolates from AIDS patients with vaginal candidiasis, 24 isolates from neutropenic patients and 24 isolates from tracheal tubes, were examined for susceptibility tests. A serial dilution of luliconazole (4–0.008μg/mL) was tested against different strains of Candida species recovered from different sources.ResultsThe minimum inhibitory concentration (MIC) range and MIC90 of vaginal isolates (HIV⁻) were 1–0.063 and 1μg/mL. Furthermore, the most of strains (50%) had a MIC of 0.5μg/mL. The MIC ranges were similar (2–0.016μg/mL) for both vaginal (HIV⁺) and neutropenic patients isolates, whereas, MIC90 for them were 0.5 and 1μg/mL, respectively. All tracheal tubes strains were inhibited at the range of 2–0.008μg/mL with MIC90=1μg/mL. Totally, the lowest MIC50 (MIC=0.015μg/mL), MIC90 (MIC=1μg/mL) and MICGM (MIC=0.05μg/mL) are correlated to C. glabrata, a non-albicans species.ConclusionIt is concluded that, luliconazole could be an alternative anti-Candida agent, however, in vivo studies must be confirmed usefulness of drug for clinical usage.

page informations

Publication date: December 2017
Source:Journal de Mycologie Médicale, Volume 27, Issue 4

Oligomycins A and E, major bioactive secondary metabolites produced by Streptomyces sp. strain HG29 isolated from a Saharan soil

Publication date: Available online 20 November 2017
Source:Journal de Mycologie Médicale
Author(s): N. Khebizi, H. Boudjella, C. Bijani, N. Bouras, H.-P. Klenk, F. Pont, F. Mathieu, N. Sabaou
An actinobacterial strain, HG29, with potent activity against pathogenic, toxigenic and phytopathogenic fungi was isolated from a Saharan soil sample of Algeria. On the basis of morphological and chemotaxonomic characteristics, the strain was classified in the genus Streptomyces. Analysis of the 16S rRNA gene sequence showed a similarity level of 99.3% with Streptomyces gancidicus NBRC 15412^T. The comparison of its cultural and physiological characteristics with this species revealed significant differences. Moreover, the phylogenetic tree showed that strain HG29 forms a distinct phyletic line within the genus Streptomyces. Production of antifungal activity was investigated by following kinetics in shake broth. The highest antifungal activity was obtained after five days of fermentation, and in the dichloromethane extract. Two active compounds, NK1 and NK2, were purified by HPLC using a C18 column. Their chemical structures were identified through nuclear magnetic resonance experiments and mass spectrometry as oligomycins E and A, respectively, which have not been reported to be produced by S. gancidicus. The two bioactive compounds exhibited significant antifungal activity in vitro, showing minimal inhibitory concentrations (MICs) values between 2 and 75μg/mL.