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Παρασκευή 14 Δεκεμβρίου 2018

Indian Journal of Pharmacology (Indian J Pharmacol) 2018 | September-October | Volume 50 | Issue 5

EDITORIAL 

Developing and sustaining India's capacity for preclinical drug discoveryp. 225
David I Lewis, Bhagirath K Patel, B Dinesh Kumar, Bikash Medhi
DOI:10.4103/ijp.IJP_641_18  
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RESEARCH ARTICLESTop

Effect of Vaccinium macrocarpon on MK-801-induced psychosis in micep. 227
Disha Shukla, Rajesh A Maheshwari, Kirti Patel, R Balaraman, Ashim Kumar Sen
DOI:10.4103/ijp.IJP_74_17  
OBJECTIVES: This study was aimed to investigate the effect of aqueous cranberry extract (ACE) on MK-801-induced psychosis in mice.MATERIALS AND METHODS: MK-801-treated mice were administered ACE (1 and 2 g/kg, p.o.) for 14 days. Various behavioral parameters and neurochemical estimations such as dopamine (DA), 5-hydroxytryptamine (5-HT), norepinephrine (NE), gamma-aminobutyric acid (GABA), glutamate, and glycine as well as markers of oxidative stress such as nitrite levels were measured.RESULTS: Psychosis-induced mice showed a significant elevation of immobility time in forced swim test, locomotor activity, and reduction in time of permanency in rota-rod test, escape latency time in Cook's pole test while treatment with ACE showed a significant alteration in above-mentioned behavioral parameters in MK-801-induced psychosis. Moreover, MK-801-induced psychosis in the mice showed a significant increase in DA, 5-HT, and NA levels and decrease in GABA, glutamate, and glycine levels in the brain. In contrast, treatment with ACE at both doses remarkably altered the neurochemical parameters. In addition, ACE-treated mice showed a substantial reduction in acetylcholinesterase, D-amino acid oxidase enzyme activity, and nitrite levels which were elevated by the administration of MK-801. CONCLUSIONS: Treatment with ACE once for 14 days (1 and 2 g/kg) significantly ameliorated the behavioral symptoms in experimentally induced psychosis by virtue of neuromodulation and decreased oxidative stress.
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Efficacy of melatonin on sleep quality after laparoscopic cholecystectomyp. 236
Vaibhav Vij, Divya Dahiya, Lileswar Kaman, Arunanshu Behera
DOI:10.4103/ijp.IJP_250_18  
CONTEXT: Postoperative sleep and circadian rhythm disturbances were associated with prolonged postoperative convalescence, respiratory, and cardiovascular morbidity. Sleep disturbances have been shown to be due to decreased levels of circulating melatonin after surgery. If this sleep pattern and circadian rhythm are recycled, outcome after surgery could be improved. AIMS: The aim of this study was to observe the effect of melatonin on the quality of sleep in patients undergoing laparoscopic cholecystectomy (LC).SUBJECTS AND METHODS: Hundred patients of LC participated in this randomized, placebo-controlled, double-blind, clinical trial. Patients were randomized equally into Group A who received 6 mg melatonin tablets 45 min before sleep for 3 days after surgery and Group B who received placebo. RESULTS: Melatonin usage results in decrease in sleep latency (SL) as compared to placebo (13.6 ± 14.95 vs. 20.10 ± 16.18 min, P = 0.04). There was also increased total sleep duration (TSD) on postoperative day (POD) 1 (P = 0.004) and POD 2 (P = 0.001) in Group A. There was a decrease in daytime naps and night awakenings after surgery in Group A though it was not significant statistically. Subjective assessment of sleep on visual analog scale showed reduced sleep scores (P = 0.001 on POD 1 and 2) and decreased pain (P = 0.02 on POD 1) in Group A. Statistically significant difference was not observed in fatigue or general well-being among groups. CONCLUSIONS: Results in this study could demonstrate that melatonin as a single agent could improve the quality of sleep after LC by decreasing SL and increasing TSD.
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In silico approach to study the metabolism and biological activities of oligomeric proanthocyanidin complexesp. 242
Sankar Jamuna, Ashokkumar Rathinavel, Sakeena Sadullah Mohammed Sadullah, Sivasitambaram Niranjali Devaraj
DOI:10.4103/ijp.IJP_36_17  
OBJECTIVES: Over the past three decades, numerous studies have focused on the biological activities of oligomeric proanthocyanidins (OPCs) in the prevention of many diseases such as neurodegeneration, atherosclerosis, tumorigenesis, and microbial infections. OPC has redox-active metabolites which could modulate the intracellular redox equilibrium to maintain the antioxidant homeostasis. This redox-modulating efficiency of OPC could provide new insights into therapeutic approaches that could reduce the burden of cardiovascular diseases. The main objective of this study was to explore the biological and metabolic activities of OPC using in silicoapproaches. METHODS: To validate the above objective, chemoinformatic tools were used to predict the metabolism of OPC after ingestion, based on both the ligand and structure of the constituent compounds. RESULTS: OPC showed possible sites for Phase I metabolism by cytochrome P450, and the metabolites obtained thereafter may be responsible for its biological activities. Absorption, distribution, metabolism, elimination, and toxicity properties showed efficient absorption, distribution, and metabolism of OPC, without toxicity. CONCLUSION: Thus, from the results obtained, OPC could be strongly recommended as a cardioprotective drug.
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Antidiabetic potential of active fraction obtained from methanolic extract of Ichnocarpus frutescens: A possible herbal remedyp. 251
Mallu Srujana, Ranjana Ramesh, Lakshmi Devi Nanjaiah
DOI:10.4103/ijp.IJP_24_18  
OBJECTIVES: Ichnocarpus frutescens is a common plant used by tribal people and in Ayurveda for its high medicinal value. The purpose of the study was to investigate whether I. frutescens has any persuasive medicinal property to manage diabetes mellitus.MATERIALS AND METHODS: Initially, male albino Wistar rats were given intraperitoneal injection of streptozotocin-nicotinamide to induce diabetes, followed with the administration of active fraction obtained from the methanolic extract of I. frutescens for the next 28 consecutive days. Glibenclamide (25 mg/kg) was used as positive control. RESULTS: According to the results obtained, active fraction at a dose of 50 mg/kg body weight exhibited significant antihyperglycemic activity, which was evident with reduced blood glucose level up to 58.84%. The active fraction also showed improvement in serum lipid profile as well as regeneration of pancreatic β-cells in diabetic rats. Concurrent histopathological studies reinforce the effect of active fraction in healing pancreas, thus justifying the possible mechanism of its antidiabetic activity. CONCLUSION: The results of the present investigation lead credence to the use of I. frutescens in ameliorating the diabetic condition.
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A comparative randomized study on effect of vaginally administered glyceryl trinitrate placebo on cervical ripening prior to induction of labor in overdue pregnanciesp. 260
Özlem Dülger, Bulat Aytek Sik, Yilda Arzu Aba
DOI:10.4103/ijp.IJP_182_18  
OBJECTIVE: The aim of this study is to examine the effectiveness and adverse effects of local glyceryl trinitrate (GTN) application during labor compared with a placebo group. METHODS: The study consisted of 70 pregnant women with overdue pregnancies who presented to the hospital for labor induction between January 2009 and January 2011 in the Obstetrics Clinic of Istanbul Süleymaniye Gynecology and Obstetrics Education and Training Hospital. Vaginal suppositories-containing GTN (36/70) or placebo (34/70) was administered to the participants in a randomized fashion. The placebo and GTN involving vaginal ovules used in the study were prepared in the Pharmacy Department of Istanbul University Faculty of Pharmacy. Maternal effects during labor, rates of normal vaginal and C/S deliveries, the interval between the initial medication and delivery, and amount of total oxytocin used were compared between the GTN and placebo groups. RESULTS: There were no significant differences between the GTN and placebo groups regarding bishop scores, the interval between medication and delivery, delivery types, indications for cesarean section, and complications including hyperstimulation, tachysystole, uterine rupture, placental abruption, and uterine atony (P > 0.05). CONCLUSION: Our results revealed that there were no differences between GTN and placebo regarding their effect on cervical ripening in overdue pregnant women.
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Oxaceprol versus tramadol for knee osteoarthritis: A randomized controlled trialp. 266
Kaushik Mukhopadhyay, Parasar Ghosh, Partha Ghorai, Avijit Hazra, Amal Kanti Das
DOI:10.4103/ijp.IJP_633_16  
OBJECTIVES: To assess efficacy and safety of oxaceprol, a hydroxyproline derivative with putative mechanism of action different from traditional nonsteroidal anti-inflammatory drugs, in symptomatic knee osteoarthritis, in comparison to tramadol. MATERIALS AND METHODS: A parallel group, double-blind, randomized controlled trial was conducted with ambulatory patients over 50 years age suffering from knee osteoarthritis causing pain of at least moderate intensity. Patients were randomized to receive either oxaceprol 200 mg thrice daily or tramadol 50 mg thrice daily for 12 weeks. The primary efficacy variable was symptom relief as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) version 3.1 for pain, stiffness, and physical function. Responder rate (50% pain relief), patient's Clinical Global Impression (CGI), and rescue medication use were other outcomes measured. Vital signs, routine blood counts, tests of hepatorenal function and treatment-emergent adverse events were recorded for safety assessment.RESULTS: From 91 patients recruited, 43 on oxaceprol and 36 on tramadol were evaluable. The WOMAC scores declined significantly from baseline in each arm but remained comparable between groups throughout the 12-week study period. The CGI ratings and 50% responder rates were also comparable at the final visit. Differences in dose up-titration and rescue medication requirements were statistically nonsignificant. So also were the adverse event counts. Compliance was satisfactory in both groups. CONCLUSIONS:Efficacy and tolerability of oxaceprol were comparable to tramadol, and the drug can be considered as an alternative to low-potency opioids in the management of knee osteoarthritis.
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A retrospective analysis of reporting of adverse drug reactions to oncology drugs: An experience from a national center of clinical excellencep. 273
Pramod Kumar Sharma, Arup Kumar Misra, Ajay Gupta, Surjit Singh, Puneet Dhamija, Puneet Pareek
DOI:10.4103/ijp.IJP_544_17  
INTRODUCTION: Adverse drug reaction (ADR) is a public health problem which constitutes one of the leading causes of morbidity and mortality worldwide. In India, only a few studies reported cancer chemotherapy-induced ADRs. The objectives of the present study were to assess the organ system involved, frequency, severity, and preventability of the ADRs occurred. MATERIALS AND METHODS: Data on ADRs of retrospective cohorts were extracted from the filled ADR forms received from the department of radiation oncology. Descriptive statistic was used to summarize and analyze the available data, namely patient demography, causality, severity, and preventability of the event. RESULTS: A total of 191 chemotherapy-induced ADR reports were received from 164 patients during the period March 2015 to August 2017. Almost three-fourth of the ADRs occurred in patients who were receiving regimens involving multiple drugs. Taxanes, alkylating agents, and platinum compounds were the common drug groups involved. The skin (n = 90) was the most frequently involved organ with alopecia and hyperpigmentation as most common manifestations. The severity (Hartwig and Siegel) and preventability scales (Modified Schumock and Thornton) indicated that most reactions were mild (54.45%) in nature and the majority of them were preventable. More than two-third (69%) of the reactions were related "possible" to the suspected drug as determined by the World Health Organization causality assessment. CONCLUSION: Chemotherapy-related ADRs among cancer patients are worrisome. It has a negative impact on patient quality of life and in addition increases cost of therapy. It is found that timely reporting of chemotherapy-related ADRs and having an effective ADR monitoring system in place ensure preventability of the ADRs in many cases. Oncologists, Radiotherapists and Onco-surgeons should be actively involved in ADR reporting (Onco-Pharmacovigilance) and exchange constructive information, update and educate each other about appropriate use of anticancer drugs. Onco-pharmacovigilance is the need of the hour and could be of immense value in reducing morbidity and mortality if practiced with utmost importance.
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Ten units intravenous oxytocin over 2–4 h is as effective as 30 units over 8–12 h in preventing postpartum hemorrhage after cesarean section: A randomized controlled trialp. 279
Maria Cecilia, Reeta Vijayaselvi, Ramandeep Bansal, Latha Lakshmi, Ruby Jose
DOI:10.4103/ijp.IJP_419_18  
OBJECTIVES: Currently, recommended high-dose oxytocin regimen for the prevention of postpartum hemorrhage (PPH) following cesarean delivery (CD) is associated with maternal side effects frequency of which is greater with a higher cumulative dose and rapid administration of oxytocin. Here, we evaluated the efficacy of single-dose intravenous oxytocin over 2–4 h (total = 10 units) with oxytocin maintenance infusion for 8–12 h (total = 30 units) in postoperative CD women for the prevention of PPH. METHODS: The current double-blinded randomized controlled trial was carried out in a tertiary care institute in Southern India. The primary outcome measures included the following: (a) the need for additional uterotonics to control PPH and (b) significant deterioration of vital signs as assessed by pulse rate and blood pressure in the postoperative period. The secondary outcome measures were as follows: (a) significant difference (≥10% between preoperative and postoperative packed cell volume) and (b) need for blood transfusion. RESULTS AND CONCLUSIONS: Two hundred and seventy-one women were randomized into Group A (oxytocin = 10 units; n = 135) and Group B (oxytocin = 30 units; n = 136). Both the groups were comparable with regard to demographic characteristics. There was no difference in any of primary or secondary outcome measures in the two groups. Thus, low-dose oxytocin regimen is as effective as high-dose oxytocin regimen in the prevention of PPH in postoperative CD women.
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DRUG WATCHTop

Rare occurrence of hand-foot syndrome due to paclitaxel: A rare case reportp. 284
Pritam S Kataria, Pradip P Kendre, Apurva A Patel, Nahush Tahiliani, Vijay Bhargav, Honey Parekh
DOI:10.4103/ijp.IJP_547_17  
Hand-foot syndrome (HFS) is a relatively frequent adverse reaction to certain anticancer drugs. HFS is a type of dermatitis which has been most commonly described with 5-fluorouracil and capecitabine. However, HFS with paclitaxel is rare and has been reported sparingly in the literature. A 52-year-old male patient with recurrent carcinoma of the buccal mucosa was started on palliative chemotherapy regimen, injection paclitaxel (175 mg/m2) in combination with injection carboplatin. On post-chemotherapy day 13, the patient started developing pain, dysesthesia followed by bullae formation, and desquamation over palms and soles. Clinically, the patient had Grade 3 HFS characterized by symmetrical, tender skin lesions over the dorsal aspect of palms, and soles with desquamation necessitating interruption of treatment. Therefore, this case has been presented to be cognizant with this rare form of side effect with one of the most commonly used drug in oncology.
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Regional recurrence rate of lymph-node-positive thyroid carcinoma after selective or comprehensive neck dissection

Publication date: Available online 13 December 2018

Source: Oral Oncology

Author(s): Linkai Deng, Yubin Cao, Jie Lin



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A novel anatomy-based five-points eight-line-segments technique for precision subtotal tongue reconstruction: A pilot study

Publication date: February 2019

Source: Oral Oncology, Volume 89

Author(s): Song Fan, Hanqing Zhang, Qunxing Li, Faya Liang, Zhiqiang Bai, Weixiong Chen, Sheng Sun, Peirong Yu, Jinsong Li

Abstract
Objectives

A no-flap design based on actual tongue anatomy has been reported to achieve precise reconstruction, but large carcinologic tongue defects remain extremely challenging to treat. The aim of this pilot study was to explore an anatomy-based flap design for precision subtotal tongue reconstruction.

Material and methods

Thirty-five patients were randomly divided into two groups, a "five-points eight-line-segments" (FIPELS) technique flap design group (18 patients) and a conventional surgery group (17 patients), to undergo subtotal tongue reconstruction. All patients received an anterolateral thigh flap with nerve coaptation to the lingual or glossopharyngeal nerve. Swallowing function, speech intelligibility, and cosmetic results were assessed with a Likert scale, and epicritic and proprioceptive sensitivity and thermosensation of the neotongue were investigated. Outcomes were analyzed, and a p-value < 0.05 was considered significant.

Results

The FIPELS flaps were significantly larger than conventionally designed flaps. All flaps healed uneventfully, except in two patients who presented with partial necrosis. Relative to patients in the conventional group, patients in the FIPELS group showed significantly improved swallowing function (p = 0.043) and cosmetic results (p = 0.017) but not speech intelligibility (p = 0.154). Patients in the two groups recovered comparably in terms of epicritic and proprioceptive sensitivity and thermosensation.

Conclusion

The anatomy-based FIPELS technique is an innovative and effective solution for subtotal tongue reconstruction.



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Mandated wrapping of airway cart instruments: Limited access without the intended safety benefits

Objectives/Hypothesis

Isolated case studies have shown improper sterilization or contamination of equipment from anesthesia carts can lead to transmission of disease and even death. Citing this literature, national accrediting agencies mandated all instruments in the otolaryngology airway carts at San Antonio Military Medical Center be packaged to prevent contamination. This study sought to determine the infection and safety implications of packaged airway cart instruments.

Study Design

Retrospective chart review.

Methods

A review of upper aerodigestive tract procedures, some of which penetrated mucosa, was performed by analyzing 100 patient records during the unpackaged period and 100 during the packaged period. A comparison of infections, deaths, and length of stay in the hospital was included in the analysis. Additionally, a timed simulation to setup a simple group of instruments for an emergency airway situation from both the unpackaged and packaged airway carts was performed using a total of 11 surgical technologists and nurses.

Results

Each group had a total of four airway infections and neither had any deaths. The average length of hospital stay was 0.36 days for the unpackaged period and 0.44 days from the packaged period. None of these variables reached statistical significance. The average time to find and set out the correct instruments for the two groups was 46.6 and 95.5 seconds for the unpackaged and packaged airway carts, respectively (P = .004).

Conclusions

This study suggests individually packaging of instruments used for emergency airway cases may put lives at risk when time matters and fails to decrease the risk of infection.

Level of Evidence

3 Laryngoscope, 2018



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Hypoglossal nerve stimulation in three adults with down syndrome and severe obstructive sleep apnea

We present three adults with Down syndrome and obstructive sleep apnea (OSA) treated with hypoglossal nerve stimulation. The average age of these three males was 37.3 years. All patients had severe OSA on polysomnography. Postimplantation titration sleep studies exhibited residual OSA according to average total apnea‐hypopnea index (AHI), but there were significant reductions (86%–100%) in the titrated AHI at the ideal device setting. Morbidity of the surgery was low, and there was excellent device adherence, with an average of 57.3 hours/week. All patients reported subjective improvements in symptoms, and one patient experienced improved blood sugar control. Laryngoscope, 2018



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Association of epistaxis with atherosclerotic cardiovascular disease

Objectives/Hypothesis

To investigate the association between epistaxis and atherosclerotic cardiovascular disease.

Study Design

Case‐control cohort study.

Methods

This study included patients from the tertiary‐care ear, nose, and throat department at the University Hospital of Zurich between December 1, 2016 and June 1, 2017. We assessed the cardiovascular risk profiles in a group of 41 patients presenting with epistaxis, and a group of 41 matched controls, focusing on a surrogate parameter for atherosclerosis: the carotid intima‐media thickness (CIMT).

Results

With a mean of 1.06 mm (standard deviation [SD] = 0.17), CIMT values were on average 26% higher in epistaxis patients than in their controls, with a mean of 0.84 mm (SD = 0.14; P < .001). Occurrence of severe epistaxis was also associated with lower ankle–brachial index values at 0.96 (SD = 0.12) versus 1.05 (SD = 0.17) (P < .001) and significantly higher QRISK2 relative risks (an algorithm for predicting cardiovascular risk) than found in the control group (1.81, SD = 0.97 vs. 1.35, SD = 0.28; P = .028). A binary logistic regression model, adjusted for possible confounders, showed an odds ratio of 2.5 for the occurrence of epistaxis per increase in CIMT of 0.1 mm in the study population (95% confidence interval: 1.56‐4.11; P < .001).

Conclusions

The occurrence of severe epistaxis was shown to be closely associated with the prevalence of atherosclerotic cardiovascular disease. Accordingly, patients affected by epistaxis should be regarded as at an elevated cardiovascular risk, which indicates the need for appropriate further medical assessment and preventive measures.

Level of Evidence

3b

Trial registration

Clinical trials NCT03092973 Laryngoscope, 2018



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Role of Antibiotics in Post-Tonsillectomy Morbidities; A Systematic Review

Publication date: Available online 13 December 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Amr Ossama Abdelhamid, Tamer Shoukry Sobhy, Hazem Mounir El-Mehairy, Ossama Hamid

Abstract
Objective

To evaluate the role of postoperative antibiotics on post-tonsillectomy morbidities.

Study Design

Systematic Review.

Methods

Published papers and electronic databases (Medline, Web of Science, Embase) were searched from January 1985 up to March 2016 using the following key words in different combinations; Tonsil; Tonsillectomy; Post-tonsillectomy; Adenotonsillectomy; Antibiotics; Post-tonsillectomy morbidity; Bleeding; Secondary Hemorrhage. Twelve randomized control clinical trials fit the inclusion criteria and were included in the meta-analysis. We evaluated 5 outcomes, hemorrhage, return to normal diet, return to normal activities, fever and pain.

Results

As regards secondary hemorrhage pooled analysis of 1397 patients revealed a relative risk (risk ratio, RR) of 1.052 with a 95% confidence interval (95% CI) of 0.739 to 1.497 (P-value, 0.779). As for return to normal diet pooled analysis of 527 patients showed a standardized mean difference (SMD) of -0.058 day with 95% CI of -0.233 to 0.118 (P-value, 0.518). As for return to normal activities pooled analysis of 257 patients showed a SMD of -0.014 day with a 95% CI of -0.258 to 0.230 (P-value, 0.908). As for Fever pooled analysis of 656 patients revealed a relative risk of 1.265 with 95% CI of 0.982 to 1.629 (P-value, 0.068). Finally for the postoperative pain due to the variability in the parameters used to assess the pain following tonsillectomy, we could not perform meta-analysis for this outcome.

Conclusion

The results of this study fail to support clear evidence to use routinely post-operative antibiotics to reduce post-tonsillectomy morbidities.



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CD4+ T cells induce productions of IL-5 and IL-13 through MHCII on ILC2s in a murine model of allergic rhinitis

Publication date: Available online 13 December 2018

Source: Auris Nasus Larynx

Author(s): Lin Lin, Zheng Chen, Fei Dai, Jin-Jin Wei, Xin-Yue Tang, Guang-Bin Sun

Abstract
Objective

CD4+ T cells play an important role not only in the induction of allergy but also in allergic inflammation. Group 2 innate lymphoid cells (ILC2s) also mediate type 2 immune responses in allergic rhinitis (AR). However, the relationships between CD4+ T cells and ILC2s in allergic condition are currently not well defined. The study aimed to evaluate the potential influences of CD4+ T cells on ILC2s in the murine model of AR.

Methods

A murine model of AR was established using ovalbumin (OVA), and OVA-induced ILC2s were sorted and purified from the mouse nasal-associated lymphoid tissue (NALT), and cultured in vitro. Then, the expression of major histocompatibility complex class II (MHCII) on ILC2s was examined. CD4+ T cells were separated from AR mice peripheral blood mononuclear cells (PBMCs). After that, productions of IL-5 and IL-13 on ILC2s cultures were assessed when CD4+ T cells or plus anti-MHCII antibody or anti-CD4 antibody were administered into the cultures. Finally, we adoptively transferred ILC2s alone or ILC2s plus anti-MHCII antibody to the murine model of AR to investigate their roles in the nasal allergic inflammation.

Results

We showed that ILC2s could be induced by OVA in the mouse NALT. The number and percentage of ILC2s in AR mice were increased. MHCII was expressed on ILC2s, and its protein and mRNA were all enhanced in allergic condition. IL-5 and IL-13 proteins and mRNAs were elevated after CD4+ T cells administration, and were reduced after these cells plus anti-MHCII antibody or anti-CD4 antibody application. Numbers of sneezing and nasal rubbing as well as counts of eosinophils in nasal lavage fluid (NLF) were all enhanced after the adoptive transfer of ILC2s when compared to AR mice. IL-5 and IL-13 in the NLF of allergic mice were also increased in comparison with AR group. However, above parameters were all decreased after the transfer of ILC2s plus anti-MHCII antibody versus AR mice or ILC2s-treated ones.

Conclusion

These findings show that CD4+ T cells induce productions of IL-5 and IL-13 through MHCII on ILC2s in AR mice models.



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The differences in the expression of fractalkine and its receptor in conditions of tonsillar hypertrophy and chronic tonsillitis

Publication date: Available online 13 December 2018

Source: Auris Nasus Larynx

Author(s): Elif Koclu Hetemoglu, Seda Turkoglu Babakurban, Yunus Kasım Terzi, Feride Iffet Sahin, Selim Sermed Erbek

Abstract
Objective

Fractalkine, member of chemokine family, is involved in many inflammatory processes in the human body. The aim of this study is to compare expression levels of fractalkine ligand and its receptor in chronic tonsillitis and hypertrophic tonsil samples.

Methods

The study was conducted at Baskent University Departments of Otorhinolaryngology and Medical Genetics. It is designed as a prospective, non-randomized, controlled clinical study. Total 97 samples, obtained from adenotonsillectomy due to chronic tonsillitis or tonsillar hypertrophy, were participated in the study. Fractalkine and its receptor expression levels were determined and comparison was made between the tissue groups. c.839C > T (T280 M) polymorphism of fractalkine receptor was analyzed, then relationship between polymorphism and the expression level of fractalkine receptor was investigated.

Results

Fractalkine receptor expression was significantly higher in the hypertrophic tonsil group than chronic tonsillitis group (p < 0.05).

Conclusion

Fractalkine, member of chemokine family, and its receptor may play role in preventing chronic-recurrent tonsillitis.



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A novel partner of TFE3 in the Xp11 translocation renal cell carcinoma: c linicopathological analyses and detection of EWSR1 - TFE3 fusion

Abstract

The renal cell carcinomas associated with Xp11 translocations (Xp11 translocation RCCs) harbor gene fusions involving TFE3, a member of the microphthalmia-associated transcription factor (MiTF) family. In the present study, we identified a novel partner of TFE3, Ewing sarcoma breakpoint region 1 (EWSR1), in an Xp11 translocation RCC. A 57-year-old Japanese woman without special disease history was referred to us for treatment of an RCC. The resected tumor displayed an alveolar growth pattern with high-grade nuclei. The tumor was diffusely positive for TFE3 and cathepsin K. Anchored multiplex PCR revealed a novel fusion, EWSR1-TFE3. Fluorescent in situ hybridization analysis demonstrated the rearrangements of EWSR1 and TFE3. RT-PCR analysis confirmed the chimeric transcript. No neoplasm with EWSR1-TFE3 has been reported so far, in any organ. The results will expand the genomic spectrums of Xp11 translocation RCCs and contribute to better understanding of the roles of the MiTF family in the oncogenic process.



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Rational combination of cancer immunotherapy in melanoma

Abstract

The recent advances in cancer immunotherapy with unprecedented success in therapy of advanced melanoma represent a turning point in the landscape of melanoma treatment. Given the complexity of activation of immunological system and the physiologic multifactorial homeostatic mechanisms controlling immune responses, combinatorial strategies are eagerly needed in melanoma therapy. Nevertheless, rational selection of immunotherapy combinations should be more biomarker-guided, including not only the cancer immunogram, PD-L1 expression, interferon gene expression signature, mutational burden, and tumor infiltration by CD8+ T cells but also intratumoral T cell exhaustion and microbiota composition. In this review, we summarize the rationale to develop combination treatment strategies in melanoma and discuss biological background that could help to design new combinations in order to improve patients' outcome.



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Πέμπτη 13 Δεκεμβρίου 2018

Journal of Current Research in Scientific Medicine (J Curr Res Sci Med) 2018 | July-December | Volume 4 | Issue 2

EDITORIAL 

Hemophagocytic lymphohistiocytosis: A cross talk between clinics and laboratory Highly accessed articlep. 73
Somanath Padhi, Rajlaxmi Sarangi
DOI:10.4103/jcrsm.jcrsm_29_18  
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REVIEW ARTICLETop

Diabetes mellitus: Can retinopathy be far behind? Highly accessed articlep. 78
Renuka Srinivasan
DOI:10.4103/jcrsm.jcrsm_35_18  
Diabetic retinopathy (DR), also known as diabetic eye disease, is one of the most common complications of diabetes mellitus and most common cause of low vision and blindness in India. It is a progressive condition with microvascular alterations that lead to retinal ischemia and macular edema. A number of recent advances have emerged in the diagnosis and management of DR. These advances could provide the means to develop major public health strategies to prevent DR and better management of diabetic retinopathy.
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ORIGINAL ARTICLESTop

A study of blood lead levels in young myocardial infarction patients Highly accessed articlep. 81
Ramesh Ayil Nagarajan, Sudhagar Mookkappan, Mark Christopher Arokiaraj, Aneesh Basheer, Nayyar Iqbal
DOI:10.4103/jcrsm.jcrsm_26_18  
Background: The toxicity due to lead is a widely researched sphere of public interest. Positive associations have been identified between lead exposure and coronary heart disease and cardiac rhythm disturbance. This study has been undertaken in general population to determine whether the blood lead level has any role in cardiovascular disease. Aims and Objectives: To estimate the blood levels in young patients with Myocardial Infarction and compare with the older patients. Settings and Design: A descriptive cross-sectional study was conducted among 100 patients with Myocardial Infarction [MI] admitted in a private medical college over a Study Period of 12 months categorized into 2 groups of 50 each based on age <45 yrs and >45 yrs. Materials and Methods: Patients with ECG changes suggestive of Myocardial Infarction and elevated CKMB and Troponin I were included and patients with other than the conventional risk factors were excluded. Patients were further investigated for complete blood count, fasting lipid profile, serum electrolytes, 2D echocardiograph, CK-MB, Troponin I and blood lead levels. Results: The prevalence of MI was 94% and 8% in men and women of the younger group whereas 74% in men and slightly higher percentage of 26% in women of the older group. The mean blood lead levels was 8.392 mg/dl with a standard deviation of 4.5 mg/dl among younger patients as compared to mean of 15.048 mg/dl with standard deviation of 2.5 mg/dl indicating a significant increase in blood lead levels as the age progresses, though the lead levels were in normal range. Conclusion:The study revealed a significant correlation of serum lead concentration with progression of age, though no such correlation was found with Myocardial Infarction. However further studies with healthy participants, larger sample size and data in regards to specific occupation, life style and geographic location can yield significant results to attribute serum lead as a risk factor for developing cardiovascular disease.
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The incidence and prevalence of adverse drug reactions among medical inpatients in a Nigerian University Teaching Hospitalp. 86
Peter Ehizokhale Akhideno, Olumuyiwa John Fasipe, Ambrose Ohumagho Isah
DOI:10.4103/jcrsm.jcrsm_20_18  
Aim: Evaluating the incidence, prevalence, and pattern of adverse drug reactions (ADRs) with the extent to which they influence cost of healthcare is often informative and useful in patients' management, policymaking and safety considerations. Methods: The patients admitted into the internal medicine wards of a university teaching hospital, South-South Nigeria over a 9-month period from December 2013 to August 2014 were prospectively recruited for the study and followed up till discharge. Results: Five hundred and seven patients were evaluated during the study, out of which 269 (53.1%) of them were males and 238 (46.9%) were females. The mean age of the study population was 48.9 ± 17.8 years (median of 46 years). ADRs had an incidence of 6.5%, while its prevalence rate was 10.1%. The cost of treating ADR was ₦ 161668.00 ($1243.60), equivalent to 1.9% of the total cost of all medications used by patients during admission. The case fatality rate for ADRs was 7.8%, while ADR-related mortality rate was 0.8%. The most frequently affected body systems were the central nervous system and the gastrointestinal system corresponding to insulin use (causing neuroglycopenic symptoms) and nonsteroidal anti-inflammatory drugs (NSAIDs) use (causing NSAID-induced gastroenteritis/GIT bleeding) respectively. Conclusions: The incidence and prevalence of ADRs were clinically significant among these medical inpatients. In this study, ADRs increase patients morbidity, mortality, cost of health care, and duration of hospital stay as it has been shown by previous studies. Insulin caused the highest number of ADRs, suggesting the need for individual diabetic patients to acquire and learn the appropriate regular use of glucometers.
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Impact of taking thyroxine with herbal brews Highly accessed articlep. 94
George Thomas, Anulekha Mary John, Jibily Joy, Sherin Sarah Mathew, Alice David
DOI:10.4103/jcrsm.jcrsm_32_18  
Background/Objectives: Herbal brews other than tea/coffee are becoming popular. We observed that these interfered with absorption of thyroxine. Since no prior studies have examined this, we sought to estimate this interaction effect, if any. Materials and Methods: This study was conducted among outpatients of a tertiary care hospital in India. Patients on thyroxine replacement were interviewed regarding the drink used with thyroxine. Various herbal brews used were compared against plain water. Thyroid-stimulating hormone was measured and compared. Results: Total of 121 patients fulfilled the inclusion and exclusion criteria, and 69 (57.0%) patients among them took thyroxine with a herbal brew. Various herbal products included cutch-tree (Karingali) 26 (37.7%), herbal mixture (Dahashamini) 28 (40.6%), and others 15 (21.7%). Risk of not achieving euthyroidism with any herbal brew was 7.6 times high (odds ratio [OR] 7·6 with 95% confidence interval [CI]: 3·1–18·5) as against plain water and was the highest for cutch, OR 12.4 with 95% CI: 4.0–38.0. Conclusions: Several patients take thyroxine with water brewed with herbal products. Effectiveness of thyroxine was greatly reduced when taken with herbal brews.
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Comparison of four different methods of smear preparation for Gram staining of positively flagged automated blood culture bottlesp. 98
Jyoti Nain, R Deepashree, Pratibha Tamang, Prasanna Bhat, Suman Prakash, R Sneha, T Kalpana, G Anitha, Apurba Sankar Sastry
DOI:10.4103/jcrsm.jcrsm_34_18  
Introduction: Gram staining of smears prepared from positively flagged blood culture bottles plays a vital role because its accurate interpretation helps the clinicians to modify empirical therapy as well as to perform the direct susceptibility test, which reduces the turnaround time by 24 h to initiate pathogen-directed antimicrobial therapy. However, the interpretation of direct Gram stain from blood culture bottles has always been at risk of errors in interpreting. Aim: The present study was conducted to find the agreement between the blood culture broth Gram stain finding of four different methods (conventional, water wash, blood film, and drop and rest) of smear preparation with the culture smear Gram stain result and also to compare the quantity of charcoal and resin particles present in the Gram stained smears made from four different smear preparation methods. Method and Result: Smears were made from 500 positively flagged automated blood culture bottles using the four different methods and then compared for agreement with the culture smear Gram stain using kappa statistics and were found to be maximum for the blood film method (0.637), followed by drop and rest (0.570), water-wash (0.496), and conventional method (0.475). The 3+ grading for resin/charcoal was found in 184 (36.80%) smears, 169 (33.80%), 93 (18.60%), and 26 (5.20%) smears prepared by water-wash, conventional, drop and rest, and blood film method, respectively. The interference caused by resin/charcoal was maximum when smears were prepared by the conventional method resulting in high inaccurate interpretation. Conclusion: In this study, the agreement between direct smear preparation methods from positively flagged blood culture broth with the culture smear Gram stain was found to be maximum for the blood film method, followed by drop and rest, waterwash, and conventional method.It was also observed that the least amount of resin/charcoal was encountered when the direct smears were prepared using the blood film method.Hence, we found that the blood film method helps in interpreting the Gram stained smears from positively flagged blood culture broth more accurately compared to other methods.
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Effect of regular treatment, follow-up, and lifestyle practices in diabetic patients with ocular manifestations attending a tertiary care hospital in Puducherry, Indiap. 104
Nivedha S Raman, Amod Hansdak
DOI:10.4103/jcrsm.jcrsm_33_18  
Background: The last few decades have witnessed the growth of diabetes mellitus which is affecting all sections of the society. Complications of diabetes and its management present a still further challenge to health care providers. Methods: A hospital-based cross-sectional study was conducted at Pondicherry Institute of Medical Sciences, India, to find out the treatment and follow-up of patients with diabetes mellitus and also to estimate ocular manifestations among the study subjects. Results: Regular treatment was found among 80% while regular follow-up was seen in 55.7% of the diabetic patients. Two-thirds of the patients were on oral hypoglycemic agents only. 18.6% of the patients tested their blood glucose levels once a month. Visit to an ophthalmologist was made in the last 12 months by 32.9% of them. Ocular manifestations were present in both vegetarians 80% and non-vegetarians 76% respectively. Diabetics practicing sedentary lifestyle had more ocular manifestations 87% as compared to 62.5% in those who did not exercise. Ocular manifestation was also higher among those with elevated blood glucose levels 74.4% in comparison to 61.3% among those with normal blood glucose levels.Conclusion: This study highlights the importance of regular treatment and follow-up by patients with diabetes in relation to development of ocular manifestations. Exercise in diabetes is a key factor in delaying complications such as retinopathy.
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CASE REPORTSTop

Posterior reversible encephalopathy syndromep. 109
Neha Sivaguru, KM Indira, K Pradeep, L Gopinath, Nayyar Iqbal
DOI:10.4103/jcrsm.jcrsm_36_18  
Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiographical syndrome of varying etiologies. It is characterized by headache, confusion, seizures, visual loss, and raised blood pressure along with magnetic resonance imaging abnormalities. It is associated with a number of conditions such as hypertension, eclampsia, vasculitis, chemotherapeutic drugs, and postpartum state. We report the case of a 28-year-old female who developed PRES on her 8th day of postpartum along with subarachnoid hemorrhage.
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A case of successful management of perioperative pulmonary embolismp. 112
Sivakumar Segaran, BT Arish, Athmanathan Mohan, Vikasini Jayaraman, Abinaya Ramachandran
DOI:10.4103/jcrsm.jcrsm_17_18  
Acute pulmonary embolism (PE) is a relatively common complication after major orthopedic surgeries with a high mortality rate. We present a case of L4–L5 disc prolapse with radiculopathy posted for spinal instrumentation and fusion surgery who developed PE perioperatively. It was diagnosed initially with point-of-care echocardiography and confirmed with computed tomography pulmonary angiography. The patient was thrombolyzed with streptokinase, following which she developed bleeding from the surgical site which was managed conservatively with blood transfusions. The patient recovered well and discharged after a week. The management of PE tests the skills of the anesthetist with respect to detection and rapid hemodynamic management.
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Bilateral absence of third and fourth lumbricals: A case report with clinico-evolutionary insightp. 116
NA Priyadharshini, V Dinesh Kumar, R Rajprasath
DOI:10.4103/jcrsm.jcrsm_16_18  
Lumbricals are wormlike, intrinsic muscle of the hand. During routine dissection of a male cadaver of age approximately ranging between 50 and 55 years, the absence of third and fourth lumbricals on both the palm was observed. First and second lumbricals showed no anatomical variation. Other muscles of hypothenar eminence supplied by deep branch of ulnar nerve which also supplies the third and fourth lumbricals were normal. Lumbricals are principle extensors of interphalangeal joint, and its role in flexion of metacarpophalangeal joint is meager. Variability in the presence of medial two lumbricals has evolutionary correlation and also shows its minimal role in the extension of interphalangeal joint of its respective digits. Henceforth, knowledge of absence of lumbricals is crucial for surgeons while planning for hand surgery.
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A case of perioperative myocardial infarction leading to asystole: An anesthesiologist's nightmarep. 119
Sivakumar Segaran, Mamie Zachariah Ninan, RV Ranjan, Leenu Grace Ninan, Vikasini Raman
DOI:10.4103/jcrsm.jcrsm_14_18  
Perioperative myocardial infarction (PMI) in patients without a prior history of coronary artery disease is quite rare. Diagnosing PMI is also quite challenging because of a myriad of events mimicking MI during the perioperative period. we are reporting of PMI leading to cardiac arrest which was successfully resuscitated with the help of a multidisciplinary team. Cardiologist opinion was obtained, and angiogram was done which showed block in left anterior descending artery for which he was stented with drug-eluting stent and discharged a week after with full neurological recovery. The mechanism for triggering PMI in our case is quite inconclusive.
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LETTERS TO EDITORTop

Potential factors influencing the effectiveness of feedback in medical educationp. 122
Saurabh Rambiharilal Shrivastava, Prateek Saurabh Shrivastava
DOI:10.4103/jcrsm.jcrsm_24_18  
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Expertise reversal effect: What every faculty need to know while designing a lecture?p. 124
V Dinesh Kumar
DOI:10.4103/jcrsm.jcrsm_28_18  
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Making poster presentations more effective: Closing the gap between expectation and realityp. 126
V Dinesh Kumar
DOI:10.4103/jcrsm.jcrsm_15_18  
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Reply to "Letter to editor" written in response to "Perspectives on poster as a presentation mode in conferences"p. 128
Himel Mondal, Shaikat Mondal
DOI:10.4103/jcrsm.jcrsm_18_18  
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