Search results for: lung inflammation

Authors: Shreya Ghosh, Akansha Garg, Chayanika Kala, Ashwani Kumar Thakur

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Background: Granuloma formation is one of the characteristic features of tuberculosis. Besides, chronic inflammation underlying tuberculosis is often indicated by an increase in the concentration of serum amyloid A (SAA) protein. The connection between tuberculosis and SAA-driven secondary amyloidosis is well documented. However, SAA-derived amyloid deposition start sites are not well understood in tuberculosis and other chronic inflammatory conditions. It was hypothesized that granuloma could be a potential site for an amyloid deposition because both SAA protein and proteases that cleave SAA into aggregation-prone fragments are reported to be present in the granuloma. Here the authors have shown the presence of SAA-derived amyloid deposits in the granuloma of tuberculosis patients. Methodology: Over a period of two years, tuberculosis patients were screened, and biopsies were collected from the affected organs of the patients. The gold standard, Congo red dye staining, was used to identify amyloid deposits in the tissue sections of tuberculosis patients containing granulomatous structure. Results: 11 out of 150 FFPE biopsy specimens of tuberculosis patients showed eosinophilic hyaline-rich deposits surrounding granuloma. Upon Congo red staining, these deposits exhibited characteristic apple-green birefringence under polarized light, confirming amyloid deposits. Further, upon immunohistochemical staining with anti-SAA, the amyloid enriched areas showed positive immunoreactivity. Conclusion: In this pilot study, we have shown that granuloma can be a potential site for serum amyloid A-derived amyloid formation in tuberculosis patients. Moreover, the presence of amyloid gave significant cues that granuloma might be a probable amyloid deposition start in tuberculosis patients. This study will set a stage to expand the clinical and fundamental research in the understanding of amyloid formation in granuloma underlying tuberculosis and chronic inflammatory conditions.

Keywords: amyloid, granuloma, periphery, serum amyloid A, tuberculosis

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Authors: Yi-Hui Lai, Chih-Hsiang Yang, Li-Chung Hsu

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The inflammasome is a protein complex that modulates caspase-1 activity, resulting in proteolytic cleavage of proinflammatory cytokines such as IL-1β and IL-18, into their bioactive forms. It has been shown that the inflammasomes play a crucial role in the clearance of pathogenic infection and tissue repair. However, dysregulated inflammasome activation contributes to a wide range of human diseases such as cancers and auto-inflammatory diseases. Yet, regulation of NLRP3 inflammasome activation remains largely unknown. We discovered a novel DEAD box protein, whose biological function has not been reported, not only negatively regulates NLRP3 inflammasome activation by interfering NLRP3 inflammasome assembly and cellular localization but also mitigate pyroptosis upon pathogen evasion. The DEAD-box protein is the first DEAD-box protein gets involved in modulation of the inflammasome activation. In our study, we found that caspase-1 activation and mature IL-1β production were largely enhanced upon LPS challenge in the DEAD box-containing protein- deleted THP-1 macrophages and bone marrow-derived macrophages (BMDMs). In addition, this DEAD box-containing protein migrates from the nucleus to the cytoplasm upon LPS stimulation, which is required for its inhibitory role in NLRP3 inflammasome activation. The DEAD box-containing protein specifically interacted with the LRR motif of NLRP3 via its DEAD domain. Furthermore, due to the crucial role of the NLRP3 LRR domain in the recruitment of NLRP3 to mitochondria and binding to its adaptor ASC, we found that the interaction of NLRP3 and ASC was downregulated in the presence of the DEAD box-containing protein. In addition to the mechanical study, we also found that this DEAD box protein protects host cells from inflammasome-triggered cell death in response to broad-ranging pathogens such as Candida albicans, Streptococcus pneumoniae, etc., involved in nosocomial infections and severe fever shock. Collectively, our results suggest that this novel DEAD box molecule might be a key therapeutic strategy for various infectious diseases.

Keywords: inflammasome, inflammation, innate immunity, pyroptosis

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Authors: Khalid Al Saleh, Najlaa AlSayed

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Background: Palliative care is changing from just ‘end of life care’ to care delivered earlier in the disease course. Metanalysis showed that Palliative Performance Scale (PPS) is associated with increased length of survival. The Palliative Care Center (PCC) in Kuwait is the only stand-alone center in Eastern Mediterranean Region with a capacity of 92 beds. We compared clinical characteristics between patients referred from the Specialized Cancer Center and general hospitals in Kuwait to PCC. Method: A cross Sectional survey was conducted since the opening of PCC in January 2011 to June 2013. Patients’ data on demographics, type of the cancer, PPS score and referring hospital were collected and analyzed. Results: Total number of the patients was 142. Mean age was 61.05±14.79 years, 66 patients (47.1%) were males and 74 (52.9%) were females. The most common cancers in males were lung (n=18, 27.3%) followed by head and neck cancers (n=8, 12.1%) and brain tumors (n=7, 10.6%) while in females, the most common cancers were breast cancer (n=12, 16.7%) followed by ovarian cancer (n=10, 13.9%) and Cancer Colon (n=8, 11.1%). Patients with PPS score 30% were 27.9% (n=39), 40% in 40.7% (n=57), and 50% in 17.1% (n=24) respectively. Patients referred from the Specialized Cancer Center had significantly higher portion of patients with PPS score > 30% (73.4%, n=94), compared to patients coming from general hospitals (33.3%, n=4), P value= 0.007. Conclusion: There is significant difference in PPS scores between patients referred from the Specialized Cancer Center compared to patients referred from general hospitals. We encourage that all cancer patients should be treated in Specialized Cancer Centers and earlier involvement of Palliative Care Centers to achieve better survival. Training workshops are needed for health care professionals working in general hospitals to raise awareness about earlier referral of patients to palliative care services.

Keywords: palliative care, kuwait, performance scale differences, pps score, specialized hospitals

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Authors: Ying Zhu, Ning Wu, Hai-Dong Huang, Yu-Chao Dong, Qin-Ying Sun, Wei Zhang, Qin Wang, Qiang Li

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Background and study aims: Tracheobronchopathia osteochondroplastica (TO) is an uncommon disease of the tracheobronchial system that leads to narrowing of the airway lumen from cartilaginous and/or osseous submucosal nodules. The aim of this study is to perform a detailed review of this rare disease in a large cohort of patients with TO proven by fiberoptic bronchoscopy from China. Patients and Methods: Retrospective chart review was performed on 41,600 patients who underwent bronchoscopy in the Department of Respiratory Medicine of Changhai Hospital between January 2005 and December 2012. Cases of TO were identified based on characteristic features during bronchoscopic examination. Results: 22 cases of bronchoscopic TO were identified. Among whom one-half were male and the mean age was 47.45 ±10.91 years old. The most frequent symptoms at presentation were chronic cough (n=14) and increased sputum production (n=10). Radiographic abnormalities were observed in 3/18 patients and findings on computed tomography consistent with TO such as beaded intraluminal calcifications and/or increased luminal thickenings were observed in 18/22 patients. Patients were classified into the following categories based on the severity of bronchoscopic findings: Stage I (n=2), Stage II (n=6) and Stage III(n=14). The result that bronchoscopic improvement was observed in 2 patients administered with inhaled corticosteroids suggested that resolution of this disease is possible. Conclusions: TO is a benign disease with slow progression, which could be roughly divided into 3 stages on the basis of the characteristic endoscopic features and histopathologic findings. Chronic inflammation was thought to be more important than the other existing plausible hypotheses in the course of TO. Inhaled corticosteroids might have some impact on patients at Stage I/II.

Keywords: airway obstruction, bronchoscopy, etiology, Tracheobronchopathia osteochondroplastica (TO), treatment

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Authors: Huashan Tai, Chien-Hui Lung

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Nowadays people use massive fossil fuels which not only cause environmental impacts and global climate change, but also cause the depletion of non-renewable energy such as coal and oil. Bioenergy is currently the most widely used renewable energy, and agricultural waste is one of the main raw materials for bioenergy. In this study, we use orange peel residue, which is easier to collect from agricultural waste to produce bio-coal by torrefaction. The orange peel residue (with 25 to 30% moisture) was treated by torrefaction, and the experiments were conducted with initial temperature at room temperature (approximately at 25° C), with heating rates of 10, 30, and 50°C / min, with terminal temperatures at 150, 200, 250, 300, 350℃, and with residence time of 10, 20, and 30 minutes. The results revealed that the heating value, ash content and energy densification ratio of the solid products after torrefaction are in direct proportion to terminal temperatures and residence time, and are inversely proportional to heating rates. The moisture content, solid mass yield, energy yield, and volumetric energy density of the solid products after torrefaction are inversely proportional to terminal temperatures and residence time, and are in direct proportion to heating rates. In conclusion, we found that the heating values of the solid products were 1.3 times higher than those of the raw orange peels before torrefaction, and the volumetric energy densities were increased by 1.45 times under operating parameters with terminal temperature at 250°C, residence time of 10 minutes, and heating rate of 10°C / min of torrefaction. The results indicated that the residue of orange peel treated by torrefaction improved its energy density and fuel properties, and became more suitable for bio-fuel applications.

Keywords: biomass energy, orange, torrefaction

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Authors: Ramasamy Tamizhselvi, Leema George, Madhav Bhatia

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We have earlier shown that mouse pancreatic acinar cells produce hydrogen sulfide (H2S) and play a role in the pathogenesis of acute pancreatitis. This study is to determine the effect of H2S on TLR4 mediated innate immune signaling in acute pancreatitis via substance P (SP). Male Swiss mice were treated with hourly intraperitoneal injection of caerulein (50μg/kg) for 10 hour. DL-propargylglycine (PAG) (100 mg/kg i.p.), an inhibitor of H2S formation was administered 1h after the induction of acute pancreatitis. Pancreatic acinar cells from male Swiss mice were incubated with or without caerulein (10–7 M for 60 min) and CP-96345 (NK1R inhibitor). To better understand the effect of H2S in inflammation, acinar cells were stimulated with caerulein after addition of H2S donor, NaHS. In addition, caerulein treated pancreatic acinar cells were pretreated with PAG (30 µM), for 1h. H2S inhibitor, PAG, eliminated TLR4, IRAK4, TRAF6 and NF-kB levels in an in vitro and in vivo model of caerulein-induced acute pancreatitis. PPTA gene deletion reduced TLR4, MyD88, IRAK4, TRAF6, adhesion molecules and NF-kB in caerulein treated pancreatic acinar cells whereas administration of NaHS resulted in further rise in TLR4 and NF-kB levels in caerulein treated pancreatic acinar cells. In addition, acini isolated from mice and treated with PPTA gene receptor NK1R antagonist CP96345 did not exhibit further increase in TLR4, IRAK4, TRAF6, adhesion molecules and NF-kB levels after NaHS pretreatment. The present findings show for the first time that in acute pancreatitis, H2S up-regulates TLR4 pathway and NF-kB via substance P.

Keywords: preprotachykinin-A gene, H2S, TLR4, acute pancreatitis

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Authors: Salma Baig, Bakrudeen Ali Ahmad, Ainnul Hamidah Syahadah Azizan, Hapipah Mohd Ali, Elham Rouhollahi, Mahmood Ameen Abdulla

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Free radical damage induced by reactive oxygen species (ROS) contributes to etiology of many chronic diseases, cancer being one of them. Recent studies have been successful in ROS targeted therapies via antioxidants using mouse models in cancer therapeutics. The present study was designed to scrutinize anticancer activity, antioxidant activity of 5 different extracts of Thymus serpyllum in MDA-MB-231, MCF-7, HepG2, HCT-116, PC3, and A549. Identification of the phytochemicals present in the most active extract of Thymus serpyllum was conducted using gas chromatography coupled with mass spectrophotometry and antioxidant activity was measured by using DPPH radical scavenging and FRAP assay. Anticancer impact of the extract in terms of IC50 was evaluated using MTT cell viability assay. Results revealed that the hexane extract showed the best anticancer activity in HepG2 (Liver Carcinoma Cell Line) with an IC50 value of 23 ± 0.14 µg/ml followed by 25 µg/ml in HCT-116 (Colon Cancer Cell Line), 30 µm/ml in MCF-7 (Breast Cancer Cell Line), 35 µg/ml in MDA-MB-231 (Breast Cancer Cell Line), 57 µg/ml in PC3 (Prostate Cancer Cell Line) and 60 µg/ml in A549 (Lung Carcinoma Cell Line). GC-MS profile of the hexane extract showed the presence of 31 compounds with carvacrol, thymol and thymoquione being the major compounds. Phenolics such as Vitamin E, terpinen-4-ol, borneol and phytol were also identified. Hence, here we present the first report on cytotoxicity of hexane extract of Thymus serpyllum extract in HepG2 cell line with a robust anticancer activity with an IC50 of 23 ± 0.14 µg/ml.

Keywords: Thymus serpyllum L., hexane extract, GC-MS profile, antioxidant activity, anticancer activity, HepG2 cell line

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Authors: Dina F. Mansour, Dalia O. Saleh, Rasha E. Mostafa

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Cyclophosphamide (CP), the most commonly used chemotherapeutic agent, was reported to cause many side effects including urotoxicity, cardiotoxicity, gonadotoxicity, and hepatotoxicity; this limits its clinical practice. In the present study, the protective effect of genistein (GEN), the major phytoestrogen in soy products that possesses various pharmacological activities, has been investigated against CP-induced acute liver damage in rats. Forty adult Sprague-Dawley rats were allocated into five groups. The first group received the vehicles and act as normal control. In the other groups, rats were injected with a single dose of CP (200 mg/kg, i.p). The last three groups were pretreated with subcutaneous GEN at doses of 0.5, 1 and 2 mg/kg/day, respectively, for 15 consecutive days prior CP injection. Forty-eight hours following CP injection, rats of all groups were investigated for the serum levels of alanine transaminase and aspartate transaminase, as well as the liver contents of reduced glutathione, malondialdehyde, nitrite, interleukin-1β, and myeloperoxidase. Histopathological examination of liver tissues was also conducted. CP resulted in acute liver damage in rats as evidenced by alteration of liver function biomarkers, oxidative stress, and inflammatory markers; that was confirmed by the histopathological outcomes. Pretreatment of rats with GEN significantly protected against CP-induced deterioration of liver function and showed marked anti-oxidant and anti-inflammatory properties that were demonstrated by the biochemical and histopathological findings. In conclusion, the present findings demonstrated the protective effects of GEN against CP-induced liver damage and suggested role of its antioxidant and anti-inflammatory activities.

Keywords: cyclophosphamide, genistein, inflammation, interleukin-1β, liver, myeloperoxidase, oxidative stress

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Authors: Ahmed M. Kabel, Maaly A. Abd Elmaaboud

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Scleroderma is one of the connective tissue disorders characterized by skin and systemic fibrosis. Its pathogenesis involves multiple interrelated processes of autoimmunity, vasculopathy, inflammation, and oxidative stress. This study was a trial to explore the possible ameliorative effects of sodium valproate on an experimental model of skin fibrosis induced by bleomycin. Forty male BALB/c mice were divided into four equal groups as follows: control group; bleomycin group; bleomycin + sodium valproate group, and sodium valproate group. Mice were assessed for their body weight every four days throughout the whole study. Skin tissues were used to evaluate the oxidative stress parameters, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 15, and mammalian target of rapamycin (mTOR). Skin fibrosis was evaluated by measuring dermal thickness and staining the skin tissues with Masson trichrome stain. Also, the skin tissues were immunostained with alpha smooth muscle actin (α-SMA). Administration of sodium valproate to bleomycin-treated mice resulted in the restoration of the body weight with a significant decrease in the dermal thickness, amelioration of oxidative stress, suppression of TGF-β1 and mTOR expression, and significant reduction of the percentage of α-SMA immunostaining and the proinflammatory cytokine levels compared to mice treated with bleomycin alone. In conclusion, sodium valproate has an antifibrotic effect on skin fibrosis which may represent a beneficial therapeutic modality for the management of scleroderma.

Keywords: scleroderma, bleomycin, sodium valproate, skin fibrosis

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Authors: Arslan Masood Pirzada, Muhammad Naeem, Hafiz Haider Ali, Muhammad Latif, Aown Sammar Raza, Asad Hussain Bukhari, Muhammad Saqib, Muhammad Ijaz

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Cyperus rotundus (Cyperaceae), a medicinal herb, is being traditionally used as a home remedy for the treatment of various clinical conditions like diarrhea, diabetic, pyretic, inflammation, malaria, and for treating stomach and bowel disorders. Its current status is one of the most widespread, troublesome, and economically damaging agronomic weeds, growing wildly in various tropical and sub-tropical regions of the world. Tuber and rhizomes of Cyperus rotundus possess a higher concentration of active ingredients in the form of essential oils, phenolic acids, ascorbic acids and flavonoids, responsible for its remedial properties. Exploitation of any medicinal plant application depends on the crucial and comprehensive information about the therapeutic potential of a plant. Researchers have evaluated and characterized the significance of Cyperus rotundus as an anti-androgenic, anti-bacterial, anti-cancerous, anti-convulsant, anti-diabetic, anti-diarrheal, anti-genotoxic, anti-inflammatory, anti-lipidemic, anti-malarial, anti-mutagenic, anti-obesity, anti-oxidant, anti-uropathogenic, hepato-, cardio-, neuroprotective, and nootropic agent. This paper comprises a broad review to summarize the current state of knowledge about chemical constituents, potential economic uses and therapeutic aspects of Cyperus rotundus that will aid in the development of bioethanol and modern herbal medicine through latest technologies that will promote the ability of this plant in the cure of many clinical disorders.

Keywords: purple nutsedge, chemical composition, economic uses, therapeutic values, future directions

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Authors: Xu Yifei, Le Yining, Yang Qingluan, Tu Yanjie

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Objective: This study aims to investigate the distribution features of Traditional Chinese Medicine (TCM) syndromes and syndrome elements in Epstein-Barr virus-associated diseases and then explores the relations between TCM syndromes or syndrome elements and laboratory indicators of Epstein-Barr virus-associated diseases. Methods: A cross-sectional study of 70 patients with EBV infection was described. We assessed the diagnostic information and laboratory indicators of these patients from Huashan Hospital Affiliated to Fudan University between November 2017 and July 2019. The disease diagnosis and syndrome differentiation were based on the diagnostic criteria of EBV-associated diseases and the theory of TCM respectively. Confidence correlation analysis, logistic regression analysis, cluster analysis, and the Sankey diagram were used to analyze the correlation between the data. Results: The differentiation of the 4 primary TCM syndromes in the collected patients was correlated with the indexes of immune function, liver function, inflammation, and anemia, especially the relationship between Qifen syndrome and high lactic acid dehydrogenase level. The common 11 TCM syndrome elements were associated with the increased CD3+ T cell rate, low hemoglobin level, high procalcitonin level, high lactic acid dehydrogenase level, and low albumin level. Conclusion: The changes in immune function indexes, procalcitonin, and liver function-related indexes in patients with EBV-associated diseases were consistent with the evolution law of TCM syndromes. This study provides a reference for judging the pathological stages of these kinds of diseases, predicting their prognosis, and guiding subsequent treatment strategies based on TCM syndrome type.

Keywords: EBV-associated diseases, traditional Chinese medicine syndrome, syndrome element, diagnostics

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Authors: Hsiao-Chuan Huang, King-Lung Kuo, Mei-Hsin Lo, Hsiao-Yun Chou, Yusen Lin

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The most robust and economical method for laboratory diagnosis of TB is to identify mycobacterial bacilli (AFB) under acid-fast staining despite its disadvantages of low sensitivity and labor-intensive. Though digital pathology becomes popular in medicine, an automated microscopic system for microbiology is still not available. A new AI-assisted automated microscopic system, consisting of a microscopic scanner and recognition program powered by big data and deep learning, may significantly increase the sensitivity of TB smear microscopy. Thus, the objective is to evaluate such an automatic system for the identification of AFB. A total of 5,930 smears was enrolled for this study. An intelligent microscope system (TB-Scan, Wellgen Medical, Taiwan) was used for microscopic image scanning and AFB detection. 272 AFB smears were used for transfer learning to increase the accuracy. Referee medical technicians were used as Gold Standard for result discrepancy. Results showed that, under a total of 1726 AFB smears, the automated system's accuracy, sensitivity and specificity were 95.6% (1,650/1,726), 87.7% (57/65), and 95.9% (1,593/1,661), respectively. Compared to culture, the sensitivity for human technicians was only 33.8% (38/142); however, the automated system can achieve 74.6% (106/142), which is significantly higher than human technicians, and this is the first of such an automated microscope system for TB smear testing in a controlled trial. This automated system could achieve higher TB smear sensitivity and laboratory efficiency and may complement molecular methods (eg. GeneXpert) to reduce the total cost for TB control. Furthermore, such an automated system is capable of remote access by the internet and can be deployed in the area with limited medical resources.

Keywords: TB smears, automated microscope, artificial intelligence, medical imaging

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Authors: Rashmi Ranade, Neelu Joshi

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Barleria prionitis L. is a well explored Indian medicinal plant valued for its stem and leaf which forms an important ingredient of many Ayurvedic formulations. It is used for the treatment of various disorders like toothache, bleeding gums, strengthening gums, whooping cough, inflammation, arthritis, enlargement of scrotum and sciatica etc. The plant is propagated vegetatively through stem cuttings. Frequent harvesting of this plant has led to the shortage of planting material, and it has acquired the status of vulnerable plant species. Plant tissue culture technology offers a very good alternative for propagation and conservation of such plant species. The present investigation was undertaken to develop in vitro regeneration protocol for B. prionitis L. via callus organogenesis pathway. Stem and leaf explants were used for this purpose. Different media and plant growth regulators were optimized to develop the protocol. The problem of phenol secretion and browning and in vitro cultures at the establishment phase was successfully curbed with the usage of antibrowning agents such as ascorbic acid and activated charcoal. Optimum shoot multiplication was achieved by the use of liquid media and incorporation of silver nitrate and TIBA (triiodobenzoic acid) into the media. High percent rooting (76%) was observed on WPM media supplemented with IBA (2.0 mg/l), IAA (0.5 mg/l), GA3(0.5) and activated charcoal(500 mg/l). The rooted plantlets were subjected to in vitro hardening on sterile potting mix (soil:farmyard manure:compost; 1:2:1) and acclimatized under greenhouse conditions. Around 85% survival of plantlets was recorded upon acclimatization. This lab scale protocol would be tested for in vitro scaling up production of B. prionitis L.

Keywords: explant browning, liquid culture, micropropagation, shoot multiplication, phenolic secretion

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Authors: Bahar Tunctan, Sefika Pinar Kucukkavruk, Meryem Temiz-Resitoglu, Demet Sinem Guden, Ayse Nihal Sari, Seyhan Sahan-Firat, Mahesh P. Paudyal, John R. Falck, Kafait U. Malik

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We hypothesized that 20-hydroxyeicosatetraenoic acid (20-HETE) mimetics such as N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE) may be beneficial for preventing mortality due to inflammation induced by lipopolysaccharide (LPS). This study aims to assess the effect of 5,14-HEDGE on the LPS-induced changes in nucleotide binding domain and leucine-rich repeat protein 3 (NLRP3)/apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC)/pro-caspase-1 inflammasome. Rats were injected with saline (4 ml/kg) or LPS (10 mg/kg) at time 0. Blood pressure and heart rate were measured using a tail-cuff device. 5,14-HEDGE (30 mg/kg) was administered to rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and kidney, heart, thoracic aorta, and superior mesenteric artery were isolated for measurement of caspase-1/11 p20, NLRP3, ASC, and β-actin proteins as well as interleukin-1β (IL-1β) levels. Blood pressure decreased by 33 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. In the LPS-treated rats, tissue protein expression of caspase-1/11 p20, NLRP3, and ASC in addition to IL-1β levels were increased. 5,14-HEDGE prevented the LPS-induced changes. Our findings suggest that inhibition of renal, cardiac, and vascular formation/activity of NLRP3/ASC/pro-caspase-1 inflammasome involved in the protective effect of 5,14-HEDGE on LPS-induced septic shock in rats. This work was financially supported by the Mersin University (2015-AP3-1343) and USPHS NIH (PO1 HL034300).

Keywords: 5, 14-HEDGE, lipopolysaccharide, NLRP3, inflammasome, septic shock

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Authors: Faraz Zarghami, Elham Anari, Nosratollah Zarghami, Yones Pilehvar-Soltanahmadi, Abolfazl Akbarzadeh, Sepideh Jalilzadeh-Tabrizi

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The development of nanotherapy has presented a new method of drug delivery targeted directly to the neoplasmic tissues, to maximize the action with fewer dose requirements. In the past two decades, poly(lactic-co-glycolic acid) (PLGA) has frequently been investigated by many researchers and is a popular polymeric candidate, due to its biocompatibility and biodegradability, exhibition of a wide range of erosion times, tunable mechanical properties, and most notably, because it is a FDA-approved polymer. Chrysin is a natural flavonoid which has been reported to have some significant biological effects on the processes of chemical defense, nitrogen fixation, inflammation, and oxidation. However, the low solubility in water decreases its bioavailability and consequently disrupts the biomedical benefits. Being loaded with PLGA-PEG increases chrysin solubility and drug tolerance, and decreases the discordant effects of the drug. The well-structured chrysin efficiently accumulates in the breast cancer cell line (T47D). In the present study, the structure and chrysin loading were delineated using proton nuclear magnetic resonance (HNMR), Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM), and the in vitro cytotoxicity of pure and nanochrysin was studied by the MTT assay. Next, the RNA was exploited and the cytotoxic effects of chrysin were studied by real-time PCR. In conclusion, the nanochrysin therapy developed is a novel method that could increase cytotoxicity to cancer cells without damaging the normal cells, and would be promising in breast cancer therapy.

Keywords: MTT assay, chrysin, flavonoids, nanotherapy

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Authors: Saut Samuel Simamora

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PURPOSE: Nucleus drop is one of the most feared and severe complications of modern cataract surgery. The lens material may drop through iatrogenic breaks of the posterior capsule. The incidence of the nucleus as the complication of phacoemulsification increases concomitant to the increased frequency of phacoemulsification. Pars plana vitrectomy (PPV) followed by endofragmentation and secondary intraocular lens (IOL) implantation is the choice of management procedure. This case report aims to present the outcome of PPV for the treatment dropped nucleus after cataract surgery METHODS: A 65 year old female patient came to Vitreoretina department with chief complaints blurry vision in her left eye after phacoemulsification one month before. Ophthalmological examination revealed visual acuity of the right eye (VA RE) was 6/15, and the left eye (VA LE) was hand movement. The intraocular pressure (IOP) on the right eye was 18 mmHg, and on the left eye was 59 mmHg. On her left eye, there were aphakic, dropped lens nucleus and secondary glaucoma.RESULTS: The patient got antiglaucoma agent until her IOP was decreased. She underwent pars plana vitrectomy to remove dropped nucleus and iris fixated IOL. One week post operative evaluation revealed VA LE was 6/7.5 and iris fixated IOL in proper position. CONCLUSIONS: Nucleus drop generally occurs in phacoemulsification cataract surgery techniques. Retained lens nucleus or fragments in the vitreous may cause severe intraocular inflammation leading to secondary glaucoma. The proper and good management for retained lens fragments in nucleus drop give excellent outcome to patient.

Keywords: secondary glaucoma, complication of phacoemulsification, nucleus drop, pars plana vitrectomy

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Authors: Alireza Jafarzadeh, Samad Mosaferi, Mansour Khakpour

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Mastitis is an inflammation of the parenchyma of mammary gland regardless of the causes. Mastitis is characterized by a range of physical and chemical changes in the glandular tissue. The most important change in milk includes discoloration, the presence of clots and large number of leucocytes. There is swelling, heat, pain and edema in mammary gland in many clinical cases. Positive coagulase S. aureus is a major pathogen of the bovine mammary gland and a common cause of contagious mastitis in cattle. The aim of this study was to evaluate the outbreaks of Staphylococcus aureus mastitis. This study is conducted in ten dairy herds about one thousand cows. After doing CMT and identifying infected cows, the milk samples obtained from infected teats and transported to microbiological laboratories. After microbial culture of milk samples and isolating S. aureus, antimicrobial, sensitivity test was performed with disk diffusion method by ciprofloxacin, co-amoxiclav, erythromycin, penicillin, oxytetracyclin, sulfonamides, lincomycin and cefquinome. The study defined that the outbreak of subclinical positive coagulase Staphylococcus mastitis in dairy herd was 13.11% (5.6% S. aureus and 7.51% S. intermedicus). The antimicrobial sensitivity test shown that 87.23% of Staphylococcus aureus isolated from bovine mastitis in dairy herd was susceptible to ciprofloxacin, 93.9% to cefquinome, 4.67% to co-amoxiclav, 12.16% to erythromycin 86.11% to sulfonamides (co-trimoxazole), 3.35% lincomycin, 12.7% to oxytetracyclin and 5.98% to penicillin. Results of present defined that ciprofloxacin has a great effect on Staphylococcus aureus isolated from subclinical bovine mastitis dairy herd. It seems that cefquinome sulfonamides has a great effect on isolated Staphylococcus aureus in vivo.

Keywords: ciprofloxacin, mastitis, Staphylococcus aureus, dairy herd

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Authors: S. Potgieter-Vermaak, N. Bain, A. Brown, K. Shaw

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It is well-known from public news media that air pollution is a health hazard and is responsible for early deaths. The quantification of the relationship between air quality and health is a probing question not easily answered. It is known that airborne particulate matter (APM) <2.5µm deposits in the tracheal and alveoli zones and our research probes the possibility of quantifying pulmonary injury by linking reactive oxygen species (ROS) in these particles to DNA damage. Currently, APM mass concentration is linked to early deaths and limited studies probe the influence of other properties on human health. To predict the full extent and type of impact, particles need to be characterised for chemical composition and structure. APMs are routinely analysed for their bulk composition, but of late analysis on a micro level probing single particle character, using micro-analytical techniques, are considered. The latter, single particle analysis (SPA), permits one to obtain detailed information on chemical character from nano- to micron-sized particles. This paper aims to provide a snapshot of studies using data obtained from chemical characterisation and its link with in-vitro studies to inform on personal health risks. For this purpose, two studies will be compared, namely, the bioaccessibility of the inhalable fraction of urban road dust versus total suspended solids (TSP) collected in the same urban environment. The significant influence of metals such as Cu and Fe in TSP on DNA damage is illustrated. The speciation of Hg (determined by SPA) in different urban environments proved to dictate its bioaccessibility in artificial lung fluids rather than its concentration.

Keywords: air pollution, human health, in-vitro studies, particulate matter

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Authors: Eric Beyegue, Boris Azantza, Judith Laure Ngondi, Julius E. Oben

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Background: Dietary supplement may potentially help to fight obesity and other metabolic disorders such as adipogenesis, insulin resistance, and inflammation. The present study aimed to test whether supplementation with African walnuts (Aw) could have an effect on adipogenesis and others dysfunctions associated with obesity in rats. Methods: Wistar rats were fed with standard diet (SD) or high-fat high-sucrose diet (HFS) and HFS with supplemented (HFS-Aw) for eight weeks. Results: HFS diet-induced body weight gain and increased fat mass compared to SD. In addition HFS-fed rats developed fasting hyperglycaemia and insulinaemia as well as insulin resistance. Aw supplementation in HFS rats had a protective effect against adipose tissues weigh gain but slightly against body weight gain and major study related disorders. This could be mainly due to decreased food intake dependently of effect in food intake in central nervous system, which decreased in HFS rats supplemented with African walnut compared to the HFS-diet group. Interestingly, African walnut supplementation induced a slight decrease of fasting glycaemia, insulinaemia and Nitric Oxide which could partially explain its minor protective effect against diet-induced insulin resistance. Additionally a decrease in hepatic TG and transaminases levels suggesting a protective effect against liver injury. Conclusion: Taken together these data suggested that supplementation of African walnut could be used to prevent adipose weight gain and related disorders on the other hand, minimally reduced insulin resistance.

Keywords: African walnut, dietary fiber, insulin resistance, oxidative stress

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Authors: Stefan Gruden, Charlott Brunmark, Bo Holmqvist, Erwin D. Brenndorfer, Martin Johansson, Jian Liu, Ying Zhao, Niklas Axen, Moustapha Hassan

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Aim: The study was designed to evaluate the ability of the calcium sulfate-based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity. Methods: NanoZolid-formulated EGF protein labelled with a near-infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 hours post-administration, utilizing whole-body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling. Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression. Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g., receptor binding capability. This may have good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.

Keywords: bioresorbable, calcium sulfate, controlled release, NanoZolid

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Authors: Gulam Anwer Khan, A. Gautam

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Background: The arch of aorta is a large artery that arches over the root of the left lung and connects the ascending aorta and descending aorta. It is situated in the superior mediastinum behind the manubrium sterni. It gives off three major branches i.e. brachiocephalic trunk, left common carotid artery and left subclavian artery arising from the superior surface of arch of aorta from right to left. Material and Methods: This was a descriptive study. It was carried out in 44 cadavers, obtained during dissections for undergraduates of Department of Anatomy, Chitwan Medical College, Bharatpur, Chitwan, between March 2015 to October 2016. Cadavers of both sexes were included in the present study. The arch of aorta was dissected and exposed according to the methods described by Romanes in Cunningham’s manual of practical anatomy. Results: Out of 44 dissected cadavers, 35 (79.54%) were male and 9 (20.46%) were female cadavers. The normal branching pattern of the arch of aorta was encountered in 28 (63.64%) cadavers and the remaining 16 (36.36%) cadavers showed variations in the branching pattern of arch of aorta. Two different types of variations on the branching pattern of arch of aorta were noted in the present study, in which 12 (27.27%) cadavers had common trunk of the Arch of Aorta. In 3 (5.00%) male cadavers, we found the origin of the Thyroid ima artery. This variation was noted in 1(1.66%) female cadaver. Conclusion: The present study carried out on adult human cadavers’ revealed wide variations in the branching pattern of the arch of ao rta. These variations are of clinical significance and also very useful for the anatomists, radiologists, anesthesiologists, surgeons for practice during angiography, instrumentation, supra-aortic thoracic, head and neck surgery.

Keywords: arch of aorta, brachiocephalic trunk, left common carotid artery, left subclavian artery, Thyroidea ima artery

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Authors: Somaiya Mateen, Shagufta Moin, Mohammad Owais, Abdul Khan, Atif Zafar

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In rheumatoid arthritis (RA), impaired oxidative metabolism and imbalance between pro-and anti-inflammatory cytokines are responsible for causing inflammation and the degradation of cartilage and bone. The present study was done to evaluate the level and hence the role of reactive oxygen species (ROS) and inflammatory cytokines in the pathogenesis of RA. The present study was performed in the blood of 80 RA patients and 55 age and sex-matched healthy controls. The level of ROS (in 5% hematocrit) and the plasma level of pro-inflammatory cytokines [TNF-α, interleukin-6 (IL-6), IL-22] and anti-inflammatory cytokines (IL-4 and IL-5) were monitored in healthy subjects and RA patients. For evaluating the role of rheumatoid factor (RF) in the pathogenesis of RA, patients were sub-divided on the basis of presence or absence of RF. Reactive species and inflammatory cytokines were correlated with disease activity measure-Disease Activity Score for 28 joints (DAS28). The level of ROS, TNF-α, IL-6 and IL-22 were found to be significantly higher in RA patients as compared to the healthy controls, with the increase being more significant in patients positive for rheumatoid factor and those having high disease severity. On the other hand, a significant decrease in the level of IL-4 and IL-10 were observed in RA patients compared with healthy controls, with the decrease being more prominent in severe cases of RA. Higher ROS (indicative of impaired anti-oxidant defence system) and pro-inflammatory cytokines level in RA patients may lead to the damage of biomolecules which in turn contributes to tissue damage and hence to the development of more severe RA. The imbalance between pro-and anti-inflammatory cytokines may lead to the development of multi-system immune complications. ROS and inflammatory cytokines may also serve as a potential biomarker for assessing the disease severity.

Keywords: rheumatoid arthritis, reactive oxygen species, pro-inflammatory cytokines, anti-inflammatory cytokines

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Authors: Barbara Torres Rives

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Uveitis. Non-infectious anterior uveitis is a polygenic inflammatory eye disease, and it is suggested that mediated processes by the immune system (autoimmune or not) are the main mechanisms proposed in the pathogenesis of this type of uveitis. A relationship between infectious processes, digestive disorders, and a dysbiosis of the microbiome was recently described. In addition, alterations in the immune response associated with the initiation and progression of the disease have been described. Objective: The aim of this study was to identify factors related to the immune system associated with complicated non-infectious anterior uveitis. Methods: A cross-sectional observational analytical study was carried out. The universe consisted of all patients attending the ocular inflammation service of the Cuban Institute of Ophthalmology Ramón Pando Ferrer. The sample consisted of 213 patients diagnosed with non-infectious anterior uveitis. Results: Of the 213 patients with non-infectious anterior uveitis, the development of ophthalmologic complications predominated 56.3% (p=0.0094). In patients with complications was more frequent the presence of human leukocyte antigen-B27 allele (49.2%) (p<0.0001), decreased immunoglobulin G (24.2%, p=0.0124), increased immunoglobulin A (14.2%, p=0.0024), history of recurrent sepsis (59.2%, p=0.0018), recurrent respiratory infections (44.2%, p=0.0003), digestive alterations (40%, p=0.0013) and spondyloarthropathies (30%, p=0.0314). By logistic regression, it was observed that, for each completed year, the elevated risk for developing complicated non-infectious anterior uveitis in human leukocyte antigen-B27 allele positive patients (OR: 4.22, p=0.000), Conclusions: The control of recurrent sepsis at mucosal level and immunomodulation could prevent complications in non-infectious anterior uveitis. Therefore, the microbiome becomes the target of treatment and prevention of complications in non-infectious anterior uveitis.

Keywords: non-infectious anterior uveitis, immune system disorders, recurrent mucosal infections, microbiome

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Authors: Harshadkumar Rajgor, Jeff Butterworth

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Background: Barretts oesophagus increases the risk of developing oesophageal adenocarcinoma. Over the last 40 years, there has been a 6 fold increase in the incidence of oesophageal adenocarcinoma in the western world and the incidence rates are increasing at a greater rate than cancers of the colon, breast and lung. Endoscopic mucosal resection (EMR) is a relatively new technique being used by 2 centres in the greater midlands cancer network. EMR can be used for curative or staging purposes, for high-grade dysplasia’s and T1 tumours of the oesophagus. EMR is also suitable for those who are deemed high risk for oesophagectomy. EMR has a recurrence rate of 21% according to the Wiesbaden data. Method: A retrospective study of prospectively collected data was carried out involving 24 patients who had EMR for curative or staging purposes. Complications of residual or recurrent disease following EMR that required further treatment were investigated. Results: In 54% of cases residual or recurrent disease was suspected. 96% of patients were given clear and concise information regarding their diagnosis of high-grade dysplasia or T1 tumours. All 24 patients consulted the same specialist healthcare team. Conclusion: EMR is a safe and effective treatment for patients who have high-grade dysplasia and T1NO tumours. In 54% of cases residual or recurrent disease was suspected. Initially, only single resections were undertaken. Multiple resections are now being carried out to reduce the risk of recurrence. Complications from EMR remain low in this series and consisted of a single episode of post procedural bleeding.

Keywords: endoscopic mucosal resection, oesophageal dysplasia, T1 tumours, cancer network

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Authors: Pranee Suecharoen, Jaturat Kanpittaya

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Background: The incidence of adverse reactions to iodinated contrast media has risen. The dearth of reports on reactions to the administration of iso- and low-osmolar contrast media should be addressed. We, therefore, studied the profile of adverse reactions to iodinated contrast media; viz., (a) the body systems affected (b) causality, (c) severity, and (d) preventability. Objective: To study adverse reactions (causes and severity) to iodinated contrast media at Srinagarind Hospital. Method: Between March and July, 2015, 1,101 patients from the Department of Radiology were observed and interviewed for the occurrence of adverse reactions. The patients were classified per Naranjo’s algorithm and through use of an adverse reactions questionnaire. Results: A total of 105 cases (9.5%) reported adverse reactions (57% male; 43% female); among whom 2% were iso-osmolar vs. 98% low-osmolar. Diagnoses included hepatoma and cholangiocarcinoma (24.8%), colorectal cancer (9.5%), breast cancer (5.7%), cervical cancer (3.8%), lung cancer (2.9%), bone cancer (1.9%), and others (51.5%). Underlying diseases included hypertension and diabetes mellitus type 2. Mild, moderate, and severe adverse reactions accounted for 92, 5 and 3%, respectively. The respective groups of escalating symptoms included (a) mild urticaria, itching, rash, nausea, vomiting, dizziness, and headache; (b) moderate hypertension, hypotension, dyspnea, tachycardia and bronchospasm; and (c) severe laryngeal edema, profound hypotension, and convulsions. All reactions could be anticipated per Naranjo’s algorithm. Conclusion: Mild to moderate adverse reactions to low-osmolar contrast media were most common and these occurred immediately after administration. For patient safety and better outcomes, improving the identification of patients likely to have an adverse reaction is essential.

Keywords: adverse reactions, contrast media, computed tomography, iodinated contrast agents

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Authors: Rania Hanafi Said, Rasha Mohamed Taha

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Background: By using nanoparticles as drug delivery, it may be possible to avoid the drawbacks of systemic antibiotic dosing, including bacterial antibiotic resistance. The goal of this study was to see how well tetracycline loaded on nanochitosan worked to treat gingival inflammation in albino rats caused by Porphyromonas gingivalis. The study analyzed immunohistochemically the localization of the pro-inflammatory cytokine Interleukin-1beta (IL-1β). Material and methods: In this study, fifty mature male albino rats weighing 150 to 180 grams each were used. They were randomly divided into five groups. We checked for weight changes in rats. Ten male albino rats were included in Group I, which served as a negative control group. Ten rats were included in Group II, where they were exposed once to Porphyromonas. Group III contained ten rats, which were treated the same as Group II plus daily injections of diluted tetracycline powder at the infection sites. Ten rats in Group IV received the same procedure as those in Group II before receiving daily injections of nanochitosan at the injection sites. Finally, Group V, which had ten rats. Following the same protocol as Group II, they received localized injections of tetracycline loaded on nanochitosan once daily. Rats' gingivae were extracted and prepared after they were anesthetized. The biopsies were examined histologically and immunohistochemically by light microscopy. Results: Groups I and V had a nearly normal histological appearance of gingival tissue. In Groups II, III, and IV, degeneration was seen because the epithelial cells were bigger, collagen fibers were pulling away from the lamina propria connective tissue, and the basement membranes had come to an end. There was no discernible difference between groups V and I when they were examined immunohistochemically. Conclusion: The use of nano chitosan as a tetracycline carrier is a novel technique to overcome the drug's rising level of resistance.

Keywords: Immunohistochemistry, Nanochitosan, porphyromonas gingivitis, Tetracycline

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Authors: Sachin K. Samuchiwal, Barbara Balestrieri, Amanda Paskavitz, Hannah Raff, Joshua A. Boyce

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IL-33, a recently discovered member of the IL-1 cytokine family, binds to the TLR/IL1R super family receptor ST2 and induces type 2 immune responses. IL-33 is constitutively expressed in structural cells at barrier sites such as skin, lung, and intestine, and also inducibly expressed by hematopoietic cells including macrophages. Stimulation of macrophages by Lipopolysaccharide (LPS) can induce de novo IL-33 expression, and also causes the production of prostaglandin-E2 (PGE2) via cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1 (mPGES-1). Because PGE2 can regulate macrophage functions through both autocrine and paracrine mechanisms, the potential interplay of endogenous PGE2 on IL-33 production was explored. Bone-marrow derived murine macrophages (bmMF) that lack either mPGES-1 or EP2 receptor expression were stimulated with LPS in the absence or presence of exogenous PGE2 along with pharmacological agonists and antagonists. The study results demonstrate that endogenous PGE2 markedly enhances LPS-induced IL-33 production by bmMFs via EP2 receptors. Moreover, exogenous PGE2 can amplify LPS-induced IL-33 expression dominantly by EP2 and partly by EP4 receptors by a pathway involving cAMP and exchange protein activated by cAMP (EPAC), but not protein kinase A (PKA). Though both IL-33 production and PGE2 generation in response to LPS require activation of both p38 MAPK and NF-κB, PGE2 did not influence this activation. In conclusion, it is demonstrated that endogenous PGE2 signaling through EP2 and EP4 receptors is a prerequisite for LPS-induced IL-33 production in bmMFs and the underlying cAMP mediated pathway involves EPAC. Since IL-33 is a critical pro-inflammatory cytokine in various pathological disorders, this PGE2-EP2/EP4-cAMP mediated pathway can be exploited to intervene in IL-33 driven pathologies.

Keywords: bone marrow macrophages, EPAC, IL-33, PGE2

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Authors: A. M. Bumbea, A. Musetescu, P. Ciurea, A. Bighea

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Objectives: The authors present a Parsonage Turner syndrome, a rare disease characterized by onset in apparently healthy person with shoulder and/or arm pain, sensory deficit, motor deficit. The causes are not established, could be determinate by vaccination, postoperative, immunologic disease, post traumatic etc. Methods: The authors present a woman case, 32 years old, (in 2006), no medical history, with arm pain and no other symptom. The onset was sudden with pain at very high level quantified as 10 to a 0 to 10 scale, with no response to classical analgesic and corticoids. The only drugs which can reduce the intensity of pain were oxycodone hydrochloride, 60 mg daily and pregabalinum150 mg daily. After two weeks the intensity of pain was reduced to 5. The patient started a rehabilitation program. After 6 weeks the patient associated sensory and motor deficit. We performed electromyography for upper limb that showed incomplete denervation with reduced neural transmission speed. The patient receives neurotrophic drugs and painkillers for a long period and physical and kinetic therapy. After 6 months the pain was reduced to level 2 and the patient maintained only 150 mg pregabalinum for another 6 months. Then, the evaluation showed no pain but general amiotrophy in upper limb. Results: At the evaluation in 2009, the patient developed a rheumatoid syndrome with tender and swelling joints, but no positive inflammation test, no antibodies or rheumatoid factor. After two years, in 2011 the patient develops an increase of antinuclear antibodies. This context certifies the diagnosis of lupus and the patient receives the specific therapy. Conclusions: This case is not a typical case of onset of lupus with PTS, but the onset of PTS could include the onset of an immune disease.

Keywords: lupus, arm pain, patient, swelling

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Authors: Dong-Gyu Leem, Ji-Sun Shin, Sang Yoon Choi, Kyung-Tae Lee

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In this study, we focused on the anti-proliferative effects of panaxydol, a C17 polyacetylenic compound derived from Panax ginseng roots, against various human cancer cells. We treated with panaxydol to various cancer cells and panaxydol treatment was found to significantly inhibit the proliferation of human lung cancer cells (A549) and human pancreatic cancer cells (AsPC-1 and MIA PaCa-2), of which AsPC-1 cells were most sensitive to its treatment. DNA flow cytometric analysis indicated that panaxydol blocked cell cycle progression at the G1 phase in A549 cells, which accompanied by a parallel reduction of protein expression of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D1 and cyclin E. CDK inhibitors (CDKIs), such as p21CIP1/WAF1 and p27KIP1, were gradually upregulated after panaxydol treatment at the protein levels. Furthermore, panaxydol induced the activation of p53 in A549 cells. In addition, panaxydol also induced apoptosis of AsPC-1 and MIA PaCa-2 cells, as shown by accumulation of subG1 and apoptotic cell populations. Panaxydol triggered the activation of caspase-3, -8, -9 and the cleavage of poly (ADP-ribose) polymerase (PARP). Reduction of mitochondrial transmembrane potential by panaxydol was determined by staining with dihexyloxacarbocyanine iodide. Furthermore, panaxydol suppressed the levels of anti-apoptotic proteins, XIAP and Bcl-2, and increased the levels of proapoptotic proteins, Bax and Bad. In addition, panaxydol inhibited the activation of Akt and extracellular signal-regulated kinase (ERK) and activated the p38 mitogen-activated protein kinase kinase (MAPK). Our results suggest that panaxydol is an anti-tumor compound that causes p53-mediated cell cycle arrest and apoptosis via mitochondrial apoptotic pathway in various cancer cells.

Keywords: apoptosis, cancer, G1 arrest, panaxydol

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Authors: Helen Huang, Francisco Javier Quesada Ocet, Blanca Quesada Oce, Javier Jimenez Bello, Victor Palanca Gil, Alba Cervero Rubio, Ana Paya Chaume, Alejandro Herreros-Pomares, Fernando Vidal-Vanaclocha, Rafael Paya Serrano, Aurelio Quesada Dorador, Monica Soliman

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Background: Cancer favors both the pro-inflammatory state and autonomic dysfunction, two important mechanisms in the genesis of AF. Atrial remodeling might be caused as a result of paraneoplastic conditions or the result of direct expression of neoplasia. Here, we hypothesize that cancer, through inflammatory mediators, may favor the appearance of AF and patients with the first episode of AF could have a higher risk of developing cancer. Method: Data was collected from patients who attended the emergency department of our hospital for the first episode of AF, diagnosed electrocardiographically, between 2010-2015 (n = 712). The minimum follow-up was 2 years, recording the appearance of cancer, total mortality, recurrences of AF and other events. Patients who developed cancer and those who did not during the 2 years after the onset of AF were compared, as well as with the incidence of cancer in Spain in 2012. Results: After 2 years, 35 patients (4.91%) were diagnosed with cancer, with an annual incidence of 2.45%. Hematological neoplasms were the most frequent (34.28%). The cancer group was older (76.68 +/-12.75 years vs 74.16 +/-12.71; p <0.05) and had fewer typical symptoms (palpitations) (33.38% vs 14.28% , p <0.05). The incidence of cancer in Spain during 2012 was 0.46%, much lower than our sample. When comparing the incidence by age, these differences were maintained both in those over 65 years of age and in those under 65 years of age (2.17% vs. 0.28%; 0.28% vs. 0.18% respectively). Discussion: Therefore, a high incidence of cancer in patients with the first episode of AF was observed (the annual incidence of 2.45% after the onset of AF is 6.1 times that of the general population). After the evaluation of patients with AF in their first detected episode, surveillance of the appearance of cancer should be considered in clinical practice.

Keywords: cancer, cardiovascular outcomes, atrial fibrillation, inflammation

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