Neuro-Oncology Diet and risk of glioma

Estimating survival for renal cell carcinoma patients with brain metastases: an update of the Renal Graded Prognostic Assessment tool
Brain metastases are a common complication of renal cell carcinoma (RCC). Our group previously published the Renal Graded Prognostic Assessment (GPA) tool. In our prior RCC study (n = 286, 1985–2005), we found marked heterogeneity and variation in outcomes. In our recent update in a larger, more contemporary cohort, we identified additional significant prognostic factors. The purpose of this study is to update the original Renal-GPA based on the newly identified prognostic factors.Methods
A multi-institutional retrospective institutional review board–approved database of 711 RCC patients with new brain metastases diagnosed from January 1, 2006 to December 31, 2015 was created. Clinical parameters and treatment were correlated with survival. A revised Renal GPA index was designed by weighting the most significant factors in proportion to their hazard ratios and assigning scores such that the patients with the best and worst prognoses would have a GPA of 4.0 and 0.0, respectively.Results
The 4 most significant factors were Karnofsky performance status, number of brain metastases, extracranial metastases, and hemoglobin. The overall median survival was 12 months. Median survival for GPA groups 0–1.0, 1.5–2.0, 2.5–3, and 3.5–4.0 (% n = 25, 27, 30 and 17) was 4, 12, 17, and 35 months, respectively.Conclusion
The updated Renal GPA is a user-friendly tool that will help clinicians and patients better understand prognosis, individualize clinical decision making and treatment selection, provide a means to compare retrospective literature, and provide more robust stratification of future clinical trials in this heterogeneous population. To simplify use of this tool in daily practice, a free online application is available at brainmetgpa.com.

Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients
Peptide vaccines offer the opportunity to elicit glioma-specific T cells with tumor killing ability. Using antigens eluted from the surface of glioblastoma samples, we designed a phase I/II study to test safety and immunogenicity of the IMA950 multipeptide vaccine adjuvanted with poly-ICLC in HLA-A2 + glioma patients.Methods
Adult patients with newly diagnosed glioblastoma (n=16) and grade III astrocytoma (n=3) were treated with radiochemotherapy followed by IMA950/poly-ICLC vaccination. The first 6 patients received IMA950 (9 MHC class I and 2 MHC class II peptides) i.d. and poly-ICLC i.m. After protocol amendment, IMA950 and poly-ICLC were mixed and injected s.c. (n=7) or i.m. (n=6). Primary endpoints were safety and immunogenicity. Secondary endpoints were overall survival, progression-free survival at 6 and 9 months, and vaccine-specific peripheral CD4 and CD8 T cell responses.Results
The IMA950/poly-ICLC vaccine was safe and well tolerated. Four patients presented cerebral edema with rapid recovery. For the first 6 patients, vaccine-induced CD8 T cell responses were restricted to a single peptide and CD4 responses were absent. After optimization of vaccine formulation, we observed multipeptide CD8 and sustained Th1 CD4 T cell responses. For the entire cohort, CD8 T cell responses to a single or multiple peptides were observed in 63.2% and 36.8% of patients, respectively. Median overall survival was 19 months for glioblastoma patients.Conclusion
We provide, in a clinical trial, using cell surface-presented antigens, insights into optimization of vaccines generating effector T cells for glioma patients.Trial registration
Clinicaltrials.gov NCT01920191.
Recent Developments and Future Directions in Adult Lower-Grade Gliomas: Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) Consensus
The finding that most grade II and III gliomas harbor isocitrate dehydrogenase (IDH) mutations conveying a relatively favorable and fairly similar prognosis in both tumor grades highlights that these tumors represent a fundamentally different entity from IDH wild-type gliomas exemplified in most glioblastoma. Herein we review the most recent developments in molecular neuropathology leading to reclassification of these tumors based upon IDH and 1p/19q status, as well as the potential roles of methylation profiling and CDKN2A/B deletional analysis. We discuss the epidemiology, clinical manifestations, benefit of surgical resection, and neuroimaging features of lower-grade gliomas as they relate to molecular subtype, including advanced imaging techniques such as 2-hydroxyglutarate magnetic resonance spectroscopy and amino acid PET scanning. Recent, ongoing and planned studies of radiation therapy and both cytotoxic and targeted chemotherapies are summarized, including both small molecule and immunotherapy approaches specifically targeting the mutant IDH protein.

Diet and risk of glioma: combined analysis of three large prospective studies in the UK and USA
Available evidence on diet and glioma risk comes mainly from studies with retrospective collection of dietary data. To minimise possible differential dietary recall between those with and without glioma, we present findings from three large prospective studies.Methods
Participants included 692,176 from (UK) Million Women Study, 470,780 from (US) NIH-AARP Study, and 99,148 from (US) PLCO Study. Cox regression yielded study-specific adjusted relative risks for glioma in relation to 15 food groups, 14 nutrients, and 3 dietary patterns, which were combined, weighted by inverse-variances of the relative risks. Separate analyses by <5 and ≥5 years follow-up assessed potential biases related to changes of diet before glioma diagnosis.Results
The 1,262,104 participants, mean age 60.6 (SD5.5) at baseline, were followed for 15.4 million person-years (mean 12.2 years/participant), during which 2,313 incident gliomas occurred, at mean age 68.2 (SD6.4). Overall, there was weak evidence for increased glioma risks associated with increasing intakes of total fruit, citrus fruit, and fibre, and healthy dietary patterns, but these associations were generally null after excluding the first 5 years of follow-up. There was little evidence for heterogeneity of results by study or by sex.Conclusions
The largest prospective evidence to date suggests little, if any, association between major food groups, nutrients, or common healthy dietary patterns, and glioma incidence. With the statistical power of this study and the comprehensive nature of the investigation here, it seems unlikely we have overlooked major effects of diet on risk of glioma that would be of public health concern.
Highlights from the Literature
Forthcoming Meetings
Edited by Albert H. Kim and Jennie W. Taylor
Glioblastoma: a prognostic value of AMT-PET?
See the article by John et al, pp. 264–273.
Old meet new—the path to combination treatments in pediatric low-grade gliomas
See the article by Poore et al, pp. 252–263.
Disparities along the glioblastoma clinical trials landscape
We read with interest the recent work by Vanderbeek et al1 regarding the current clinical trials landscape for glioblastoma (GBM) patients. An unexplored dimension of their analysis centers on disparities and demographic discrepancies between clinical trial participants and the broader GBM population. We therefore examined clinical trials with published results as highlighted by the authors, totaling 51 trials.1 While most of these trials reported details regarding patient age (48/51, 94%) and gender (47/51, 92%), only 14 trials (27%) provided information regarding ethnicity and/or race in either peer-reviewed publications or ClinicalTrials.gov. The rate of reporting ethnicity/race was particularly low among phase I/II studies (9/43, 21%) compared with phase III trials (5/8, 63%, chi-squared test P = 0.02).
Multimodal imaging-defined subregions in newly diagnosed glioblastoma: impact on overall survival
Although glioblastomas are heterogeneous brain-infiltrating tumors, their treatment is mostly focused on the contrast-enhancing tumor mass. In this study, we combined conventional MRI, diffusion-weighted imaging (DWI), and amino acid PET to explore imaging-defined glioblastoma subregions and evaluate their potential prognostic value.Methods
Contrast-enhanced T1, T2/fluid attenuated inversion recovery (FLAIR) MR images, apparent diffusion coefficient (ADC) maps from DWI, and alpha-[11C]-methyl-L-tryptophan (AMT)-PET images were analyzed in 30 patients with newly diagnosed glioblastoma. Five tumor subregions were identified based on a combination of MRI contrast enhancement, T2/FLAIR signal abnormalities, and AMT uptake on PET. ADC and AMT uptake tumor/contralateral normal cortex (T/N) ratios in these tumor subregions were correlated, and their prognostic value was determined.Results
A total of 115 MRI/PET-defined subregions were analyzed. Most tumors showed not only a high-AMT uptake (T/N ratio > 1.65, N = 27) but also a low-uptake subregion (N = 21) within the contrast-enhancing tumor mass. High AMT uptake extending beyond contrast enhancement was also common (N = 25) and was associated with low ADC (r = −0.40, P = 0.05). Higher AMT uptake in the contrast-enhancing tumor subregions was strongly prognostic for overall survival (hazard ratio: 7.83; 95% CI: 1.98–31.02, P = 0.003), independent of clinical and molecular genetic prognostic variables. Nonresected high-AMT uptake subregions predicted the sites of tumor progression on posttreatment PET performed in 10 patients.Conclusions
Glioblastomas show heterogeneous amino acid uptake with high-uptake regions often extending into non-enhancing brain with high cellularity; nonresection of these predict the site of posttreatment progression. High tryptophan uptake values in MRI contrast-enhancing tumor subregions are a strong, independent imaging marker for longer overall survival.
Supratotal resection in glioma: a systematic review
Emerging evidence suggests survival benefit from resection beyond all MRI abnormalities present on T1-enhanced and T2‒fluid attenuated inversion recovery (FLAIR) modalities in glioma (supratotal resection); however, the quality of evidence is unclear. We addressed this question via systematic review of the literature.Methods
EMBASE, MEDLINE, Scopus, and Web of Science databases were queried. Case studies, reviews or editorials, non-English, abstract-only, brain metastases, and descriptive works were excluded. All others were included.Results
Three hundred and nine unique references yielded 41 studies for full-text review, with 7 included in the final analysis. Studies were mostly of Oxford Center for Evidence-Based Medicine Level 4 quality. A total of 88 patients underwent supratotal resection in a combined cohort of 492 patients (214 males and 278 females, age 18 to 82 years). Fifty-one supratotal resections were conducted on high-grade gliomas, and 37 on low-grade gliomas. Karnofsky performance status, overall survival, progression-free survival, neurological deficits postoperatively, and anaplastic transformation were the main measured outcomes. No randomized controlled trials were identified. Preliminary low-quality support was found for supratotal resection in increasing overall survival and progression-free survival for both low-grade and high-grade glioma.Conclusion
The literature suggests insufficient evidence for carte blanche application of supratotal resection, particularly in lower-grade gliomas where neurological deficits can result in long-term disability. While the preliminary studies discussed here, containing data from only a few centers, have reported increased progression-free and overall survival, these claims require validation in prospective research studies involving larger patient populations with clearly defined appropriate outcome metrics in order to reduce potential bias.
Uncommon low-grade brain tumors
The 2016 World Health Organization (WHO) classification of primary central nervous system (CNS) tumors includes numerous uncommon (representing ≤1% of tumors) low-grade (grades I–II) brain neoplasms with varying clinical behaviors and outcomes. Generally, gross tumor or maximal safe resection is the primary treatment. Adjuvant treatments, though their exact role is unknown, may be considered individually based on pathological subtypes and a proper assessment of risks and benefits. Targetable mutations such as BRAF (proto-oncogene B-Raf), TRAIL (tumor necrosis factor apoptosis inducing ligand), and PDGFR (platelet derived growth factor receptor) have promising roles in future management.
Outcomes following stereotactic radiosurgery for small to medium-sized brain metastases are exceptionally dependent upon tumor size and prescribed dose
At our institution, we have historically treated brain metastasis (BM) ≤2 cm in eloquent brain with a radiosurgery (SRS) lower prescription dose (PD) to reduce the risk of radionecrosis (RN). We sought to evaluate the impact of this practice on outcomes.Methods
We analyzed a prospective registry of BM patients treated with SRS between 2008 and 2017. Incidences of local failure (LF) and RN were determined and Cox regression was performed for univariate and multivariate analyses (MVAs).Results
We evaluated 1533 BM ≤2 cm. Median radiographic follow-up post SRS was 12.7 months (1.4–100). Overall, the 2-year incidence of LF was lower for BM treated with PD ≥21 Gy (9.3%) compared with PD ≤15 Gy (19.5%) (sub–hazard ratio, 2.3; 95% CI: 1.4–3.7; P = 0.0006). The 2-year incidence of RN was not significantly higher for the group treated with PD ≥21 Gy (9.5%) compared with the PD ≤15 Gy group (7.5%) (P = 0.16). MVA demonstrated that PD (≤15 Gy) and tumor size (>1 cm) were significantly correlated (P < 0.05) with higher rates of LF and RN, respectively. For tumors ≤1 cm, when comparing PD ≤15 Gy with ≥21 Gy, the risks of LF and RN are equivalent. However, for lesions >1 cm, PD ≥21 Gy is associated with a lower incidence of LF without significantly increasing the risk of RN.Conclusion
Our results indicate that rates of LF or RN following SRS for BM are strongly correlated with size and PD. Based on our results, we now, depending upon the clinical context, consider increasing PD to 21 Gy for BM in eloquent brain, excluding the brainstem.
Sex difference of mutation clonality in diffuse glioma evolution
Sex differences in glioma incidence and outcome have been previously reported but remain poorly understood. Many sex differences that affect the cancer risk were thought to be associated with cancer evolution.Methods
In this study, we used an integrated framework to infer the timing and clonal status of mutations in ~600 diffuse gliomas from The Cancer Genome Atlas (TCGA) including glioblastomas (GBMs) and low-grade gliomas (LGGs), and investigated the sex difference of mutation clonality.Results
We observed higher overall and subclonal mutation burden in female patients with different grades of gliomas, which could be largely explained by the mutations of the X chromosome. Some well-established drivers were identified showing sex-biased clonality, such as CDH18 and ATRX. Focusing on glioma subtypes, we further found a higher subclonal mutation burden in females than males in the majority of glioma subtypes, and observed opposite clonal tendency of several drivers between male and female patients in a specific subtype. Moreover, analysis of clinically actionable genes revealed that mutations in genes of the mitogen-activated protein kinase (MAPK) signaling pathway were more likely to be clonal in female patients with GBM, whereas mutations in genes involved in the receptor tyrosine kinase signaling pathway were more likely to be clonal in male patients with LGG.Conclusions
The patients with diffuse glioma showed sex-biased mutation clonality (eg, different subclonal mutation number and different clonal tendency of cancer genes), highlighting the need to consider sex as an important variable for improving glioma therapy and clinical care.

Dangerous non-food products,European Commission Safety Gate : Products with serious risks Click to enlarge 1 of 1 photo Share on Alert number: A12/0283/19 Category: Hobby/sports equipment Product: Electric scooter (e-kick board) Brand: IKEA Name: PENDLA Type / number of model: Article no 10395275 Batch number / Barcode: Unknown Risk type: Injuries The foot board of the scooter is not sufficiently strong. It could break while the scooter is in use, causing the user to fall. The product does not comply with the requirements of the Machinery Directive. Measures taken by economic operators: Recall of the product from end users (By: Manufacturer) Company recall page: https://m2.ikea.com/se/sv/customer-service/produktaterkallelser-pube5a0a321 Click to enlarge 1 of 3 photos Previous Next Share on Alert number: A12/0287/19 Category: Hobby/sports equipment Product: Self-balancing scooter (Hoverboard) Brand: Unknown Name: Smart Balance Wheel Type / number of model: Scooter: Item No: V7 Power


Dangerous non-food products,European Commission Safety Gate : Products with serious risks Click to enlarge 1 of 1 photo Share on Alert number: A12/0283/19 Category: Hobby/sports equipment Product: Electric scooter (e-kick board) Brand: IKEA Name: PENDLA Type / number of model: Article no 10395275 Batch number / Barcode: Unknown Risk type: Injuries The foot board of the scooter is not sufficiently strong. It could break while the scooter is in use, causing the user to fall. The product does not comply with the requirements of the Machinery Directive. Measures taken by economic operators: Recall of the product from end users (By: Manufacturer) Company recall page: https://m2.ikea.com/se/sv/customer-service/produktaterkallelser-pube5a0a321 Click to enlarge 1 of 3 photos Previous Next Share on Alert number: A12/0287/19 Category: Hobby/sports equipment Product: Self-balancing scooter (Hoverboard) Brand: Unknown Name: Smart Balance Wheel Type / number of model: Scooter: Item No: V7 Power


Endocrinology’s best articles of 2018 : Adipose tissue in control of metabolism by Liping Luo and Meilian Liu. M icrovesicles and exosomes: new players in metabolic and cardiovascular disease by Charlotte Lawson et al. Insulin resist ance and sarcopenia: mechanistic links between common co-morbidities by Mark E Cleasby, Pauline M Jamieson and Philip J Atherton. , Current understanding of metformin effect on the control of hyperglycemia in diabetes by Hongying An and Lin g He. , Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action by Geoffrey L Hammond. , Thyroid hormones induce browning of white fat by Noelia Martínez-Sánchez et al. , Sodium butyrate activates NRF2 to ameliorat e diabetic nephropathy possibly via inhibition of HDAC by Wenpeng Dong et al. , Leptin stimulates bone formation in ob/o b mice at doses having minimal impact on energy metabolism Kenneth A Philbrick et al. , IGFBP-4 regulates adult skeletal growth in a sex-specific manner b

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Current understanding of metformin effect on the control of hyperglycemia in diabetes by Hongying An and Ling He.
Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action by Geoffrey L Hammond.
Thyroid hormones induce browning of white fat by Noelia Martínez-Sánchez et al.
Sodium butyrate activates NRF2 to ameliorate diabetic nephropathy possibly via inhibition of HDAC by Wenpeng Dong et al.
Leptin stimulates bone formation in ob/ob mice at doses having minimal impact on energy metabolism Kenneth A Philbrick et al.
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Medical Trichology : Trigeminal trophic syndrome simulating pityriasis amiantacea,Nerve sheath myxoma of scalp,Woolly hair nevus type 2,Trichodynia silenced effectively with propranolol,Serum interleukin-15 is a marker of alopecia areata severity,Tubular hair casts in trichoscopy of hair and scalp disorders,Research on the balance of thiol-disulfide in blood serum in women with telogen effluvium,Light microscopic morphology of hair from scalp, eyebrow, axilla, and pubic regions

Autistic-undisciplined thinking in the practice of medical trichology p. 1
Ralph Michel Trueb, Hudson Dutra, Maria Fernanda Reis Gavazzoni Dias
DOI:10.4103/ijt.ijt_79_18 Medical trichology is the branch of dermatology that deals with the scientific study of the hair and scalp in health and disease. As any discipline, the practice of medical trichology is not immune to malpractice, either deliberately or carelessly. In his publication “Autistic Undisciplined Thinking in Medicine and How to Overcome It,” Swiss psychiatrist Eugen Bleuler describes yet another form of malpractice in medicine reflecting autistic-undisciplined thinking. Autism is not limited to psychopathology, but inherent to the thinking of man throughout history in his drive for knowledge, with thousands of theories lacking any basis in reality. Bleuler recognized the drive character of autistic thinking and how it leads to conclusions that are unshakable because they are determined by, and fulfill, emotional needs, rather than rational argumentation. Even with correct questions, the complexity and incalculability of some problems are often so great that it cannot do justice to realistic thinking and the boundaries between inadequately substantiated hypothesis and autistic sham explanation disappear. Statistics, careful research design, and the attempt to impose stringent methods on our thinking are to be commended. The habituation of the public to useless medicine, to misconceptions, is not hygiene, but negligent endangerment. It has created an industry that largely lives on the autistic thinking of patients and doctors and because it is prosperous, makes propaganda among lay people as well as among doctors that necessarily leads to abuses. This article aims at exposing the most prevalent among abuses in trichological practice due to autistic-undisciplined thinking, specifically: iron supplementation, antiandrogenic treatment, and individualized cell-based therapy in female androgenetic alopecia, treatment of folliculitis decalvans with retinoids, and the value of nutritional therapies.
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zoom.png Light microscopic morphology of indigenous Ghanaian African hair from scalp, eyebrow, axilla, and pubic regions p. 8
Yusra Kalmoni, Frederick Kwaku Addai, Saviour Kweku Adjenti, Kevin Kofi Adutwum-Ofosu, John Ahenkorah, Bismarck Afedo Hottor, Richard Michael Blay
DOI:10.4103/ijt.ijt_70_18 Context: Relatively scanty literature on autochthonic African Negroid hair morphology provokes research interest for anthropological, forensic, and cosmetic purposes. Aims: This study aimed to contribute basic morphological information on Ghanaian African hairs. Settings and Design: The study was done in selected second-cycle schools in Accra, Ghana, using convenient sampling. Subjects and Methods: Hairs were obtained by pluck method, from 30 males and 30 females aged 15–20 years. Ghanaian African autochthony was established if individuals had two generations of indigenous Ghanaian parentage. Scalp, eyebrow, axilla, and pubic hairs were image captured using a digital light microscope eyepiece connected to a computer. Diameters of hair strands were measured; types of the medulla and the form and shape of the hair roots were studied. Statistical Analysis Used: ANOVA test (SPSS Version 17.0) was used to compare the means of quantitative hair features among the sexes and the four regions of the body studied. Results: Pubic hair shaft was thickest (respective male and female diameters were 100.21 μm, 88.40 μm) and eyebrow hair was thinnest (53.97 and 46.69-μm diameters in males and females, respectively). Axillary and scalp hairs were the closest in diameters with 76.21 and 72.02 μm, respectively, in males and 73.07 and 71.15 μm, respectively, in females. Continuous type medulla was predominant in all hairs, with a trend of percentage occurrence in descending order from the pubic, axilla, eyebrow, and scalp in both sexes. Conclusions: Bodily regional differences in diameter of hair shaft and medullary presence were affirmed.
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zoom.png Tubular hair casts in trichoscopy of hair and scalp disorders p. 14
Mahesh Mathur, Prakash Acharya, Alina Karki, Jyoti Shah, Nisha Kc
DOI:10.4103/ijt.ijt_77_18 Introduction: Hair casts have been reported in a variety of hair and scalp disorders. Trichoscopy allows a quick and noninvasive method for the evaluation of hair and scalp disorders in high magnification. However, the study of hair casts seen in trichoscopy is lacking. Objective: The main objective is to study the occurrence and patterns of tubular hair cast (THC) in different hair and scalp disorders. Patients and Methods: The patients with hair and scalp disorders presenting at the dermatology department of our hospital were evaluated using trichoscopy. Cases of primary parakeratotic disorders and behavioral disorders were excluded. After a detailed history and evaluation of the hair and scalp, histopathology, light microscopic examination, potassium hydroxide examination, and fungal culture were done when necessary. Results: THC was seen in total 21 cases of seven different hair and scalp disorders. Of these, the majority of cases were of discoid lupus erythematosus (DLE) (5/21) and maximum frequency of THCs within a disorder was seen in cases of pemphigus foliaceus (PF) (50%). Proximal casts occurred in 90.47% of cases. Single cast involving two shafts was seen in a case of PF, and two casts within a single shaft were seen in two cases of DLE and one case of alopecia areata. Conclusions: THCs in trichoscopy can be seen in various hair and scalp disorders and their study may help during the diagnosis of those disorders when combined with other trichoscopic features.
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Research on the balance of thiol-disulfide in blood serum in women with telogen effluvium p. 20
Ayşe Akbas, Fadime Kılınç, Sertaç Sener, Akta Akınş, Cemile Bıçer, Orhan Şen
DOI:10.4103/ijt.ijt_78_17 Backgrounds: Telogen effluvium (TE) is the most common reason for hair loss in humans. Although the exact etiopathogenesis of TE has not been revealed clearly and completely, multifactorial etiologies are to be blamed. In recent years, since oxidative stress (OS) has been shown to play an important role in the etiopathogenesis of so many diseases, the effects of OS on several skin diseases are researched and analyzed. Thiols are antioxidant components that include sulfur group, and the balance of thiol-disulfide has an important role in the formation and prevention of OS. This balance is destroyed in many diseases and its effect on TE is not clearly understood yet. Objectives: In this study, we aimed to search the thiol–disulfide balance that could reveal OS in patients with TE. Materials and Methods: Fifty-two patients with TE and control group of 46 persons were included in the study. Native thiol, disulfide, and total thiol levels were evaluated by a new, automatic spectrophotometric method. Disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol rates were calculated. Results: There was no statistical difference between TE patients and control group in terms of native thiol, disulfide, and total thiol levels. Thiol–disulfide balance was fixed and not affected in TE patients.
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zoom.png Serum interleukin-15 is a marker of alopecia areata severity p. 26
Adel Ali Ebrahim, Rehab Mohammed Salem, Asmaa Adel El Fallah, Esraa Taha Younis
DOI:10.4103/ijt.ijt_80_18 Background: Interleukin-15 (IL-15) is a cytokine that is involved in many inflammatory and autoimmune diseases. Although alopecia areata (AA) is an autoimmune disease, serum levels of IL-15 have not been studied well in AA patients. Aim of the Work: We aims at evaluating the serum levels of IL-15 in active AA. Subject and Methods:This case-control study included 40 AA patients and 40 apparently healthy matched controls. Written informed consents were obtained from all the participants. The scalp was examined to assess sites, number, and size of alopecia patches, and the severity of AA lesions was assessed using the Severity of Alopecia Tool score (SALT score) which determine the percentage of hair loss in the scalp. The body was carefully examined to detect any alopecia patches in any hairy area. Nail examination was carried out to detect any nail involvement. Serum IL-15 levels were measured using an ELISA kits. Results: Serum levels of IL-15 in patients were significantly higher than those in the control group (P < 0.001). Serum levels in alopecia totalis were significantly higher than those with one or two patches, and serum levels in patients with both scalp and body involvement were significantly elevated than the levels of patients with either scalp or body involvement. There was a statistically significant positive correlation between SALT score and serum levels of IL-15 (P < 0.001). Conclusion: Serum IL-15 may be a marker of AA severity.
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zoom.png Trigeminal trophic syndrome simulating pityriasis amiantacea p. 31
Luisa Groba Bandeira, Maria Cláudia Alves Luce, Bruno De Castro E Souza, Priscila Kakizaki, Neusa Yuriko Sakai Valente
DOI:10.4103/ijt.ijt_16_18 We report a case of trigeminal trophic syndrome (TTS) on the scalp of a 69-year-old woman. Initially, the diagnosis of pityriasis amiantacea was considered. The review of pathological antecedents and knowledge of TTS were fundamental for the diagnosis of this illness. We performed a brief review on TTS and differential diagnoses.
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zoom.png Nerve sheath myxoma of scalp: A rare site of presentation p. 34
Shakti Kumar Yadav, Sompal Singh, Namrata Sarin, Roshina Naeem, Sonam Kumar Pruthi
DOI:10.4103/ijt.ijt_45_18 Nerve sheath myxoma, a superficial myxoid tumor, was first described in 1969 by Harkin and Reed. Tumor has cytological and histological resemblance with neurothekeoma, another cutaneous myxoid lesion. Nerve sheath myxoma affects individuals of all age groups and equal predilection for both genders with most favored sites being the fingers and knee. Here, we present a case report of nerve sheath myxoma of the scalp, diagnosed and confirmed with histopathology and immunohistochemistry.
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zoom.png Woolly hair nevus type 2: Rare entity p. 38
Farhana Tahseen Taj, Shraddha Kologi
DOI:10.4103/ijt.ijt_28_18 Woolly hair nevus is a rare non hereditary disorder of scalp characterized by curling and kinking of hair. It can present in childhood or adolescent age. Dermoscopy is a useful noninvasive technique to help in the diagnosis of wolly hair nevus. We report a case of woolly hair nevus associated with linear epidermal nevus.
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zoom.png Trichodynia silenced effectively with propranolol p. 41
Piotr Brzezinski, Vijay Zawar, Anca Chiriac
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Role of bronchoscopy in diagnosis of smear-negative pulmonary tuberculosis
Rajendra Prasad, Abhijeet Singh

Egyptian Journal of Bronchology 2019 13(1):1-5

Tuberculosis (TB) remains an important cause of morbidity and mortality in many developing countries including India. Prompt and accurate establishment of diagnosis is one of the essential basic principles of care for persons with TB. Sputum smear microscopy and culture remain the cornerstone of diagnosis but can be negative in a substantial proportion of pulmonary TB patients (multiple smear-negative status or scanty sputum). Bronchoscopy has been proven to be a safe and effective method for those patients with varying diagnostic yields ranging from 30 to 90%. Various specimens are obtained from a fiber-optic bronchoscope such as smear and culture for mycobacteria from the bronchial aspirate or wash, bronchoalveolar lavage fluid, bronchial brushing, postbronchoscopy sputum, transbronchial needle aspiration, and transbronchial biopsy. The diagnostic yield is significantly enhanced when nucleic acid amplification testing is applied to bronchoscopic specimens. The role of bronchoscopy in TB diagnosis is likely to be limited because of availability, cost, and logistical challenges. Future studies are needed to better define the role of the newer diagnostic modalities to improve early TB diagnosis.

Study of cardiopulmonary rehabilitation versus cardiac rehabilitation in patients suffering from coronary artery diseases and chronic obstructive pulmonary disease
Yasser M Mohamed, Hala M Salem, Hazem M Khorshid, Karim H Abdel Fattah

Egyptian Journal of Bronchology 2019 13(1):6-11

Introduction Chronic obstructive pulmonary disease (COPD) and coronary artery disease are common treatable and preventable chronic diseases. Rehabilitation is now considered an important part of the long-term management in both diseases and includes exercise, education, and smoking cessation. Patients and methods This study included 40 patients with COPD and coronary artery disease referred to the cardiac rehabilitation unit at Ain Shams University hospitals. Patients were assessed by clinical assessment, ECG, ECHO, modified Bruce protocol, spirometry, and St George’s Respiratory Questionnaire (SGRQ). Then, patients were divided into two groups: a cardiac rehabilitation group and a cardiopulmonary rehabilitation group. All patients received 8–12 weeks of rehabilitation and were reassessed by spirometry, the modified Bruce protocol, and SGRQ. Results Both groups improved in terms of spirometric parameters (forced expiratory volume in 1 s and forced expiratory volume in 1 s/forced vital capacity), SGRQ, and metabolic equivalents of tasks, but there was a statistically significant in resting heart rate in the cardiopulmonary rehabilitation group. Conclusion The inclusion of upper limb exercise and inspiratory muscles training in pulmonary rehabilitation improves exercise tolerance in patients suffering from both COPD and coronary artery disease compared with cardiac rehabilitation alone.

Cardiac evaluation of patients with chronic obstructive pulmonary disease using echocardiography
Yasser Moustfa Mohammed, Ghada Samir ElShahid, Nehad Mohammed Osman, Nehal Qadry Abd ElHameed

Egyptian Journal of Bronchology 2019 13(1):12-16

Background Chronic obstructive pulmonary disease (COPD) is a significant cause of death. Cardiovascular disease is a significant cause of morbidity and mortality in COPD. Aim We used echocardiography to evaluate cardiac function in patients with COPD and correlated echocardiographic findings with COPD severity. Patients and methods We performed a prospective cross-sectional study on 60 patients with stable COPD who presented to the Abbasia Chest Hospital during the period from November 2016 till August 2017. Spirometry was performed for all participants using American and European Thoracic Society (2005) recommendations. They were classified according to GOLD guidelines (2017) and evaluated by two-dimensional Doppler echocardiography according to American and European Association of Echocardiography ASE recommendations. Results Echocardiographic examination of left ventricular functions revealed no cases of left ventricular systolic dysfunction, but left ventricular diastolic dysfunction was found in ∼25%. Right ventricle dilatation was found in ∼18% of the patients. Tricuspid regurge was seen in ∼75%, with variable grades from mild to severe. Pulmonary hypertension (PH) was found in ∼40% of the patients. It was more prevalent in patients with severe and very severe disease. Correlation between echocardiographic findings and severity of COPD revealed significant positive correlation only with right ventricle size, tricuspid regurgitation, and PH. Conclusion Left ventricular diastolic dysfunction appears to be frequent in patients with COPD, but it is not related to the disease severity. Abnormal right heart changes could be expected. Presence of PH has a linear relationship with COPD severity.

Detection of chronic obstructive pulmonary disease among shisha smokers in the Fayoum Governorate
Assem F El Essawy, Radwa A Elhefny, Randa I Ahmed, Samar A Fouad

Egyptian Journal of Bronchology 2019 13(1):17-28

Background Shisha smoking is a common practice among the population in Arabic countries. Shisha smoking has a negative effect on lung function; it is probably one of the causes for chronic obstructive pulmonary disease (COPD). Objective Detection of COPD among Shisha Smokers in the Fayoum Governorate. Design Prospective study. Setting Fayoum University Hospital in Egypt between 2016 and 2017. Patients and methods Of the 300 participants, 200 were shisha smokers for more than 20 years or their age above 40 years and 100 of them were nonsmoker volunteers. History of smoking was taken from the patients with recording of the COPD assessment score and then general and local examination was done followed by flow volume loop and finally by a chest radiography (posteroanterior view). Statistical analysis: case–control study Coding of the data was done and then entered with SPSS (statistical package for the social sciences) version number 24. After that data was summarized using mean, SD, median, minimum and maximum in the quantitative data with using frequency (count) and relative frequency (percentage) for categorization of data. Results Out of the 300 male patients included in this study 51% has obstructive airway disease and 19% had restrictive airway disease. The mean age was 56.20±10.98 years. Number of hagars smoked by the COPD patients were 10.82±9.88 hagars per day with a duration of smoking of 24.87±12.36 years. Conclusion Shisha smoking increases the risk of COPD and this risk increases with the increase in the duration of smoking and number of hagar smoked was the conclusion of the study.

Forced vital capacity as a primary clinical outcome measure of bronchodilator reversibility in chronic obstructive pulmonary disease
Magdy Mohamed Khalil, Eman Badawy AbdelFattah, Yasmin Yousif Mostafa

Egyptian Journal of Bronchology 2019 13(1):29-34

Background Spirometry is the most reproducible and objective measurement of airflow limitation. The effectiveness of inhaled bronchodilator in individual patients with chronic obstructive pulmonary disease (COPD) is assessed by comparing measurements from pulmonary function tests made before and after administration. Generally forced expiratory volume in one second (FEV1) is the marker used with the global initiative for COPD (Global Initiative for Chronic Obstructive Lung Disease) guidelines. An increase in FEV1 that is both greater than 0.2 l and 12% above the prebronchodilator FEV1 value is considered significant. The aim of this study is to assess forced vital capacity (FVC) as a clinical outcome measure of bronchodilator reversibility in patients with COPD. Patients and methods This was a prospective study conducted on 163 patients with COPD at Suez Chest Hospital during the period from first of October 2016 till the end of March 2017. Patients were diagnosed based on clinical and spirometric criteria, and then reversibility test was done using inhaled short-acting B2-agonist. All patients were subjected to COPD Assessment Test questionnaire. Results Overall, 14.11% of patients had significant increase in FEV1, whereas 54.6% of patients had significant increase in FVC after bronchodilator inhalation. There was a highly significant positive correlation in FEV1 and FVC value before and after bronchodilator inhalation, and there was a highly significant direct correlation between ΔFEV1 and ΔFVC. There was a statistically significant relation between age and COPD Assessment Test score and ΔFVC. Conclusion ΔFEV1 underestimates the true effect of bronchodilator as airway obstruction increases. The addition of ΔFVC to the evaluation will help physicians to better interpret airways reversibility tests, particularly in more severe patients, without adding spirometric maneuvers or measurements. Patients with COPD, even if nonresponders in terms of FEV1, may benefit from bronchodilators because they can breathe at a lower lung volume owing to reduced air-trapping, notwithstanding the fact that they are still flow limited. ΔFVC correlates better than ΔFEV1with the degree of airway obstruction and the clinical status of the patients.

Psychological assessment of patients with bronchial asthma: focus on some predictors of abnormalities
Hend M Esmaeel, Hanan Y Aly

Egyptian Journal of Bronchology 2019 13(1):35-42

Background Bronchial asthma is a common chronic respiratory illness. Psychiatric comorbidity is a neglected zone in the care and management of such important physical disorders as bronchial asthma. Objective The present study targeted a population sample of out-patient asthmatics, aiming at detailed psychocognitive evaluation. Predictors of depression, anxiety, and cognitive impairment were searched for by detailed assessment of patient sociodemographic and disease-related criteria. Patients and methods A total of 50 patients with confirmed asthma diagnosis were recruited and subjected to detailed respiratory and psychiatric evaluation using Mini-Mental State Examination, Beck Depression Inventory-II, and Taylor manifest anxiety scale tests. Results Mild, moderate, and severe depression were diagnosed in 26, 28, and 14% of patients, respectively, whereas mild, moderate, and severe anxiety were revealed in 32, 34, and 20%, respectively. Overall, 54% of the patients showed cognitive impairment. Asthmatic female patients were more common to have depression (P=0.022). The present analysis showed that predictors of cognitive impairment were older age, increasing frequency of hospital admission for asthma in the past year, improper adherence to treatment, and uncontrolled asthma. Meanwhile better education level proved to be protective from abnormal cognitive function. Conclusion There was high prevalence of depression, anxiety, and cognitive dysfunction among asthmatic patients in Sohag University. Improving patient education, patient adherence to treatment, and asthma level control may lessen the chance of cognitive abnormality.

Assessment of lung functions using impulse oscillometry before and after bronchoscopic lung volume reduction with histoacryl gel
Adel M Khattab, Nevine Abd Elfattah, Ayman Farghaly, Alsayyed Hassan

Egyptian Journal of Bronchology 2019 13(1):43-48

Background Many forms of bronchoscopic lung volume reduction were introduced as a treatment for patients with emphysema surpassing the surgical management and its fatality. Biological bronchoscopic lung volume reduction (BBLVR) proved to be a safe and competent solution inducing collapse of the emphysematous segment(s). Impulse oscillometry (IOS) constitutes an effortless but underused surrogate to spirometry in assessment of pulmonary function. Therefore, the aim of this study was to evaluate the use of IOS before and after BBLVR with histoacryl gel in comparison with spirometry among patients with emphysema. Patients and methods A prospective comparative follow-up study was performed at Kobry El-Kobba Military Hospital. A total of 30 patients with radiological evidence of heterogenous emphysema or emphysematous bullae were enrolled during the period from July 2014 to April 2015. BBLVR was accomplished by the instillation of the histoacryl gel into the affected segment(s) using standard technique. Clinical, radiological, and functional assessments were done before and 4 weeks after the procedure. Results After BBLVR, the following outcome was measured: 6-min walk test, partial pressure of O2 in arterial blood, forced expiratory volume in the first second, resistance at 5 Hz, resistance at 20 Hz, and reactance at 5 Hz. They improved with statistical significance among all the patients. There was a negative correlation between forced vital capacity and resistance at 5 Hz in the heterogenous emphysema group (ρ=0.47 and P<0.025); however, the forced expiratory volume at first second showed positive correlation with reactance at 5 Hz in emphysematous bullae group (ρ=0.82 and P<0.023). Conclusion BBLVR with histoacryl gel is associated with improvement in exercise capacity and lung functions. IOS provided comprehensive assessment of the pulmonary functions, which was in good correlation with spirometry.

Evaluation of lung cancer patterns and bronchoscopic presentations in patients admitted to Abbasia Chest Hospital
Farrag A Muhammad, Diab S Haytham, Khalaf A Mostafa

Egyptian Journal of Bronchology 2019 13(1):49-54

Background Lung cancer is the most common cause of cancer-related death worldwide, accounting for more cancer-related deaths compared with colon, breast, and prostate combined. Aim The aim of this work is to detect the predominant bronchoscopic presentations and anatomical sites for all histopathological types of lung cancer. Patients and methods This study was conducted prospectively in the bronchoscopy units in Abbasia Chest Hospital. It included 132 patients suspected clinically and radiologically to have lung cancer and admitted to the hospital during the period from July 2016 to March 2017. Of them, 81 patients were pathologically diagnosed as having primary lung cancer. Statistical analysis χ2 test was used to examine the relationship between the two qualitative variables. Student’s t test was used to assess the statistical significance of the difference between the two study group means. McNamara test was used assess the statistical significance of the difference between a qualitative variable measured twice for the same study group. Results A total of 81 patients (73 males and eight females) with primary lung cancer were included in the study; most of them were in the sixth decade of life. The main anatomical sites of bronchogenic carcinoma were main bronchi and lower lobe bronchi equally (24% each), followed by lower lobe bronchi (20%). Most common macroscopic bronchoscopic presentations of bronchogenic carcinoma were end bronchial lesion (46.91%) followed by external compression (12.35%) and then mucosal infiltration and external compression (9.88%). Conclusion Persistent pulmonary complaints like productive cough, dyspnea, chest pain, and hemoptysis should be investigated immediately. Proper screening and early diagnostic methods should be applied on a large scale to find out suspected patients who at risk to develop lung cancer.

The role of medical thoracoscopy in the management of empyema
Ahmad G El Gazzar, Mohammad A.E El-Mahdy, Gehan F Al Mehy, Asmaa El Desoukey Mohammad

Egyptian Journal of Bronchology 2019 13(1):55-62

Background Empyema thoracis is defined as accumulation of pus in the pleural space. Despite advanced medical diagnostic and therapeutic methods, thoracic empyema remains a common clinical entity and a serious problem all over the world with significant associated morbidity and mortality. Aim The aim of this work was to study the efficacy and safety of medical thoracoscopy (MT) in the management of empyema. Patients and methods This study included 30 inpatients with empyema. Included patients had frank pus on aspiration (turbid purulent fetid fluid) with or without positive Gram stain smear and microbiological culture findings or pH less than 7.20, with signs of sepsis. Patients were managed by MT. MT using rigid thoracoscopy was performed with evacuation of the purulent fluid, visualization of the pleural space, assessment of adhesions and purulent material, forceps adhesiolysis, and irrigation by normal saline with partial debridement of accessible parietal pleural surface. Results The present study included 30 patients with empyema (17 men, 13 women with a mean age of 47.4±14.5 years; range, 18–70 years); 19 (63.3%) patients had free-flowing empyema (by computed tomography/ultrasonography) and 11 (36.7%) patients had multiloculated empyema. The etiology of empyema included pneumonia (parapneumonic effusion) (33.3%), malignancy (23.3%), tuberculosis (6.7%), lung abscess (6.7%), and no cause was identified in nine patients (spontaneous pleural infection) (30%). MT was considered successful without subsequent interventional procedures in 26 of 30 (86.7%) patients, including all patients with free-flowing empyema (19 patients), 63.6% of patients with multiloculated empyema (seven patients), and four (13.3%) patients required surgical intervention (surgical decortication). No procedure-related mortality or chronic morbidity occurred in this study. Conclusion MT is a simple, safe, minimally invasive, and effective modality in the management of empyema.

Evaluation of safety and diagnostic yield of pleural cryobiopsies during thoracoscopy
Mona M Ahmed, Samar H AlSharkawy, Amr M Shoukri, Yousra T AbouBakr

Egyptian Journal of Bronchology 2019 13(1):63-66

Background Biopsies using cryoprobe are now widely used in interventional pulmonology. There are only few data available on the use of cryotechnique through rigid thoracoscopy. Aim The aim of this work was to evaluate the diagnostic yield and safety of pleural cryobiopsies using rigid thoracoscopy. Patients and methods A total of 30 patients with undiagnosed exudative pleural effusion who underwent rigid thoracoscopy were included in our study. Biopsies were obtained from suspicious areas by rigid forceps and cryoprobe. Results A total of 30 patients with undiagnosed exudative pleural effusion have been analyzed. Histopathological results of thoracoscopic pleural biopsies revealed that the most common diagnosis was malignancy (50%), followed by tuberculosis (26.7%). Cryobiopsy specimens were larger than forceps biopsy specimens, with no difference in diagnostic yield (76.7%). Cryotechnique proved to be beneficial in cases of thin highly vascular pleura, allowing easier biopsies with lesser risk of bleeding. In cases of thickened fibrous pleura, there was no difference between both the techniques. Conclusion Pleural cryobiopsies through rigid thoracoscopy is a simple and safe procedure. It has a high diagnostic yield similar to rigid forceps biopsy, and it showed better performance in thin highly vascular pleura where biopsies can be performed with minimal risk of bleeding.


Advanced Pharmaceutical Technology & Research

Nanomedicine in prosthetic dentistry
Upendra Nagaich

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):1-1

Quercetin prevent proteoglycan destruction by inhibits matrix metalloproteinase-9, matrix metalloproteinase-13, a disintegrin and metalloproteinase with thrombospondin motifs-5 expressions on osteoarthritis model rats
Dian Agustina Permatasari, Deantari Karliana, Iskandarsyah Iskandarsyah, Ade Arsianti, Anton Bahtiar

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):2-8

Prior study has shown that Ageratum conyzoides L. extract that containing quercetin has been proved to prevent inflammation and proteoglycan degradation by inhibiting tumor necrosis factor-alpha and matrix metalloproteinase (MMP-9) expression. Target of osteoarthritis (OA) treatment was in the synovial joint that requiring a drug delivery system. The aim of this study was to prove the efficacy of quercetin-loaded lecithin-chitosan nanoparticles on the OA model rats by observed its effect on interleukin (IL-1) β, MMP-9, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-5) expressions. In this study, 70 white male Sprague Dawley rats were divided into 14 groups, 7 groups each for destabilization of medial meniscus (DMM) and monoiodoacetate (MIA)-induced OA. After 28 days from induction, SHAM and negative group received gel base topically; positive group received sodium diclofenac gel; three-dose group received each 0.84, 1.68, 3.36 mg/g quercetin-loaded nanoparticles gel; and A. conyzoides L. group received A. conyzoides L. extract gel. Each group gets treatment until day 70, and then, blood sample was collected for serum analysis; knee joint was isolated and subjected to histology samples treatment. Quercetin-loaded nanoparticle gel dose 1 (0.84 mg/g gel), dose 2 (1.68 mg/g gel), dose 3 (3.36 mg/g), and A. conyzoides L. extract gel could decreased the level of IL-1 β, MMP-9, MMP-13, ADAMTS-5, and increasing color intensity significantly on histopathological observations on DMM and MIA-induced OA.

High mannoronic acid containing alginate affects the differentiation of Wharton’s jelly-derived stem cells to hepatocyte-like cell
Saeed Azandeh, Darioush Bijan Nejad, Vahid Bayati, Foroug Shakoor, Negar Varaa, Bahman Cheraghian

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):9-15

For transplantation of cell into injured tissues, cells should be transferred to the damaged site through an adequate carrier. Nevertheless, the nutrient-limited and hypoxic condition in the carrier can bring about broad cell death. This study set to assess the impact of alginate concentrations on the differentiation and the proliferation of cells encapsulated in alginate hydrogels. Human Wharton's Jelly-derived Mesenchymal Stem Cells (HWJ-MSCs) were encapsulated in two concentrations of alginate hydrogel. Then, the proliferation and the hepatic differentiation were evaluated with an MTT assay and the enzyme-linked immunosorbent assay software and urea production. The results demonstrated that the proliferation of cell and urea production in 1.5% alginate concentration was higher than in 2.5% alginate concentration in the hydrogels of alginate. We deduce that the optimized alginate hydrogel concentration is necessary for achieving comparable cell activities in three-dimensional culture.

The effect of venous caffeine on the prevention of apnea of prematurity in the very preterm infants in the neonatal intensive care unit of Shahid Motahhari Hospital, Urmia, during a year
Zahra Fakoor, Ali Aghayar Makooie, Zahra Joudi, Rasool Gharaaghaji Asl

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):16-19

Due to the importance of prevention of apnea of prematurity in the very preterm infants and the side effects of using methylxanthines in preterm infants, the present study was conducted and aimed at investigating the effects of prophylactic caffeine on the incident of apnea (short-term consequence). This is a clinical–experimental trial, in which the infants were included after receiving written consent from their parents. The infants were randomly divided into two groups, namely, Group A (receive caffeine) and Group B (did not receive caffeine). After sampling of the collected data, the two groups were analyzed using statistical tests using SPSS software 23. Among the 50 infants in the caffeine group and 50 infants in the control group, 1 (2%) and 2 (4%) infants required long-term oxygen, respectively. Three (6%) infants from the caffeine group and 2 (4%) infants from the control group had an intraventricular hemorrhage. Two (4%) infants from the caffeine group and 1 (2%) infant from the control group had a positive patent ductus arteriosus and needed treatment. Among the 50 infants in the caffeine group and 50 infants in the control group, 7 (14%) and 9 (18%) infants had apnea, respectively. According to the Fisher's exact test, there was no significant difference between the incident of apnea in the two groups (P = 0.58). Ten (20%) infants from the caffeine group and 7 (14%) infants from the control group died. The prescription of prophylactic caffeine had no effect on the incident of apnea in the infants. Hence, the use of that should be limited to the preterm infants lower than 1250 g in the prophylactic form.

Proniosomal gel-mediated topical delivery of fluconazole: Development, in vitro characterization, and microbiological evaluation
Amal Saber Mohammed Abu El-Enin, Maha Khalifa Ahmed Khalifa, Aya Mohammed Dawaba, Hamdy Mohammed Dawaba

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):20-26

The aim of this study was to explore the potential of proniosomal gel for topical delivery of fluconazole, an antifungal drug used in fungal infections caused by pathogenic fungi. Fluconazole-loaded proniosomal gels were prepared by the coacervation phase separation method using different nonionic surfactants (spans and tweens). The prepared fluconazole proniosomal gels were evaluated for various parameters such as particle size (PS), drug entrapment efficiency percentage (EE%), and in vitro drug release. The experimental results showed that the EE% for the prepared formulae are acceptable (85.14%–97.66%) and they are nanosized (19.8–50.1 nm) and the diffusion from the gels gave the desired sustaining effect. F4, which was prepared from span 60, tween 80 (1:1), and cholesterol showed highest EE% and gave slow release (40.50% ± 1.50% after 6 h), was subjected to zeta potential (ZP) test, transmission electron microscopy as well as microbiological study. The results showed a well-defined spherical vesicle with sharp boundaries with good physical stability of fluconazole within the prepared gel. Moreover, F4 showed an excellent microbiological activity represented by a greater zone of inhibition (5.3 cm) compared to control gel (fluconazole in 2% hydroxy propyl methyl cellulose (HPMC) gel formula) (4.2 cm) and plain gel with no drug (0 cm) against Candida albicans. This study showed the suitability of the proniosomal gel in attaining the desired sustainment effect for topical delivery of fluconazole for the management of fungal infection. The physical stability study showed that there was no significant change in EE%, PS, and ZP of fluconazole proniosomal gel after storage for 6 months.

The potency of chitosan-Pinus merkusii extract nanoparticle as the antioxidant and anti-caspase 3 on lead acetate-induced nephrotoxicity in rat
Sri Agus Sudjarwo, Koerniasari Eraiko, Giftania Wardani Sudjarwo, Koerniasari

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):27-32

The current study was carried out to evaluate the antioxidant and anti-caspase 3 activity of chitosan-Pinus merkusii nanoparticle in against lead acetate-induced nephrotoxicity in rats. chitosan-P. merkusii nanoparticle was characterized by dynamic light scattering (DLS) and scanning electron microscope (SEM). The male rats were divided into control group (rats were given with distilled water), lead acetate group (rats were injected with lead acetate 15 mg/kg BW i. p), and the treatment group (rats were given the chitosan-P. merkusii nanoparticle 150 mg, 300 mg, 600 mg/kg BW orally and were injected with lead acetate 15 mg/kg BW). The rats blood samples were measured levels of blood urea nitrogen (BUN) and creatinine. The kidney tissues were collected to evaluate the malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx). Histological to evaluate renal damage, and immunohistochemical to analyze the expression of caspase 3. The results showed that DLS showed the size of chitosan-P. merkusii nanoparticle was 165.9 ± 24.18 nm. SEM images of the chitosan-P. merkusii nanoparticles showed an irregular shape and its the rough surface. Administration of lead acetate resulted in a significant increase in levels of the BUN, creatinine, MDA level, caspase 3 expression, and a decrease in SOD and GPx were compared with the control group. Treatment with the chitosan-P. merkusii nanoparticle 600 mg/kg BW significantly decreased the elevated BUN, creatinine, MDA levels, caspase 3 expression and also increase in SOD and GPx as compared to lead acetate group. The lead acetate induced loss of the normal structure of renal cells and necrosis, whereas treated with chitosan-P. merkusii nanoparticle improved renal cell necrosis. This study indicates that chitosan-P. merkusii nanoparticles appeared to be a promising agent for protection against lead-induced nephrotoxicity through increasing antioxidant and inhibiting caspase 3 expression.

Effects of rosuvastatin on metabolic profile: Versatility of dose-dependent effect
Hayder M Al-Kuraishy, Ali I Al-Gareeb

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):33-38

Obesity refers to an excess of body fat content causing metabolic and inflammatory disorders. Therefore, the aim of the present study was to investigate dose-dependent effect of rosuvastatin on the metabolic profile of diet-induced obesity in mice model study. A total number of 40 male Albino Swiss mice were used which divided into Group I: Control group, fed normal diet for 8 weeks (n = 10); Group II: High-fat diet (HFD) group, fed on HFD for 8 weeks (n = 10); Group III: HFD + 20 mg/kg rosuvastatin for 8 weeks (n = 10); and Group IV: HFD +40 mg/kg rosuvastatin for 8 weeks (n = 10). Anthropometric and biochemical parameters were estimated, including fasting blood glucose, lipid profile, fasting insulin, and glucose tolerance test (GTT). Mice on HFD fed showed a significant increase in the insulin resistance, body weight, deterioration of lipid profile and significant reduction in the β-cell function, and insulin sensitivity compared to the control P < 0.05. GTT and blood glucose level were significantly high in HFD fed group compared to the control group P < 0.05. Rosuvastatin in a dose of 40 mg/kg illustrated better effect than 20 mg/kg on the glucometabolic profile P < 0.05. Rosuvastatin may has a potential effect on reduction of glucometabolic changes induced by HFD with significant amelioration of pancreatic β-cell function in dose-dependent manner.

Assessment of the fitness of Cox and parametric regression models of survival distribution for Iranian breast cancer patients’ data
Maryam Mohseny, Reza Shekarriz-Foumani, Parastoo Amiri, Marjan Vejdani, Pezhman Farshidmehr, Hossein Zabihi Mahmoudabadi, Farzaneh Amanpour, Pegah Mohaghegh, Farzad Tajdini, Azadeh Sayarifard, Esmat Davoudi-Monfared

Journal of Advanced Pharmaceutical Technology & Research 2019 10(1):39-44

Factors affecting the time of survival after breast cancer (BC) diagnosis remain unknown. However, some of the prognostic factors have been identified. The aim of this study was to investigate the effects of biologic and socioeconomic factors on long-term survival of BC patients. This was a descriptive chart review and survey of all women with a confirmed diagnosis of BC registered in Shohada-e-Tajrish Cancer Research Center database from March 2004 to March 2015. The checklist of study consisted of biologic, demographic, reproductive, genetic, medical, and therapeutic information of patients. The minimum time of follow-up was 3 years and the maximum was 10 years. We then evaluated possible associations of these variables with BC survival using Cox and parametric regression models of survival analysis. The study population was 1276 BC patients. Their mean survival was 23 (range 1–120) months. Between the parametric models, Weibull regression model demonstrated the lowest Akaike information criterion and thus the best fit, and tumor size, number of lymph nodes, BC stage, educational level, and high-fat diet were significant in this model. Based on our findings, educational level, consumption of fat, and characteristics of tumor at the time of diagnosis (disease stage, tumor size, number of involved lymph nodes) are the most important prognostic factors affecting long-term survival of BC patients. We suggest that future studies assess the efficacy of possible interventions for these factors.