Search results for: renal cancer

Authors: Ajay Kumar, Satwinderjeet Kaur

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Onosma bracteata Wall. (Boraginaceae), is known to be a medicinal plant, useful in the treatment of body swellings, abdominal pain and urinary calculi, etc. The present study focused on the radical scavenging and cancer growth inhibitory properties of isolates from O. bracteata. Obea fraction demonstrated noticeable free radical scavenging ability along with antiproliferative activity in human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung cancer A549 cell lines using MTT assay with GI50 values of 88.56, 101.61 and 112.7 μg/ml, respectively. The scanning electron and confocal microscopy studies showed morphological alterations including nuclear condensation and formation of apoptotic bodies in osteosarcoma MG-63 cells. Obea fraction in osteosarcoma MG-63 cells augmented the reactive oxygen species (ROS) level and decreased the mitochondrial membrane potential. Flow cytometry analysis revealed the Obea treated cells to be arrested in the G0/G1 phase in a dose dependent manner supported by the observed increase in the early apoptotic cell population. Western blotting analysis showed that the expression of p-NF-kB, COX-2, p-Akt, and Bcl-xL decreased whereas, the expression of GSK-3β, p53, caspase-3 and caspase-9 proteins increased. The downregulation of Bcl-2, Cyclin E, CDK2 and mortalin gene expression and upregulation of p53 genes was unfolded in RT-qPCR studies. The presence of catechin, kaempferol, Onosmin A and epicatechin, as revealed in high-performance liquid chromatography (HPLC) studies, contributes towards the chemopreventive potential of O. bracteata which can be tapped for chemotherapeutic use.

Keywords: apoptosis, confocal microscopy, HPLC, mitochondria membrane potential, reactive oxygen species

Procedia PDF Downloads 136

Authors: Sofia G. Meirinho, Luis G. Dias, António M. Peres, Lígia R. Rodrigues

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The emerging development of electrochemical aptasen sors has enabled the easy and fast detection of protein biomarkers in standard and real samples. Biomarkers are produced by body organs or tumours and provide a measure of antigens on cell surfaces. When detected in high amounts in blood, they can be suggestive of tumour activity. These biomarkers are more often used to evaluate treatment effects or to assess the potential for metastatic disease in patients with established disease. Osteopontin (OPN) is a protein found in all body fluids and constitutes a possible biomarker because its overexpression has been related with breast cancer evolution and metastasis. Currently, biomarkers are commonly used for the development of diagnostic methods, allowing the detection of the disease in its initial stages. A previously described RNA aptamer was used in the current work to develop a simple and sensitive electrochemical aptasensor with high affinity for human OPN. The RNA aptamer was biotinylated and immobilized on a gold electrode by avidin-biotin interaction. The electrochemical signal generated from the aptamer–target molecule interaction was monitored electrochemically using cyclic voltammetry in the presence of [Fe (CN) 6]−3/− as a redox probe. The signal observed showed a current decrease due to the binding of OPN. The preliminary results showed that this aptasensor enables the detection of OPN in standard solutions, showing good selectivity towards the target in the presence of others interfering proteins such as bovine OPN and bovine serum albumin. The results gathered in the current work suggest that the proposed electrochemical aptasensor is a simple and sensitive detection tool for human OPN and so, may have future applications in cancer disease monitoring.

Keywords: osteopontin, aptamer, aptasensor, screen-printed electrode, cyclic voltammetry

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Authors: Lokesh Bhatt, Jayesh Rathod

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Hypertension is one of the most prevalent cardiovascular disorder. It is responsible for several other cardiovascular disorders. Although many drugs are available for the treatment of hypertension, still a large population has uncontrolled blood pressure. Thus there is an unmet need for new therapeutic approaches for the same. Fruit juice of Citrus paradise contains several flavonoids with vasodilatory activity. We hypothesized that alcoholic extract of Citrus paradise, which contains flavonoids, might attenuate hypertension. The objective of the present study was to evaluate the antihypertensive activity of alcoholic extract of Citrus paradise fruit juice in rats. Hypertension was induced using one clip one kidney model in rats. The renal artery was occluded for 4 h after removal of one kidney. Once stabilized, the ganglionic blockade was performed followed by removal of the arterial clip from the kidney. Removal of clip resulted in an increase in blood pressure which is due to release of renin from the kidney. Alcoholic extract of Citrus paradise fruit juice was then administered at 50 mg/kg and 100 mg/kg dose by intravenous injection. Blood pressure was monitored continuously. Alcoholic extract of Citrus paradise fruit juice reduced hypertension in dose-dependent manner. Antihypertensive activity was found to be associated with vasodilation. The results of the present study showed antihypertensive potential of alcoholic extract of Citrus paradise fruit juice.

Keywords: citrus paradise, alcoholic extract, one clip one kidney model, vasodilation

Procedia PDF Downloads 289

Authors: André Furtado, Rafael Mineiro, Isabel Gonçalves, Cecília Santos, Telma Quintela

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The development of therapies for central nervous system (CNS) disorders is one of the biggest challenges of current pharmacology, given the unique features of brain barriers, which limit drug delivery. Efflux transporters (ABC transporters) expressed at the blood-cerebrospinal fluid barrier (BCSFB), are the main obstacles for the delivery of therapeutic compounds into the CNS, compromising the effective treatment of brain cancer, brain metastasis from peripheral cancers, or even neurodegenerative disorders. It is thus extremely important to understand the regulation of these transporters for reducing their expression while treating a brain disorder or choosing the most appropriate conditions for drug administration. Based on the fact that the BCSFB have fine-tuned biological rhythms, studying the circadian variation of drug transport processes is critical for choosing the most appropriate time of the day for drug administration. In our study, using an in vitro model of the BCSFB, we characterized the circadian transport profile of methotrexate (MTX) and donepezil (DNPZ), two drugs involved in the treatment of cancer and Alzheimer’s Disease symptoms, respectively. We found that MTX is transported across the basal and apical membranes of the BCSFB in a circadian way. The circadian pattern of an ABC transporter, Abcc4, might be partially responsible for MTX circadian transport. Furthermore, regarding the DNPZ transport study, we observed that the regulation of Abcg2 expression by the circadian rhythm will impact the circadian-dependent transport of DNPZ across the BCSFB. Overall, our results will contribute to the current knowledge on brain pharmacoresistance at the BCSFB by disclosing how circadian rhythms control drug delivery to the brain, setting the grounds for a potential application of chronotherapy to brain diseases to enhance the efficacy of medications and minimize their side effects.

Keywords: blood-cerebrospinal fluid barrier, ABC transporters, drug transport, chronotherapy

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Authors: G. Wagner, R. Herrmann

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Cytotoxic platinum compounds play a major role in the chemotherapy of a large number of human cancers. However, due to the severe side effects for the patient and other problems associated with their use, there is a need for the development of more efficient drugs and new methods for their selective delivery to the tumours. One way to achieve the latter could be in the use of nanoparticular substrates that can adsorb or chemically bind the drug. In the cell, the drug is supposed to be slowly released, either by physical desorption or by dissolution of the particle framework. Ideally, the cytotoxic properties of the platinum drug unfold only then, in the cancer cell and over a longer period of time due to the gradual release. In this paper, we report on our first steps in this direction. The binding properties of a series of cytotoxic Pt(II) oxadiazoline compounds to mesoporous silica particles has been studied by NMR and UV/vis spectroscopy. High loadings were achieved when the Pt(II) compound was relatively polar, and has been dissolved in a relatively nonpolar solvent before the silica was added. Typically, 6-10 hours were required for complete equilibration, suggesting the adsorption did not only occur to the outer surface but also to the interior of the pores. The untreated and Pt(II) loaded particles were characterised by C, H, N combustion analysis, BET/BJH nitrogen sorption, electron microscopy (REM and TEM) and EDX. With the latter methods we were able to demonstrate the homogenous distribution of the Pt(II) compound on and in the silica particles, and no Pt(II) bulk precipitate had formed. The in vitro cytotoxicity in a human cancer cell line (HeLa) has been determined for one of the new platinum compounds adsorbed to mesoporous silica particles of different size, and compared with the corresponding compound in solution. The IC50 data are similar in all cases, suggesting that the release of the Pt(II) compound was relatively fast and possibly occurred before the particles reached the cells. Overall, the platinum drug is chemically stable on silica and retained its activity upon prolonged storage.

Keywords: cytotoxicity, mesoporous silica, nanoparticles, platinum compounds

Procedia PDF Downloads 321

Authors: Angelis P. Barlampas, Ghita Bianca-Andreea

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A case of a prostatic midline cyst is presented, which was found during a routine general ultrasound examination in an otherwise healthy young man. The incidence of prostatic cysts discovered in suprapubic ultrasound examination has constantly been rising over the previous decades. Despite the fact that the majority of them are benign, a significant amount is related to symptoms, such as pain, dysuria, infertility, and even cancer. The wide use of ultrasound examination and the increasing availability of high-resolution ultrasound systems have rendered new diagnostic challenges. Once upon a time a suprapubic ultrasound was only useful for measuring only the size and the dimensions of the prostatic gland. It did not have the ability to analyze and resolve structures such as cystic or solid nodules. The current machine equipment has managed to depict the imaging characteristics of lesions with high acuity that compares of an intrarectal ultrasound. But the last one is a specialized examination, which demands expertise and good knowledge. Maybe the time has come for the general radiologist and, especially the one who uses suprapubic ultrasound, to pay more attention to the examination of the prostate gland and to take advantage of the superb abilities and the high resolution of the new ultrasound systems. That is exactly, what this case is emphasizing. The incidental discovery of prostatic cysts, and the relatively little available literature about managing them turns them into an interesting theme for exploring and studying. The prostatic cysts are further divided into midline and paramidline cysts, with the first being usually utricle cysts. A more precise categorization is as follows: A midline cystic lesion usually regards a Mullerian duct cyst, a prostatic utricle cyst, an ejaculatory duct cyst, a prostatic cystadenoma, a ductus deferens cyst, and a TURP. On the other hand, a lateral cystic lesion usually refers to a cystic degeneration of benign prostatic hyperplasia, a prostatic retention cyst, a seminal vesicle cyst, diverticular prostatitis, a prostatic abscess, cavitatory prostatitis from chronic prostatitis, a parasitic prostatic cyst, a cystic prostatic carcinoma, e.t.c.

Keywords: prostatic cyst, radiology, benign prostatic lesions, prostatic cancer, suprapubic prostatic ultrasound

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Authors: Christopher Leung, Tony Kim, Rebecca Lendzion, Scott Mackenzie

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Retroperitoneal abscesses are a rare but serious condition with often delayed diagnosis, non-specific symptoms, multiple causes and high morbidity/mortality. With the advent of more readily available cross-sectional imaging, retroperitoneal abscesses are treated earlier and better outcomes are achieved. Occasionally, a retroperitoneal abscess is present as a huge retroperitoneal abscess, as evident in this 53-year-old male. With a background of chronic renal disease and left partial nephrectomy, this gentleman presented with a one-month history of left flank pain without any other symptoms, including fevers or abdominal pain. CT abdomen and pelvis demonstrated a huge retroperitoneal abscess spanning from the diaphragm, abutting the spleen, down to the iliopsoas muscle and abutting the iliac vessels at the pelvic brim. This large retroperitoneal abscess required open drainage as well as drainage by interventional radiology. A long course of intravenous antibiotics and multiple drainages was required to drain the abscess. His blood culture and fluid culture grew Proteus species suggesting a urinary source, likely from his non-functioning kidney, which had a partial nephrectomy. Such a huge retroperitoneal abscess has rarely been described in the literature. The learning point here is that the basic principle of source control and antibiotics is paramount in treating retroperitoneal abscesses regardless of the size of the abscess.

Keywords: retroperitoneal abscess, retroperitoneal mass, sepsis, genitourinary infection

Procedia PDF Downloads 221

Authors: Wafa Toumi, Alessandro Ripalti, Luigi Ricciardiello, Dalila Gargouri, Jamel Kharrat, Abderraouf Cherif, Ahmed Bouhafa, Slim Jarboui, Mohamed Zili, Ridha Khelifa

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Background & aims: Colorectal cancer (CRC) is one of the most common malignancies throughout the world. Several risk factors, both genetic and environmental, including viral infections, have been linked to colorectal carcinogenesis. A few studies report the detection of human polyomavirus JC (JCV) DNA and transformation antigen (T-Ag) in a fraction of the colorectal tumors studied and suggest an association of this virus with CRC. In order to investigate whether such an association of JCV with CRC will hold in a different epidemiological setting, we looked for the presence of JCV DNA and T-Ag expression in a group of Tunisian CRC patients. Methods: Fresh colorectal mucosa biopsies were obtained from 17 healthy volunteers and from both colorectal tumors and adjacent normal tissues of 47 CRC patients. DNA was extracted from fresh biopsies or from formalin-fixed, paraffin-embedded tissue sections using the Invitrogen Purelink Genomic DNA mini Kit. A simple PCR and a nested PCR were used to amplify a region of the T-Ag gene. The obtained PCR products revealed a 154 bp and a 98 bp bands, respectively. Specificity was confirmed by sequencing of the PCR products. T-Ag expression was determined by immunohistochemical staining using a mouse monoclonal antibody (clone PAb416) directed against SV40 T-Ag that cross reacts with JCV T-Ag. Results: JCV DNA was found in 12 (25%) and 22 (46%) of the CRC tumors by simple PCR and by nested PCR, respectively. All paired adjacent normal mucosa biopsies were negative for viral DNA. Sequencing of the DNA amplicons obtained confirmed the authenticity of T-Ag sequences. Immunohistochemical staining showed nuclear T-Ag expression in all 22 JCV DNA- positive samples and in 3 additional tumor samples which appeared DNA-negative by PCR. Conclusions: These results suggest an association of JCV with a subpopulation of Tunisian colorectal tumors.

Keywords: colorectal cancer, immunohistochemistry, Polyomavirus JC, PCR

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Authors: Khaled. M.Benelhaj, Moada Elbadary

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The present investigation is carried out to evaluate the effect of aqueous extract of Arbutus Pavarii (Shemari) Libyan medical plant on ethylene glycol(EG) induce lithiasis in adult male albino rats. The lithiasis was induced to rats by oral administration of EG (0.75 w/v%) for 21 days(group 1). Aqueous extract of Shemari (200 mg/kg) was given orally from 1st day for preventive regimen (group 2) and from day 21st up to 42nd day for curative regimen (group 3). The results indicated that the EG elevated the urinary ionic of calcium, oxalates and inorganic phosphate. The Shemari significantly (P<0.01) reduced the levels of these ions. The histopathological findings showed that EG caused marked pathological changes in renal cortex; necrosis of glomerular tufts; mildy thickened bowman’s capsule and coagulative necrosis of large number of convoluted tubules. However, the histological changes in preventive regimen group 2 showed the same changes observed in group 1, but milder in severity and less in frequency. It conclude that Shemari do reduce the urinary ionic levels of calcium, oxalates and inorganic phosphate but failed to prevent complete deterioration effects of EG on kidney structures.

Keywords: EG, shamari, kidney stone, Libyan medical plant, glycol, oxalates

Procedia PDF Downloads 549

Authors: Ali Babaei Zarch, S. Kianbakht, H. Fallah Huseini, P. Changaei, A. Mirjalili, J. Salehi

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Background: Malva sylvestris L. is widely used in the traditional medicine of Iran and other countries to treat gastrointestinal, respiratory, skin and urological Disorders. Moreover, it has antioxidant property. Objective: In this study the protective effect of Malva sylvestris against sodium fluoride-induced nephrotoxicity in rats were evaluated. Methods: The Malva sylvestris flower extract was injected intraperitoneally at the doses of 100, 200, 400 mg/kg/day to groups of rats ( 10 in each group) for 1 week and subsequently 600 ppm sodium fluoride was added daily to the rats drinking water for 1 additional week. After these steps, the rats’ serum levels of urea, creatinine, reduced glutathione, catalase and malondialdehyde were determined. The histopathology of the rats’ kidney was also studied. Results: Malva sylvesteries extract with doses of 400 mg/kg/day significantly decreased the urea and creatinine levels (P<0.05). Moreover, the levels of catalase and glutathione were increased by this dose, but only the catalase increase was statistically significant (P<0.05). All three extract doses of Malva decreased the malondialdehyde level, but it was significant only for the dose 400 mg/kg/day (P<0.05). Histopathological findings also showed a protective effect of Malva against renal damage induced by sodium fluoride. Conclusion: The results suggest that Malva sylvestris has a protective effect against sodium fluoride-induced nephrotoxicity through its antioxidant property.

Keywords: Malva sylvestris, mephrotoxicity, sodium fluoride, rat  

Procedia PDF Downloads 337

Authors: Max Butler

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Melanoma accounts for 80% of skin cancer-related deaths globally. The poor prognosis and increasing incidence of melanoma impose a significant burden on global healthcare systems. Early detection, precise diagnosis, and preventative strategies are critical to improving patient outcomes. Dermoscopy is the gold standard for specialist assessments of pigmented skin lesions, as it can differentiate between benign and malignant growths with greater accuracy than visual inspection. In the United Kingdom, guidelines from the National Institute of Clinical Excellence (NICE) state dermoscopy should be used in all specialist assessments of pigmented skin lesions. Compliance with this guideline is low, resulting in missed and delayed melanoma diagnoses. To address this problem, a quality improvement project was initiated at Buckinghamshire Healthcare Trust (BHT) within the plastic surgery department. The target group was a trainee and consultant plastic surgeons conducting outpatient skin cancer clinics. Analysis of clinic documentation over a one-month period found that only 62% (38/61) of patients referred with pigmented skin lesions were examined using dermoscopy. To increase dermoscopy rates, teaching was delivered to the department highlighting national guidelines and the evidence base for dermoscopic examination. In addition, clinic paperwork was redesigned to include a text box for dermoscopic examination. Reauditing after the intervention found a significant increase in dermoscopy rates (52/61, p = 0.014). In conclusion, implementing a quality improvement project with targeted teaching and documentation template templates successfully increased dermoscopy rates. This is a promising step toward improving early melanoma detection and patient outcomes.

Keywords: melanoma, dermoscopy, plastic surgery, quality improvement

Procedia PDF Downloads 70

Authors: Keigo Nishitani, Kohei Mizuta Mizuta, Kazuyoshi Kurita, Yukinori Taniguchi

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To establish mass production process of Ti capsule which has Fe powder inside as magnetic hyperthermia implant, we assumed that Ti thin sheet can be drawn into a φ1.0 mm die hole through the medium of Fe Powder and becomes outer shell of capsule. This study discusses mechanism of powder assisted deep drawing process by both of numerical simulation and experiment. Ti thin sheet blank was placed on die, and was covered by Fe powder layer without pressurizing. Then upper punch was indented on the Fe powder layer, and the blank can be drawn into die cavity as pressurized powder particles were extruded into die cavity from behind of the drawn blank. Distinct Element Method (DEM) has been used to demonstrate the process. To identify bonding parameters on Fe particles which are cohesion, tensile bond stress and inter particle friction angle, axial and diametrical compression failure test of Fe powder compact was conducted. Several density ratios of powder compacts in range of 0.70 - 0.85 were investigated and relationship between mean stress and equivalent stress was calculated with consideration of critical state line which rules failure criterion in consolidation of Fe powder. Since variation of bonding parameters with density ratio has been experimentally identified, and good agreement has been recognized between several failure tests and its simulation, demonstration of powder assisted sheet forming by using DEM becomes applicable. Results of simulation indicated that indent/drawing length of Ti thin sheet is promoted by smaller Fe particle size, larger indent punch diameter, lower friction coefficient between die surface and Ti sheet and certain degrees of die inlet taper angle. In the deep drawing test, we have made die-set with φ2.4 mm punch and φ1.0 mm die bore diameter. Pure Ti sheet with 100 μm thickness, annealed at 650 deg. C has been tested. After indentation, indented/drawn capsule has been observed by microscope, and its length was measured to discuss the feasibility of this capsulation process. Longer drawing length exists on progressive loading pass comparing with the case of single stroke loading. It is expected that progressive loading has an advantage of which extrusion of powder particle into die cavity with Ti sheet is promoted since powder particle layer can be rebuilt while the punch is withdrawn from the layer in each loading steps. This capsulation phenomenon is qualitatively demonstrated by DEM simulation. Finally, we have fabricated Ti capsule which has Fe powder inside for magnetic hyperthermia cancer care treatment. It is concluded that suggested method is possible to use the manufacturing of Ti capsule implant for magnetic hyperthermia cancer care.

Keywords: metal powder compaction, metal forming, distinct element method, cancer care, magnetic hyperthermia

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Authors: Hossain A., Chowdhury S. I.

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Introduction: The use of a gamma camera is a standard procedure in nuclear medicine facilities or hospitals to diagnose chronic kidney disease (CKD), but the gamma camera does not precisely stage the disease. The authors sought to determine whether they could use an artificial neural network to determine whether CKD was in normal or abnormal stages based on GFR values (ANN). Method: The 250 kidney patients (Training 188, Testing 62) who underwent an ultrasonography test to diagnose a renal test in our nuclear medical center were scanned using a gamma camera. Before the scanning procedure, the patients received an injection of ⁹⁹ᵐTc-DTPA. The gamma camera computes the pre- and post-syringe radioactive counts after the injection has been pushed into the patient's vein. The artificial neural network uses the softmax function with cross-entropy loss to determine whether CKD is normal or abnormal based on the GFR value in the output layer. Results: The proposed ANN model had a 99.20 % accuracy according to K-fold cross-validation. The sensitivity and specificity were 99.10 and 99.20 %, respectively. AUC was 0.994. Conclusion: The proposed model can distinguish between normal and abnormal stages of CKD by using an artificial neural network. The gamma camera could be upgraded to diagnose normal or abnormal stages of CKD with an appropriate GFR value following the clinical application of the proposed model.

Keywords: artificial neural network, glomerular filtration rate, stages of the kidney, gamma camera

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Authors: Ayedun Hassan, Ayadi Odunayo Peter

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The ancient city of Abeokuta has been supplied with pipe borne water since 1911, yet, a continuous increase in population and unplanned city expansion makes water a very precious and scarce commodity. The government reserved areas (GRA’s) are well planned, and public water supply is available; however, the sub-urban areas consist of scattered structures with individuals trying to source water by digging wells and boreholes. The geology of the city consists of basement rock which makes digging wells and boreholes very difficult. The present study was conducted to assess the risk arising from the consumption of toxic elements in the groundwater of Abeokuta, Ogun State, Nigeria. Forty-five groundwater samples were collected from nine different areas of Abeokuta and analyzed for physicochemical parameters and toxic elements. The physicochemical parameters were determined using standard methods, while the toxic elements were determined using Inductively Coupled Plasma-Mass Spectrometer (ICP/MS). Ninety-six percent (96%) of the water sample has pH < 6.5, and 11% has conductivity > 250 µSCm⁻¹ limits in drinking water as recommended by WHO. Seven percent (7%) of the samples have Pb concentration >10 µgL⁻¹ while 75% have Al concentration >200 µgL⁻¹ recommended by WHO. The order for risk of cancer from different area of Abeokuta are Cd²⁺ > As³⁺ > Pb²⁺ > Cr⁶⁺ for Funaab, Camp and Obantoko; As³⁺ > Cd²⁺ > Pb²⁺ > Cr⁶⁺ for Ita Osin, Isale Igbein, Ake and Itoku; Cd²⁺ >As > Cr⁶⁺ > Pb²⁺ for Totoro; Pb²⁺ > Cd²⁺ > As³⁺ > Cr⁶⁺ for Idiaba. The order of non-cancer hazard index (HI) calculated for groundwater of Abeokuta City are Cd²⁺ > As³⁺ > Mn²⁺ > Pb²⁺ > Ni²⁺ and were all greater than one, which implies susceptibility to other illnesses. The sources of these elements are the rock and inappropriate waste disposal method, which leached the elements into the groundwater. A combination of sources from food will accumulate these elements in the human body system. Treatment to remove Al and Pb is necessary, while the method of water distribution should be reviewed to ensure access to potable water by the residents.

Keywords: Abeokuta, groundwater, Nigeria, risk

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Authors: Lukasz Szymanski, Zbigniew Kolacinski, Grzegorz Raniszewski, Slawomir Wiak, Lukasz Pietrzak, Dariusz Koza, Karolina Przybylowska-Sygut, Ireneusz Majsterek, Zbigniew Kaminski, Justyna Fraczyk, Malgorzata Walczak, Beata Kolasinska, Adam Bednarek, Joanna Konka

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The aim of this work is to investigate the influence of electromagnetic field from the range of radio frequencies on the desired nanoparticles for cancer therapy. In the article, the development and demonstration of the method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nanocontainers. The methodology of the production carbon - ferromagnetic nanocontainers (FNCs) includes: The synthesis of carbon nanotubes, chemical, and physical characterization, increasing the content of a ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. The ferromagnetic nanocontainers were synthesised in CVD and microwave plasma system. Biochemical functionalization of ferromagnetic nanocontainers is necessary in order to increase the binding selectively with receptors presented on the surface of tumour cells. Multi-step modification procedure was finally used to attach folic acid on the surface of ferromagnetic nanocontainers. Pristine ferromagnetic carbon nanotubes are not suitable for application in medicine and biotechnology. Appropriate functionalization of ferromagnetic carbon nanotubes allows to receiving materials useful in medicine. Finally, a product contains folic acids on the surface of FNCs. The folic acid is a ligand of folate receptors – α which is overexpressed on the surface of epithelial tumours cells. It is expected that folic acids will be recognized and selectively bound by receptors presented on the surface of tumour cells. In our research, FNCs were covalently functionalized in a multi-step procedure. Ferromagnetic carbon nanotubes were oxidated using different oxidative agents. For this purpose, strong acids such as HNO3, or mixture HNO3 and H2SO4 were used. Reactive carbonyl and carboxyl groups were formed on the open sides and at the defects on the sidewalls of FNCs. These groups allow further modification of FNCs as a reaction of amidation, reaction of introduction appropriate linkers which separate solid surface of FNCs and ligand (folic acid). In our studies, amino acid and peptide have been applied as ligands. The last step of chemical modification was reaction-condensation with folic acid. In all reaction as coupling reagents were used derivatives of 1,3,5-triazine. The first trials in the device for hyperthermal RF generator have been done. The frequency of RF generator was in the ranges from 10 to 14Mhz and from 265 to 621kHz. Obtained functionalized nanoparticles enabled to reach the temperature of denaturation tumor cells in given frequencies.

Keywords: cancer colon cells, carbon nanotubes, hyperthermia, ligands

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Authors: Vishnu Varthan Vaithiyalingamjagannathan, M. N. Sathishkumar, K. S. Lakhsmi, D. Satheeshkumar, Srividyaammayappanrajam

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Background:Naringenin, aglycone flavonoid possess certain activities like anti-oxidant, anti-estrogenic, anti-diabetic, cardioprotective, anti-obesity,anti-inflammatory, hepatoprotective and also have anti-cancer characteristics like carcinogenic inactivation, cell cycle arrest, anti-proliferation, apoptosis, anti-angiogenesis and enhances anti-oxidant activity. Methodology:The inhibitory effect of Naringenin in lung tumor progression estimated with adenocarcinoma (A549) cell lines (in vitro) and C57BL/6 mice injected with 5 X 106A549 cell lines (in vivo) in a tri-dose manner (Naringenin 100mg/kg,150mg/kg, and 200mg/kg) compared with standard chemotherapy drug cisplatin (7mg/kg). Results:The results of the present study revealed a dose-dependent activity in Naringenin and combination with cisplatin at a higher dose which showed decreased tumor progression in mice. In vitro studies carried out for estimation of cell survival and Nitric Oxide (NO) level, shows dose dependent action of Naringenin with IC50 value of 42µg/ml. In vivo studies were carried out in C57BL/6 mice. Naringenin satisfied the condition of an anti-cancer molecule with its characteristics in fragmentation assay, Zymography assay, anti-oxidant, and myeloperoxidase studies, than cisplatin which failed in anti-oxidant and myeloperoxidase effect. Both in vitro and in vivo establishes dose dependent decrease in NO levels. But whereas, Naringenin showed adverse results in Matrix Metalloproteinase (MMP) enzymatic levels with increase in dose levels. Conclusion:From the present study, Naringenin could suppress the lung tumor progression when given individually and also in combinatorial with standard chemotherapy drug.

Keywords: naringenin, in vitro, cell line, anticancer

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Authors: Kai-Yao Huang, Tzong-Yi Lee, Pin-Hao Ho, Tzu-Hao Chang, Cheng-Wei Chang

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Background: Human cytomegalovirus (HCMV) infects much people around the world, and there were many researches mention that many diseases were caused by HCMV. To understand the mechanism of HCMV lead to diseases during infection. We observe a microRNA (miRNA) – miRNA interaction between HCMV and host during infection. We found HCMV miRNA sequence component complementary with host miRNA precursors, and we also found that the host miRNA abundances were decrease in HCMV infection. Hence, we focus on the host miRNA which may target by the other HCMV miRNA to find theirs target mRNAs expression and analysis these mRNAs affect what kind of signaling pathway. Interestingly, we found the affected mRNA play an important role in some diseases related pathways, and these diseases had been annotated by HCMV infection. Results: From our analysis procedure, we found 464 human miRNAs might be targeted by 26 HCMV miRNAs and there were 291 human miRNAs shows the concordant decrease trend during HCMV infection. For case study, we found hcmv-miR-US22-5p may regulate hsa-mir-877 and we analysis the KEGG pathway which built by hsa-mir-877 validate target mRNA. Additionally, through survey KEGG Disease database found that these mRNA co-regulate some disease related pathway for instance cancer, nerve disease. However, there were studies annotated that HCMV infection casuse cancer and Alzheimer. Conclusions: This work supply a different scenario of miRNA target interactions(MTIs). In previous study assume miRNA only target to other mRNA. Here we wonder there is possibility that miRNAs might regulate non-mRNA targets, like other miRNAs. In this study, we not only consider the sequence similarity with HCMV miRNAs and human miRNA precursors but also the expression trend of these miRNAs. Then we analysis the human miRNAs validate target mRNAs and its associated KEGG pathway. Finally, we survey related works to validate our investigation.

Keywords: human cytomegalovirus, HCMV, microRNA, miRNA

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Authors: Petr Daniel Kovarik, Matt Kennedy, James Adams, Ajay Wilson, Andy Burns, Charles Kelly, Malcolm Jackson, Rahul Patil, Shahid Iqbal

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Introduction: Osteoradionecrosis (ORN) is a recognised toxicity of radiotherapy (RT) for head and neck cancer (HNC). Existing literature lacks any generally accepted definition and staging system for this toxicity. Objective: The objective is to analyse the outcome of the surgical and nonsurgical treatments of ORN. Material and Method: Data on 2303 patients treated for HNC with radical or adjuvant RT or RT-chemotherapy from January 2010 - December 2021 were retrospectively analysed. Median follow-up to the whole group of patients was 37 months (range 0–148 months). Results: ORN developed in 185 patients (8.1%). The location of ORN was as follows; mandible=170, maxilla=10, and extra oral cavity=5. Multiple ORNs developed in 7 patients. 5 patients with extra oral cavity ORN were excluded from treatment analysis as the management is different. In 180 patients with oral cavity ORN, median follow-up was 59 months (range 5–148 months). ORN healed in 106 patients, treatment failed in 74 patients (improving=10, stable=43, and deteriorating=21). Median healing time was 14 months (range 3-86 months). Notani staging is available in 158 patients with jaw ORN with no previous surgery to the mandible (Notani class I=56, Notani class II=27, and Notani class III=76). 28 ORN (mandible=27, maxilla=1; Notani class I=23, Notani II=3, Notani III=1) healed spontaneously with a median healing time 7 months (range 3–46 months). In 20 patients, ORN developed after dental extraction, in 1 patient in the neomandible after radical surgery as a part of the primary treatment. In 7 patients, ORN developed and spontaneously healed in irradiated bone with no previous surgical/dental intervention. Radical resection of the ORN (segmentectomy, hemi-mandibulectomy with fibula flap) was performed in 43 patients (all mandible; Notani II=1, Notani III=39, Notani class was not established in 3 patients as ORN developed in the neomandible). 27 patients healed (63%); 15 patients failed (improving=2, stable=5, deteriorating=8). The median time from resection to healing was 6 months (range 2–30 months). 109 patients (mandible=100, maxilla=9; Notani I=3, Notani II=23, Notani III=35, Notani class was not established in 9 patients as ORN developed in the maxilla/neomandible) were treated conservatively using a combination of debridement, antibiotics and Pentoclo. 50 patients healed (46%) with a median healing time 14 months (range 3–70 months), 59 patients are recorded with persistent ORN (improving=8, stable=38, deteriorating=13). Out of 109 patients treated conservatively, 13 patients were treated with Pentoclo only (all mandible; Notani I=6, Notani II=3, Notani III=3, 1 patient with neomandible). In total, 8 patients healed (61.5%), treatment failed in 5 patients (stable=4, deteriorating=1). Median healing time was 14 months (range 4–24 months). Extra orally (n=5), 3 cases of ORN were in the auditory canal and 2 in mastoid. ORN healed in one patient (auditory canal after 32 months. Treatment failed in 4 patients (improving=3, stable=1). Conclusion: The outcome of the treatment of ORN remains in general, poor. Every effort should therefore be made to minimise the risk of development of this devastating toxicity.

Keywords: head and neck cancer, radiotherapy, osteoradionecrosis, treatment outcome

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Authors: Mai M. Helmy

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Although the role of either nitric oxide (NO) or endothelin receptors modulation in the severity of cisplatin-induced nephrotoxicity has been recognized in previous studies including our own, the possible interaction between the two pathways remains obscure. In this study, we tested the possible interaction between the nitrergic and endothelin pathways in cisplatin-induced nephrotoxicity in male rats. Sprague Dawley male rats (200 to 250 g) were divided into four groups: Control (given a single dose of normal saline, i.p.), cisplatin (6 mg/kg, i.p.), cisplatin+Sildenafil (2 mg/kg, i.p.), cisplatin+Sildenafil+BQ-123 (1 mg/kg, i.p.). Each of the co-administered drugs was given in two doses; one hour before and one day after the cisplatin dose. Acute cisplatin administration resulted in significant increases in BUN and serum creatinine levels at 96 h following cisplatin injection. Increased levels of MDA, TNF-α and caspase-3, decreased nitrite/nitrate level and SOD activity in kidney homogenates were also observed following cisplatin injection. According to the obtained results, the co-adminstration of sildenafil alone with cisplatin offered a reno-protective effect comparable to that obtained following the concurrent administration of both sildenafil and the selective ETAR antagonist BQ-123. Thus, the current study is the first to reveal that the presence of an intact NO/cGMP system may offer a moderate reno-protective effect against cisplatin-induced nephrotoxicity even in the presence of ETAR-mediated vasoconstriction, suggesting the absence of obvious functional interaction between the nitrergic and endothelin pathways in cisplatin-induced nephrotoxicity in male rats.

Keywords: BQ-123, cisplatin, endothelin-1, nephrotoxicity, sildenafil

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Authors: Genesis Julyus T. Agcaoili, Esperanza C. Cabrera

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Thirty (30) isolates of lactic acid bacteria (LAB) from traditionally-prepared fermented products specifically fermented soy-bean paste, fermented mustard and fermented rice-fish mixture were studied for their in vitro antimicrobial and cytotoxic activities. Seventeen (17) isolates were identified as Lactobacillus plantarum, while 13 isolates were identified as Enterococcus spp using 16s rDNA sequences. Disc diffusion method was used to determine the antibacterial activity of LAB against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922), while the modified agar overlay method was used to determine the antifungal activity of LAB isolates on the yeast Candida albicans, and the dermatophytes Microsporum gypseum, Trichophyton rubrum and Epidermophyton floccosum. The filter-sterilized LAB supernatants were evaluated for their cytotoxicity to mammalian colon cancer cell lines (HT-29 and HCT116) and normal human dermal fibrolasts (HDFn) using resazurin assay (PrestoBlueTM). Colchicine was the positive control. No antimicrobial activity was observed against the bacterial test organisms and the yeast Candida albicans. On the other hand, all of the tested LAB strains were fungicidal for all the test dermatophytes. Cytotoxicity index profiles of the supernatants of the 15 randomly picked LABs and negative control (brain heart infussion broth) suggest nontoxicity to the cells when compared to colchicine, whereas all LAB supernatants were found to be cytotoxic to HT-29 and HCT116 colon cancer cell lines. Results provide strong support for the role of the lactic acid bacteria studied in antimicrobial treatment and anticancer therapy.

Keywords: antimicrobial, fermented products, fungicidal activity, lactic acid bacteria, probiotics

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Authors: Murali Aarthy, Sanjeev Kumar Singh

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High risk human papillomaviruses are highly associated with the carcinoma of the cervix and the other genital tumors. Cervical cancer develops through the multistep process in which increasingly severe premalignant dysplastic lesions called cervical intraepithelial neoplastic progress to invasive cancer. The oncoprotein E7 of human papillomavirus expressed in the lower epithelial layers drives the cells into S-phase creating an environment conducive for viral genome replication and cell proliferation. The replication of the virus occurs in the terminally differentiating epithelium and requires the activation of cellular DNA replication proteins. To date, no suitable drug molecule is available to treat HPV infection whereas identification of potential drug targets and development of novel anti-HPV chemotherapies with unique mode of actions are expected. Hence, our present study aimed to identify the potential inhibitors analogous to EGCG, a green tea molecule which is considered to be safe to use for mammalian systems. A 3D similarity search on the natural small molecule library from natural product database using EGCG identified 11 potential hits based on their similarity score. The structure based docking strategies were implemented in the potential hits and the key interacting residues of protein with compounds were identified through simulation studies and binding free energy calculations. The conformational changes between the apoprotein and the complex were analyzed with the simulation and the results demonstrated that the dynamical and structural effects observed in the protein were induced by the compounds and indicated the dominance to the oncoprotein. Overall, our study provides the basis for the structural insights of the identified potential hits and EGCG and hence, the analogous compounds identified can be potent inhibitors against the HPV 16 E7 oncoprotein.

Keywords: EGCG, oncoprotein, molecular dynamics simulation, analogues

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Authors: Nadine Wiesmann, Melanie Viel, Christoph Buhr, Rachel Tanner, Wolfgang Tremel, Juergen Brieger

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Recidivation of tumors and the development of resistances against the classical anti-tumor approaches represent a major challenge we face when treating cancer. In order to master this challenge, we are in desperate need of new treatment options beyond the beaten tracks. Zinc oxide nanoparticles (ZnO NPs) represent such an innovative approach. Zinc oxide is characterized by a high level of biocompatibility, concurrently ZnO NPs are able to exert anti-tumor effects. By concentration of the nanoparticles at the tumor site, tumor cells can specifically be exposed to the nanoparticles while low zinc concentrations at off-target sites are tolerated well and can be excreted easily. We evaluated the toxicity of ZnO NPs in vitro with the help of immortalized tumor cell lines and primary cells stemming from healthy tissue. Additionally, the Chorioallantoic Membrane Assay (CAM Assay) was employed to gain insights into the in vivo behavior of the nanoparticles. We could show that ZnO NPs interact with tumor cells as nanoparticulate matter. Furthermore, the extensive release of zinc ions from the nanoparticles nearby and within the tumor cells results in overload with zinc. Beyond that, ZnO NPs were found to further the generation of reactive oxygen species (ROS). We were able to show that tumor cells were more prone to the toxic effects of ZnO NPs at intermediate concentrations compared to fibroblasts. With the help of ZnO NPs covered by a silica shell in which FITC dye was incorporated, we were able to track ZnO NPs within tumor cells as well as within a whole organism in the CAM assay after injection into the bloodstream. Depending on the applied concentrations, selective tumor cell killing seems feasible. Furthermore, the combinational treatment of tumor cells with radiotherapy and ZnO NPs shows promising results. Still, further investigations are needed to gain a better understanding of the interaction between ZnO NPs and the human body to be able to pave the way for their application as an innovative anti-tumor agent in the clinics.

Keywords: metal oxide nanoparticles, nanomedicine, overcome resistances against classical treatment options, zinc oxide nanoparticles

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Authors: Katarína Koňariková, Georgios A. Perdikaris, Lucia Andrezálová, Zdeňka Ďuračková, Lucia Laubertová, Helena Gbelcová, Ingrid Žitňanová

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Introduction: The continuous demand for new anti-cancer drugs has stimulated chemotherapeutic research based on the use of essential metalloelements with the aim to develop potential drugs with lower toxicity and higher antiproliferative activity against tumors. Copper(II) and its complexes play an important role as suitable species for antiproliferative tests. Objectives: The central objective of the current study was to investigate the potential in vitro anti-proliferative effects of N-salicylidene-L-glutamato copper (II) complexes and molecular mechanism of apoptosis induced by tested complexes. In our project we tested N-salicylidene-L-glutamato copper (II) complexes ZK1 - [Cu(N-salicylidene-L-glutamato)(H2O)2].H2O; MK0 - ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O); MK1 - [Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O; MK3 - transbis(ethanol)tetrakis(imidazol)Cu(II)(2+)bis(N-salicylidene-D,L-glutamato-N,O)-KO:KO´-(imidazol); MK5 - [Cu(N-salicylidene-D,L- glutamato)(2-methylimidazol] at concentration range 0.001-100 µmol/L against human colon carcinoma cell line HT-29 and human breast carcinoma cell line MCF-7. Methods: Viability was assessed by direct counting of 0.4% trypan blue dye-excluding cells after 24, 48 and 72 hour cultivations with or without copper complex and by MTT assay. To analyze the type of cell death and its mechanism induced by our copper complex we used different methods. To distinguish apoptosis from necrosis we used electrophoretic analysis, to study the activity of caspases 8 and 9 – luminometric analysis and caspase activity 3 colorimetric assay. Results: The observed anti-proliferative effect of the copper complexes appeared to be dose-, time- and cell line- dependent. Human colon carcinoma cells HT-29 appeared to be more sensitive to the complex MK0 ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O) than to ZK1 ([Cu(N-salicylidene-L-glutamato)(H2O)2].H2O) and MK1 ([Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O)). Human colon carcinoma cells HT-29 appeared to be more sensitive to the complex than human breast carcinoma cells MCF-7. IC50 decreased with time of incubation (24, 48 and 72h) for HT-29, but increased for MCF-7. By electrophoresis we found apoptotic cell death induced by our copper complexes in HT-29 at concentrations 1, 10, 50 and 100 µmol/L after 48h (ZK1) and 72h (MK0, MK1) and in MCF-7 we did not find apoptosis. We also studied molecular mechanism of apoptosis in HT-29 induced by copper complexes. We found active caspase 9 in HT-29 after ZK1 ([Cu(N-salicylidene-L-glutamato)(H2O)2].H2O) and MK1 ([Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O)) influence and active caspase 8 after MK0 ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O) influence. Conclusion: Our copper complexes showed cytotoxic activities against human colon carcinoma cells HT-29 and breast cancer cell line MCF-7 in vitro. Apoptosis was activated by mitochondrial pathway (intrinsic pathway) in case of ZK1 [Cu(N-salicylidene-L-glutamato)(H2O)2].H2O; MK1 [Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O; MK3 - transbis(ethanol)tetrakis(imidazol)Cu(II)(2+)bis(N-salicylidene-D,L-glutamato-N,O)-KO:KO´-(imidazol) and MK5 - [Cu(N-salicylidene-D,L- glutamato)(2-methylimidazol] copper complexes and by death receptors (extrinsic pathway) in case of MK0 [Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O copper complex in HT-29.

Keywords: apoptosis, copper complex, cancer, carcinoma cell line

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Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Javaid Irfan, Andreas G. Schätzlein, Ijeoma F Uchegbeu

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Development of efficient delivery system for hydrophobic drugs remains a major concern in chemotherapy. The objective of the current study was to develop polymeric drug-delivery system for etoposide from amphiphilic derivatives of glycol chitosan, capable to improve the pharmacokinetics and to reduce the adverse effects of etoposide due to various organic solvents used in commercial formulations for solubilisation of etoposide. As a promising carrier, amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxy succinimide and quaternisation to glycol chitosan backbone. To this end a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternisation into 13 kDa. Nano sized micelles prepared from this amphiphilic polymer had the capability to encapsulate up to 3 mg/ml etoposide. The pharmacokinetic results indicated that GCPQ based etoposide formulation transformed the biodistribution pattern. AUC 0.5-24 hr showed statistically significant difference in ETP-GCPQ vs. commercial preparation in liver (25 vs 70, p<0.001), spleen (27 vs. 36, P<0.05), lungs (42 vs. 136, p<0.001), kidneys (25 vs. 30, p<0.05) and brain (19 vs. 9,p<0.001). Using the hydrophobic fluorescent dye Nile red, we showed that micelles efficiently delivered their payload to MCF7 and A2780 cancer cells in-vitro and to A431 xenograft tumor in-vivo, suggesting these systems could deliver hydrophobic anti- cancer drugs such as etoposide to tumors. The pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drug after intravenous administration. GCPQ based formulations not only reduced side effects associated with current available formulations but also increased their transport through the biological barriers, thus making it a good delivery system.

Keywords: glycol chitosan, Nile red, micelles, etoposide, A431 xenografts

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Authors: Odunayo Christy Atewolara-Odule, Olapeju O. Aiyelaagbe

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The search for new natural anti-oxidants has grown tremendously over the years because reactive oxygen species (ROS) production and oxidative stress have been linked to a large number of human degenerative diseases, such as cancer, cardiovascular diseases, inflammation, and diabetes. Tapinanthus bangwensis, a parasitic plant commonly known as mistletoe belonging to the Loranthaceae family, is mostly employed traditionally to treat inflammation, cancer, diabetes, and hypertension to mention a few. In this study, air-dried pulverized leaves and stem of Tapinanthus bangwensis were successively extracted with n-hexane, ethyl acetate, and methanol to give the corresponding crude extracts. The extracts were purified by column chromatography and high-performance liquid chromatography to give the isolated compounds. Structural elucidation was done using mass spectrometry, Fourier transform infra-red, 1D and 2D NMR spectroscopy. The antioxidant activity of the compounds was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ascorbic acid as standard. Three compounds; Friedelin, Eudesmic acid (3,4,5-trimethoxybenzoic) and Methyl-3,4,5-trimethoxybenzoate were isolated from the extracts of Tapinanthus bangwensis. Friedelin was isolated from the ethyl acetate extract of the stem while the two other compounds were isolated from the methanol extract of the leaves. The percentages of free radical scavenging activities of the compounds are as follows: Friedelin, 73.69%, methyl-3,4,5-trimethoxybenzoate, 79.33% and eudesmic, 87.68% anti-oxidant activity which were quite comparable to 93.96% given by ascorbic acid. We are reporting, to our best knowledge, for the first time the occurrence of friedelin and eudesmic acid in Tapinanthus bangwensis. The high anti-oxidant activity of these compounds supports the use of this plant in the management of diabetes and hypertension as they will be useful in combating complications arising from the disease.

Keywords: column chromatography, eudesmic acid, friedelin, Tapinanthus bangwensis

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Authors: Sehrish Jalal, Choon-Mee Kim, Dong-Min Kim

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Background: Many pathogens causing hemorrhagic fevers of medical and veterinary importance have been identified and isolated from rodents in the Republic of Korea (ROK). Objective: We investigated the prevalence of emerging viruses causing hemorrhagic fevers, such as hemorrhagic fever with renal syndrome (HFRS), severe fever with thrombocytopenia syndrome (SFTS) and flaviviruses, from wild rodents. Methods: Striped field mice, Apodemus agrarius, (n=39) were captured during 2014-2015 in the south-west of ROK. Using molecular methods, lung samples were evaluated for SFTS virus, HFRS virus and flavivirus, and seropositivity was evaluated in the blood. Results: A high positive rate of Hantavirus (46.2%) was detected in A.agrarius lungs by reverse transcription-nested polymerase chain reaction (RT-N-PCR). The monthly prevalence of HFRS virus was 16.7% in October, 86.7% in November and 25% in August of the following year (p < 0.001). Moreover, 17.9% of blood samples were serologically positive for Hantavirus antibodies. The most prevalent strain in A. agrarius was Hantaan virus. All samples were positive for neither SFTS nor flavivirus. Conclusion: Hantan virus was detected in 86.7% of A. agrarius in November (autumn), and thus, virus shedding from A. agrarius can increase the risk of humans contracting HFRS. These findings may help to predict and prevent disease outbreaks in ROK.

Keywords: hemorrhagic fever virus, molecular diagnostic technique, rodents, Korea

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Authors: Andrea L. Arnett, Ann T. Packard, Yolanda I. Garces, Kenneth W. Merrell

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Objective: Pathologic response following neoadjuvant chemoradiation (CRT) has been associated with improved overall survival (OS). Conflicting results have been reported regarding the pathologic predictive value of positron emission tomography (PET) response in patients with stage III lung cancer. The aim of this study was to evaluate the correlation between post-treatment PET response and pathologic response utilizing novel FDG-PET parameters. Methods: This retrospective study included patients with non-metastatic, stage IIIA (N2) NSCLC cancer treated with CRT followed by resection. All patients underwent PET prior to and after neoadjuvant CRT. Univariate analysis was utilized to assess correlations between PET response, nodal clearance, pCR, and near-complete pathologic response (defined as the microscopic residual disease or less). Maximal standard uptake value (SUV), standard uptake ratio (SUR) [normalized independently to the liver (SUR-L) and blood pool (SUR-BP)], metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured pre- and post-chemoradiation. Results: A total of 44 patients were included for review. Median age was 61.9 years, and median follow-up was 2.6 years. Histologic subtypes included adenocarcinoma (72.2%) and squamous cell carcinoma (22.7%), and the majority of patients had the T2 disease (59.1%). The rate of pCR and near-complete pathologic response within the primary lesion was 28.9% and 44.4%, respectively. The average reduction in SUVmₐₓ was 9.2 units (range -1.9-32.8), and the majority of patients demonstrated some degree of favorable treatment response. SUR-BP and SUR-L showed a mean reduction of 4.7 units (range -0.1-17.3) and 3.5 units (range –1.7-12.6), respectively. Variation in PET response was not significantly associated with histologic subtype, concurrent chemotherapy type, stage, or radiation dose. No significant correlation was found between pathologic response and absolute change in MTV or TLG. Reduction in SUVmₐₓ and SUR were associated with increased rate of pathologic response (p ≤ 0.02). This correlation was not impacted by normalization of SUR to liver versus mediastinal blood pool. A threshold of > 75% decrease in SUR-L correlated with near-complete response, with a sensitivity of 57.9% and specificity of 85.7%, as well as positive and negative predictive values of 78.6% and 69.2%, respectively (diagnostic odds ratio [DOR]: 5.6, p=0.02). A threshold of >50% decrease in SUR was also significantly associated pathologic response (DOR 12.9, p=0.2), but specificity was substantially lower when utilizing this threshold value. No significant association was found between nodal PET parameters and pathologic nodal clearance. Conclusions: Our results suggest that treatment response to neoadjuvant therapy as assessed on PET imaging can be a predictor of pathologic response when evaluated via SUV and SUR. SUR parameters were associated with higher diagnostic odds ratios, suggesting improved predictive utility compared to SUVmₐₓ. MTV and TLG did not prove to be significant predictors of pathologic response but may warrant further investigation in a larger cohort of patients.

Keywords: lung cancer, positron emission tomography (PET), standard uptake ratio (SUR), standard uptake value (SUV)

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Authors: Armaghan Moravej Aleali, Seyed Mahmoud Latifi, Homeira Rashidi

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Objective: High blood pressure in a risk factor for some disease like stroke, coronary heart disease, and renal failure. High blood pressure in children is an increasing health problem. The aim of this present was to determine prevalence of hypertension and pre-hypertension age between 10 to 17 years old. Material & Methods: This descriptive-analytic study was conducted using multiphase sampling method in Ahvaz (Southwest of Iran). A questionnaire include: height, weight, and body mass index, systolic and diastolic blood pressures filled for each participant. Blood pressure was measured twice for each person. For the diagnosis of hypertension, the fourth report of the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents of the National Health Institute of United States was used. Results: The subject participants of the study were 1707children and adolescents including 922 boys (54%) and 785 girls 46%). The prevalence of high blood pressure was 1.7% (boys 2.5% girls 0.8%). The prevalence of pre-hypertension was 9 % (7.6% in boys, 10.6% in girls). The mean systolic and diastolic blood pressures increased with increasing body mass index. Conclusion: In this study, the prevalence of high blood pressure was found to be lower than other studies in our country. The prevalence of the high blood pressure in boys was significantly higher than girls. This study, like other studies, showed a high correlation between being overweight and an increase in systolic and diastolic blood pressure.

Keywords: hypertension, pre-hypertension, childhood, adolescence

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Authors: B. Medani Amna, M. A. Elbadwi Samia, E. Amin Ahmed

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Variable plants present in nature are used by simple rural and urban people, researchers and drug manufacturers for medicinal purposes. Garad is one of the most commonly used in Sudan for both treatment and prophylaxis of infections in the respiratory, urinogenital tracts and the skin. Water exctracts from Acacia nilotica bods were used in this very experiment to test for their toxicity to Nubian goats at two dose rates under proper experimental conditions. The clinical, pathological, haematological and biological changes in Nubian goats given daily oral doses of 1 and 5 g/kg body weight of Acacia nilotica to two groups of test goats. The goats of the control group were undosed with Acacia nilotica.Other than the dose co-related mortality rates, the clinical signs were observed to be salivation, staggered gait, intermittent loss of voice and low appetite. On histopathological testing, the main lesions were hepatic centrolobular necrosis and fatty changes associated with the significant changes in GGT and ALP are indicating hepatic dysfunction.Renal malfunction is indicated by haemorrhages in addition to the change in the urea concentration. The congested, haemorrhagic, emphysematous, edematous and cyanotic lungs may contribute to the development of dyspnea. Acacia nilotica poisoning may lead to an immunosuppression pointed out by the lymphocyte infiltration. On evaluation of the above results, Acacia nilotica was considered toxic to Nubian goats at the above mentioned doses. Future work for Acacia nilotica was forwarded and practical implications of the result were highlighted.

Keywords: Acaia nilotica, toxicity data, Nubian goats, Garad

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Authors: Michelle S. Pereira, Analice C. Azevedo, Julliane D. Medeiros, Ana Claudia S. Martins, Didier S. Castellano-Filho, Claudio G. Diniz, Vania L. Silva

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Vaginal microbiota is a complex ecosystem, composed by aerobic and anaerobic bacteria, living in a dynamic equilibrium. Lactobacillus spp. are predominant in vaginal ecosystem, and factors such as immunity and hormonal variations may lead to disruptions, resulting in proliferation of opportunistic pathogens. Bacterial vaginosis (BV) is a polymicrobial syndrome, caused by an increasing of anaerobic bacteria replacing Lactobacillus spp. Microorganisms such as Gardnerella vaginalis, Mycoplasma hominis, Mobiluncus spp., and Atopobium vaginae can be found in BV, which may also be associated to other infections such as by Human Papillomavirus (HPV). HPV is highly prevalent in sexually active women, and is considered a risk factor for development of cervical cancer. As long as few data is available on vaginal microbiota of women with HPV-associated cervical lesions, our objectives were to evaluate the diversity in vaginal ecosystem in these women. To all patients, clinical and socio-demographic data were collected after gynecological examination. This study was approved by the Ethics Committee from Federal University of Juiz de Fora, Minas Gerais, Brazil. Vaginal secretion and cervical scraping were collected. Gram-stained smears were evaluated to establish Nugent score for BV determination. Viral and bacterial DNA obtained was used as template for HPV genotyping (PCR) and bacterial fingerprint (REP-PCR). In total 31 patients were included (mean age 35 and 93.6% sexually active). The Nugent score showed that 38.7% were BV. From the medical records, Pap smear tests showed that 32.3% had low grade squamous epithelial lesion (LSIL), 29% had high grade squamous epithelial lesion (HSIL), 25.8% had atypical squamous cells of undetermined significance (ASC-US) and 12.9% with atypical squamous cells that would not exclude high-grade lesion (ASC-H). All participants were HPV+. HPV-16 was the most frequent (87.1%), followed by HPV-18 (61.3%). HPV-31, HPV-52 and HPV-58 were also detected. Coinfection HPV-16/HPV-18 was observed in 75%. In the 18-30 age group, HPV-16 was detected in 40%, and HPV-16/HPV-18 coinfection in 35%. HPV-16 was associated to 30% of ASC-H and 20% of HSIL patients. BV was observed in 50% of HPV-16+ participants and in 45% of HPV-16/HPV-18+. Fingerprints of bacterial communities showed clusters with low similarity suggesting high heterogeneity in vaginal microbiota within the sampled group. Overall, the data is worrisome once cervical-cancer highly risk-associated HPV-types were identified. The high microbial diversity observed may be related to the different levels of cellular lesions, and different physiological conditions of the participants (age, social behavior, education). Further prospective studies are needed to better address correlations and BV and microbial imbalance in vaginal ecosystems which would be related to the different cellular lesions in women with HPV infections. Supported by FAPEMIG, CNPq, CAPES, PPGCBIO/UFJF.

Keywords: human papillomavirus, bacterial vaginosis, bacterial diversity, cervical cancer

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