Search results for: therapeutic results
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 37032

Search results for: therapeutic results

36042 Comparative Scanning Electron Microscopic Observations of Anthelminthic Effect of Trigonella foenum-graecum on Paramphistomum cervi in Buffalo

Authors: Kiran Roat, Bhanupriya Sanger, Gayatri Swarnakar

Abstract:

Amphistomiasis disease is the main health problem throughout of the world and responsible for great economic losses to cattle industries, mostly to poor cattle farmers in developing countries. Among the rumen parasites, the Paramphistomum cervi were collected from the rumen of freshly slaughtered buffalo for the further treatment process. Trigonella foenum-graecum is commonly known as methi and fenugreek and their seeds are known for their therapeutic value. The present study was considered to evaluate in vitro efficacy of aqueous extract of Trigonella foenum-graecum on P. cervi. 130 mg/ml concentration of aqueous extract shows total mortality of P. cervi at 5 hours. The ultrastructural surface topography of untreated animal was compared with a treated animal by scanning electron microscope (SEM). The body of untreated P. cervi in conical shape, tegumental surface is highly ridged with transverse folds and present abundance number of papillaes. Observations demonstrated that the body of treated P. cervi become shrunken & elongated. Treated parasite shows the deep breakage in tegument and the disappearance of tegumental folds & papillae. Severe blebs formations have been found. Above findings, it can be concluded that the seeds of Trigonella foenum-graecum can be used as an anthelminthic agent to eliminate P. cervi from the body of buffalo.

Keywords: Paramphistomum cervi, Trigonella foenum-graecum, scanning electron microscope, buffalo

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36041 Numerical and Experimental Investigations of Cantilever Rectangular Plate Structure on Subsonic Flutter

Authors: Mevlüt Burak Dalmış, Kemal Yaman

Abstract:

In this study, flutter characteristics of cantilever rectangular plate structure under incompressible flow regime are investigated by comparing the results of commercial flutter analysis program ZAERO© with wind tunnel tests conducted in Ankara Wind Tunnel (ART). A rectangular polycarbonate (PC) plate, 5x125x1000 mm in dimensions, is used for both numerical and experimental investigations. Analysis and test results are very compatible with each other. A comparison between two different solution methods (g and k-method) of ZAERO© is also done. It is seen that, k-method gives closer result than the other one. However, g-method results are on conservative side and it is better to use conservative results namely g-method results. Even if the modal analysis results are used for the flutter analysis for this simple structure, a modal test should be conducted in order to validate the modal analysis results to have accurate flutter analysis results for more complicated structures.

Keywords: flutter, plate, subsonic flow, wind tunnel

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36040 Comparative Evaluation of Pharmacologically Guided Approaches (PGA) to Determine Maximum Recommended Starting Dose (MRSD) of Monoclonal Antibodies for First Clinical Trial

Authors: Ibraheem Husain, Abul Kalam Najmi, Karishma Chester

Abstract:

First-in-human (FIH) studies are a critical step in clinical development of any molecule that has shown therapeutic promise in preclinical evaluations, since preclinical research and safety studies into clinical development is a crucial step for successful development of monoclonal antibodies for guidance in pharmaceutical industry for the treatment of human diseases. Therefore, comparison between USFDA and nine pharmacologically guided approaches (PGA) (simple allometry, maximum life span potential, brain weight, rule of exponent (ROE), two species methods and one species methods) were made to determine maximum recommended starting dose (MRSD) for first in human clinical trials using four drugs namely Denosumab, Bevacizumab, Anakinra and Omalizumab. In our study, the predicted pharmacokinetic (pk) parameters and the estimated first-in-human dose of antibodies were compared with the observed human values. The study indicated that the clearance and volume of distribution of antibodies can be predicted with reasonable accuracy in human and a good estimate of first human dose can be obtained from the predicted human clearance and volume of distribution. A pictorial method evaluation chart was also developed based on fold errors for simultaneous evaluation of various methods.

Keywords: clinical pharmacology (CPH), clinical research (CRE), clinical trials (CTR), maximum recommended starting dose (MRSD), clearance and volume of distribution

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36039 Study of the Anti-Diabetic Activity of the Common Fig in the Region of the El Amra (Ain Defla), Algeria

Authors: Meliani Samiha, Hassaine Sarah

Abstract:

Figs are so much consumed in the Mediterranean region; they present a high nutritional value and also multiple therapeutic virtues. Our work contributes to the study of the antidiabetic activity of the common fig of the region of El Amra (AinDefla) Algeria. To do this, 20 Wistar rats female, divided into 4 lots, were used: Lot 1: 5 normal controls; Lot 2: 5 normal controls treated with dry fig juice at 20%; Lot 3: 5 diabetic controls; Lot 4: 5 diabetic controls treated with dry fig juice at 20%. The rats are rendered diabetic by intra-peritoneal injection of a streptozotocin solution. The blood glucose is measured after 1 hour, 2 hours, 3 hours and after 4 hours of the administration of the fig juice; it’s measured also on the 5th day, 8th day and 9th day of the beginning of the experiment. The determination of cholesterol and triglycerides blood is carried out at the beginning and the end of the study. On the 9th day, we recorded a very significant decrease of the blood sugar level of diabetic rats treated with dry fig juice. This blood glucose level normalized for 3 rats/5rats, we also recorded a decrease, but not significant, of cholesterol and triglycerides blood levels. In the short term (for 4 hours), an increase of blood sugar level, one hour after administration, for normal and diabetic rats. This increase is probably due to the high level of sugar content in the preparation. The blood glucose level is then corrected, four hours later. This may be the result of anti hyperglycemic effect of the active ingredients contained in the figs.

Keywords: antidiabetic, figs, hypoglycemia, streptozotocin

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36038 Sphingosomes: Potential Anti-Cancer Vectors for the Delivery of Doxorubicin

Authors: Brajesh Tiwari, Yuvraj Dangi, Abhishek Jain, Ashok Jain

Abstract:

The purpose of the investigation was to evaluate the potential of sphingosomes as nanoscale drug delivery units for site-specific delivery of anti-cancer agents. Doxorubicin Hydrochloride (DOX) was selected as a model anti-cancer agent. Sphingosomes were prepared and loaded with DOX and optimized for size and drug loading. The formulations were characterized by Malvern zeta-seizer and Transmission Electron Microscopy (TEM) studies. Sphingosomal formulations were further evaluated for in-vitro drug release study under various pH profiles. The in-vitro drug release study showed an initial rapid release of the drug followed by a slow controlled release. In vivo studies of optimized formulations and free drug were performed on albino rats for comparison of drug plasma concentration. The in- vivo study revealed that the prepared system enabled DOX to have had enhanced circulation time, longer half-life and lower elimination rate kinetics as compared to free drug. Further, it can be interpreted that the formulation would selectively enter highly porous mass of tumor cells and at the same time spare normal tissues. To summarize, the use of sphingosomes as carriers of anti-cancer drugs may prove to be a fascinating approach that would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.

Keywords: sphingosomes, anti-cancer, doxorubicin, formulation

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36037 A Method for Evaluating the Mechanical Stress on Mandibular Advancement Devices

Authors: Tsung-yin Lin, Yi-yu Lee, Ching-hua Hung

Abstract:

Snoring, the lay term for obstructive breathing during sleep, is one of the most prevalent of obnoxious human habits. Loud snoring usually makes others feel noisy and uncomfortable. Snoring also influences the sleep quality of snorers’ bed partners, because of the noise they do not get to sleep easily. Snoring causes the reduce of sleep quality leading to several medical problems, such as excessive daytime sleepiness, high blood pressure, increased risk for cardiovascular disease and cerebral vascular accident, and etc. There are many non-prescription devices offered for sale on the market, but very limited data are available to support a beneficial effect of these devices on snoring and use in treating obstructive sleep apnea (OSA). Mandibular advancement devices (MADs), also termed as the Mandibular reposition devices (MRDs) are removable devices which are worn at night during sleep. Most devices require dental impression, bite registration, and fabrication by a dental laboratory. Those devices are fixed to upper and lower teeth and are adjusted to advance the mandible. The amount of protrusion is adjusted to meet the therapeutic requirements, comfort, and tolerance. Many devices have a fixed degree of advancement. Some are adjustable in a limited degree. This study focuses on the stress analysis of Mandibular Advancement Devices (MADs), which are considered as a standard treatment of snoring that promoted by American Academy of Sleep Medicine (AASM). This paper proposes a new MAD design, and the finite element analysis (FEA) is introduced to precede the stress simulation for this MAD.

Keywords: finite element analysis, mandibular advancement devices, mechanical stress, snoring

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36036 Comparison of Polyphonic Profile of a Berry from Two Different Sources, Using an Optimized Extraction Method

Authors: G. Torabian, A. Fathi, P. Valtchev, F. Dehghani

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The superior polyphenol content of Sambucus nigra berries has high health potentials for the production of nutraceutical products. Numerous factors influence the polyphenol content of the final products including the berries’ source and the subsequent processing production steps. The aim of this study is to compare the polyphenol content of berries from two different sources and also to optimise the polyphenol extraction process from elderberries. Berries from source B obtained more acceptable physical properties than source A; a single berry from source B was double in size and weight (both wet and dry weight) compared with a source A berry. Despite the appropriate physical characteristics of source B berries, their polyphenolic profile was inferior; as source A berries had 2.3 fold higher total anthocyanin content, and nearly two times greater total phenolic content and total flavonoid content compared to source B. Moreover, the result of this study showed that almost 50 percent of the phenolic content of berries are entrapped within their skin and pulp that potentially cannot be extracted by press juicing. To address this challenge and to increase the total polyphenol yield of the extract, we used cold-shock blade grinding method to break the cell walls. The result of this study showed that using cultivars with higher phenolic content as well as using the whole fruit including juice, skin and pulp can increase polyphenol yield significantly; and thus, may boost the potential of using elderberries as therapeutic products.

Keywords: different sources, elderberry, grinding, juicing, polyphenols

Procedia PDF Downloads 280
36035 Glutharaldyde Free Processing of Patch for Cardiovascular Repair Is Associated with Improved Outcomes on Rvot Repair, Rat Model

Authors: Parnaz Boodagh, Danila Vella, Antonio Damore, Laura Modica De Mohac, Sang-Ho Ye, Garret Coyan, Gaetano Burriesci, William Wagner, Federica Cosentino

Abstract:

The use of cardiac patches is among the main therapeutic solution for cardiovascular diseases, a leading mortality cause in the world with an increasing trend, responsible of 19 millions deaths in 2020. Several classes of biomaterials serve that purpose, both of synthetic origin and biological derivation, and many bioengineered treatment alternatives were proposed to satisfy two main requirements, providing structural support and promoting tissue remodeling. The objective of this paper is to compare the mechanical properties and the characterization of four cardiac patches: the Adeka, PhotoFix, CorPatch, and CardioCel patches. In vitro and in vivo tests included: biaxial, uniaxial, ball burst, suture retention for mechanical characterization; 2D surface topography, 3D volume and microstructure, and histology assessments for structure characterization; in vitro test to evaluate platelet deposition, calcium deposition, and macrophage polarization; rat right ventricular outflow tract (RVOT) models at 8- and 16-week time points to characterize the patch-host interaction. Lastly, the four patches were used to produce four stented aortic valve prosthesis, subjected to hydrodynamic assessment as well as durability testing to verify compliance with the standard ISO.

Keywords: cardiac patch, cardiovascular disease, cardiac repair, blood contact biomaterial

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36034 Drug-Drug Plasma Protein Binding Interactions of Ivacaftor

Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

Abstract:

Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

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36033 Anti-Infective Potential of Selected Philippine Medicinal Plant Extracts against Multidrug-Resistant Bacteria

Authors: Demetrio L. Valle Jr., Juliana Janet M. Puzon, Windell L. Rivera

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From the various medicinal plants available in the Philippines, crude ethanol extracts of twelve (12) Philippine medicinal plants, namely: Senna alata L. Roxb. (akapulko), Psidium guajava L. (bayabas), Piper betle L. (ikmo), Vitex negundo L. (lagundi), Mitrephora lanotan (Blanco) Merr. (Lanotan), Zingiber officinale Roscoe (luya), Curcuma longa L. (Luyang dilaw), Tinospora rumphii Boerl (Makabuhay), Moringga oleifera Lam. (malunggay), Phyllanthus niruri L. (sampa-sampalukan), Centella asiatica (L.) Urban (takip kuhol), and Carmona retusa (Vahl) Masam (tsaang gubat) were studied. In vitro methods of evaluation against selected Gram-positive and Gram-negative multidrug-resistant (MDR), bacteria were performed on the plant extracts. Although five of the plants showed varying antagonistic activities against the test organisms, only Piper betle L. exhibited significant activities against both Gram-negative and Gram-positive multidrug-resistant bacteria, exhibiting wide zones of growth inhibition in the disk diffusion assay, and with the lowest concentrations of the extract required to inhibit the growth of the bacteria, as supported by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Further antibacterial studies of the Piper betle L. leaf, obtained by three extraction methods (ethanol, methanol, supercritical CO2), revealed similar inhibitory activities against a multitude of Gram-positive and Gram-negative MDR bacteria. Thin layer chromatography (TLC) assay of the leaf extract revealed a maximum of eight compounds with Rf values of 0.92, 0.86, 0.76, 0.53, 0.40, 0.25, 0.13, and 0.013, best visualized when inspected under UV-366 nm. TLC- agar overlay bioautography of the isolated compounds showed the compounds with Rf values of 0.86 and 0.13 having inhibitory activities against Gram-positive MDR bacteria (MRSA and VRE). The compound with an Rf value of 0.86 also possesses inhibitory activity against Gram-negative MDR bacteria (CRE Klebsiella pneumoniae and MBL Acinetobacter baumannii). Gas Chromatography-Mass Spectrometry (GC-MS) was able to identify six volatile compounds, four of which are new compounds that have not been mentioned in the medical literature. The chemical compounds isolated include 4-(2-propenyl)phenol and eugenol; and the new four compounds were ethyl diazoacetate, tris(trifluoromethyl)phosphine, heptafluorobutyrate, and 3-fluoro-2-propynenitrite. Phytochemical screening and investigation of its antioxidant, cytotoxic, possible hemolytic activities, and mechanisms of antibacterial activity were also done. The results showed that the local variant of Piper betle leaf extract possesses significant antioxidant, anti-cancer and antimicrobial properties, attributed to the presence of bioactive compounds, particularly of flavonoids (condensed tannin, leucoanthocyanin, gamma benzopyrone), anthraquinones, steroids/triterpenes and 2-deoxysugars. Piper betle L. is also traditionally known to enhance wound healing, which could be primarily due to its antioxidant, anti-inflammatory and antimicrobial activities. In vivo studies on mice using 2.5% and 5% of the ethanol leaf extract cream formulations in the excised wound models significantly increased the process of wound healing in the mice subjects, the results and values of which are at par with the current antibacterial cream (Mupirocin). From the results of the series of studies, we have definitely proven the value of Piper betle L. as a source of bioactive compounds that could be developed into therapeutic agents against MDR bacteria.

Keywords: Philippine herbal medicine, multidrug-resistant bacteria, Piper betle, TLC-bioautography

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36032 Effects of Ethanolic Purslane Shoot and Seed Extracts on Doxorubicin-Induced Hepatotoxicity in Albino Rats

Authors: Osama M. Ahmed, Walaa G. Hozayen, Haidy Tamer Abo Sree

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Doxorubicin (DOX), an anthracycline antibiotic is a broad-spectrum antineoplastic agent, which is commonly used in the treatment of uterine, ovarian, breast and lung cancers, Hodgkin's disease and soft tissue sarcomas as well as in several other cancer types. The effect of doxorubicin (4 mg/kg b.w.week) without or with oral administration of ethanolic purslane (Portulaca oleracea) shoot (leaves and stems) extract (50 mg/kg b.w. day) or ethanolic purslane seeds extract (50 mg/kg b.w.day) co-treatments for 6 weeks was evaluated in adult male rats. Serum ALT, AST, ALP, GGT, total bilirubin, total protein, and albumin levels were assayed. Lipid peroxidation (indexed by MDA) and antioxidants like hepatic glutathine, glutathione transferase, peroxidase, SOD, and CAT were assessed. There was an increase in serum levels of ALT, AST, ALP, GGT and total bilirubin. In addition, hepatic glutathine, glutathione transferase, peroxidase, SOD, and CAT activities were decreased while lipid peroxidation in the liver was increased. Co-administration of ethanolic purslane and seed extracts successfully improved the adverse changes in the liver functions with an increase in antioxidants activities and reduction of lipid peroxidation. In conclusion, it can be supposed that dietary purslane extract supplementation may provide a cushion for a prolonged therapeutic option against DOX hepatopathy without harmful side effects. However, further clinical studies are required to assess the safety and efficacy of these extract in human beings.

Keywords: doxorubicin, purslane, hepatotoxicity, antioxidants

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36031 Thermoluminescent Response of Nanocrystalline BaSO4:Eu to 85 MeV Carbon Beams

Authors: Shaila Bahl, S. P. Lochab, Pratik Kumar

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Nanotechnology and nanomaterials have attracted researchers from different fields, especially from the field of luminescence. Recent studies on various luminescent nanomaterials have shown their relevance in dosimetry of ionizing radiations for the measurements of high doses using the Thermoluminescence (TL) technique, where the conventional microcrystalline phosphors saturate. Ion beams have been used for diagnostic and therapeutic purposes due to their favorable profile of dose deposition at the end of the range known as the Bragg peak. While dealing with human beings, doses from these beams need to be measured with great precision and accuracy. Henceforth detailed investigations of suitable thermoluminescent dosimeters (TLD) for dose verification in ion beam irradiation are required. This paper investigates the TL response of nanocrystalline BaSO4 doped with Eu to 85 MeV carbon beam. The synthesis was done using Co-precipitation technique by mixing Barium chloride and ammonium sulphate solutions. To investigate the crystallinity and particle size, analytical techniques such as X-ray diffraction (XRD) and Transmission electron microscopy (TEM) were used which revealed the average particle sizes to 45 nm with orthorhombic structure. Samples in pellet form were irradiated by 85 MeV carbon beam in the fluence range of 1X1010-5X1013. TL glow curves of the irradiated samples show two prominent glow peaks at around 460 K and 495 K. The TL response is linear up to 1X1013 fluence after which saturation was observed. The wider linear TL response of nanocrystalline BaSO4: Eu and low fading make it a superior candidate as a dosimeter to be used for detecting the doses of carbon beam.

Keywords: radiation, dosimetry, carbon ions, thermoluminescence

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36030 Serum Sickness-Like Reaction to D-Mannose Supplement

Authors: Emma Plante, Charles Ekwunwa, Diego Illanes

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Introduction: Serum Sickness-Like Reaction (SSLR) is an inflammatory immune response characterized by a rash, polyarthralgias, and fever. SSLR usually occurs in response to a new medication (most commonly antibiotics, anticonvulsants, or antiinflammatory agents) and is believed to involve the formation of drug-specific immune complexes. Here we present a case of a 16-year-old female patient who developed an SSLR in response to the D-mannose-containing over-the-counter supplement, Uqora, used to promote bladder health. Methodology: The methodology for this study included a thorough literature search for other cases of SSLR associated with D-Mannose containing products. Data collection was performed through a review of the patient’s medical record, including history, physical examination, relevant laboratory results, and treatment plan. Findings: A 16-year-old female with a history of overactive bladder and anemia presented with a diffuse urticarial rash, headaches, joint pain, and swelling for three days. Her medications included oral contraceptive pills, iron, mirabegron, UQora, and a probiotic. Physical examination revealed a diffuse urticarial rash, and her musculoskeletal exam revealed swelling and tenderness in her wrists. Her CBC, basic metabolic panel, liver function panel, lyme titers, and urinalysis were all within normal limits. The patient was referred to an allergist, who diagnosed her with SSLR. All medications were discontinued, and she was treated with a 7-day course of prednisone and cetirizine. Her symptoms resolved, and her medications were slowly resumed sequentially over several months. However, UQora triggered a recurrence of her symptoms, and it was identified as the culprit medication. Consequently, UQora was permanently discontinued, and the patient has remained symptom-free. Conclusion: This case report describes the first documented case of SSLR caused by UQora (active ingredient D-mannose). D-Mannose is a monosaccharide found in many plants and fruits, and it is commonly used to prevent urinary tract infections. While the clinical features and timeline, in this case, were typical of SSLR, UQora as the trigger was highly unusual. Clinicians should be aware of the diverse triggers of SSLR and the importance of prompt identification and management to enhance patient safety. It is possible D-mannose was not the trigger, and further research is necessary to better understand the potential therapeutic applications of D-mannose, as well as the potential risks and interactions.

Keywords: serum sickness-like reaction, d-mannose, hypersensitivity reaction, urticaria

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36029 Risperidone for the Treatment of Retentive Fecal Incontinence in Children and Adolescents: A Randomize Clinical Trial

Authors: Ghazal Zahed, Leila Tabatabaee, Amirhossein Hosseini, Somaye Fatahi

Abstract:

Functional retentive overflow incontinence (Retentive FI) is the most common cause of fecal soiling in children. Affected patients may have more problems with their parents and peer group, self-esteem issues, and more psychiatric comorbidities than the general population. Therapeutic interventions for Retentive FI and related problems and comorbid conditions are needed at the same time. Based on the clinical experiences, patients with retentive FI and comorbid psychiatric disorders, were accelerated in their treatment of fecal incontinence when they were being treated with Risperidone for their psychiatric comorbidities, therefore this study was conducted to evaluate the effect of Risperidone in the treatment of Retentive FI in children and adolescents. In this double-blind randomized clinical trial, 136 patients aged 4-18 years eligible for the study were randomly divided into two groups receiving Risperidone and placebo. About half of these patients had newly diagnosed psychiatric disorders and were drug naïve, this was considered in their division. In addition to polyethylene glycol, all the participants received family counseling and education for withholding behaviors and related behavioral interventions, and nonpharmacological interventions for psychiatric comorbidities. A significant correlation was observed between the duration of treatment with risperidone and the presence of psychiatric comorbidities (P <0.001) for diurnal fecal incontinence. Based on our findings in this study, Risperidone, used commonly for psychiatric disorders in children and adolescents, may be useful in the treatment of retentive fecal incontinence in the presence of psychiatric comorbidities, and along with other interventions.

Keywords: Retentive Fecal Incontinence, Risperidone, Treatment, Pediatric, Encopresis, Atypical Antipsychotics, Fecal Soiling

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36028 Evaluating the Radiation Dose Involved in Interventional Radiology Procedures

Authors: Kholood Baron

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Radiologic interventional studies use fluoroscopy imaging guidance to perform both diagnostic and therapeutic procedures. These could result in high radiation doses being delivered to the patients and also to the radiology team. This is due to the prolonged fluoroscopy time and the large number of images taken, even when dose-minimizing techniques and modern fluoroscopic tools are applied. Hence, these procedures are part of the everyday routine of interventional radiology doctors, assistant nurses, and radiographers. Thus, it is important to estimate the radiation exposure dose they received in order to give objective advice and reduce both patient and radiology team radiation exposure dose. The aim of this study was to find out the total radiation dose reaching the radiologist and the patient during an interventional procedure and to determine the impact of certain parameters on the patient dose. Method: The radiation dose was measured by TLD devices (thermoluminescent dosimeter; radiation dosimeter device). Physicians, patients, nurses, and radiographers wore TLDs during 12 interventional radiology procedures performed in two hospitals, Mubarak and Chest Hospital. This study highlights the need for interventional radiologists to be mindful of the radiation doses received by both patients and medical staff during interventional radiology procedures. The findings emphasize the impact of factors such as fluoroscopy duration and the number of images taken on the patient dose. By raising awareness and providing insights into optimizing techniques and protective measures, this research contributes to the overall goal of reducing radiation doses and ensuring the safety of patients and medical staff.

Keywords: dosimetry, radiation dose, interventional radiology procedures, patient radiation dose

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36027 Regulating Nanocarrier and Mononuclear Phagocyte System Interactions through Esomeprazole-Based Preconditioning Strategy

Authors: Zakia Belhadj, Bing He, Hua Zhang, Xueqing Wang, Wenbing Dai, Qiang Zhang

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Mononuclear phagocyte system (MPS) forms an abominable obstacle hampering the tumor delivery efficiency of nanoparticles. Passively targeted nanocarriers have received clinical approval over the past 20 years. However, none of the actively targeted nanocarriers have entered clinical trials. Thus it is important to endue effective targeting ability to actively targeted approaches by overcoming biological barriers to nanoparticle drug delivery. Here, it presents that an Esomeprazole-based preconditioning strategy for regulating nanocarrier-MPS interaction to substantially prolong circulation time and enhance tumor targeting of nanoparticles. In vitro, the clinically approved proton pump inhibitor Esomeprazole “ESO” was demonstrated to reduce interactions between macrophages and subsequently injected targeted vesicles by interfering with their lysosomal trafficking. Of note, in vivo studies demonstrated that ESO pretreatment greatly decreased the liver and spleen uptake of c(RGDm7)-modified vesicles, highly enhanced their tumor accumulation, thereby provided superior therapeutic efficacy of c(RGDm7)-modified vesicles co-loaded with Doxorubicin (DOX) and Gefitinib (GE). This MPS-preconditioning strategy using ESO provides deeper insights into regulating nanoparticles interaction with the phagocytic system and enhancing their cancer cells' accessibility for anticancer therapy.

Keywords: esomeprazole (ESO), mononuclear phagocyte system (MPS), preconditioning strategy, targeted lipid vesicles

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36026 Influence of Animal Assisted Activity with Cat on Emotions of People with Intellectual Disabilities: Preliminary Study

Authors: Angelika Magiera, Weronika Penar, Czesław Klocek

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Intellectual disability (ID) affects approximately 1.55% of children and adults in the society of developed countries. Depending on the ID degree, the patient is burdened with additional disease entities. Intellectual disability does not only limits a person’s opportunities to participate in social life but also affects whole families. People with ID belong to the group of risk of mental illnesses, they are less emotionally stable, while families are predisposed to depression. The study was held in a day care center for people with intellectual disabilities (of various degrees of disability) on 26 people. Nurses and carers also took part. The age range of study groups ranged from 22 to 67 years. Therapeutic classes were held for four independent mixed groups (sex and intellectual disability degree) from 6 to 7 people each, lasting no more than 30 minutes. They were created by the facility's staff to make sure that a group is stable. The animal assisted activity took place with a 2.5-year-old Ragdoll cat. The animal has passed the exam (certificate entitling her to take part in felinotherapy) and had 1.5 years of work experience. Due to the different degrees of ID, an individual emotional state survey was conducted among the caregivers of those who were involved in the activity, to assess the impact of animal assisted activity with a cat on patients. A positive effect on the emotional state of people with different types of intellectual disability was observed. Caregivers and nurses of those participating in the study express willingness to continue these types of classes and consider them necessary for this group of people.

Keywords: intellectual disabilities, animal-assisted activity, cat, feline, emotions

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36025 Ethnobotanical Study, Phytochemical Screening and Biological Activity of Culinary Spices Commonly Used in Ommdurman, Sudan

Authors: Randa M. T. Mohamed

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Spices have long been used as traditional ingredients in the kitchen for seasoning, coloring, aromatic and food preservative properties. Besides, spices are equally used for therapeutic purposes. The objective of this study was to survey and document the medicinal properties of spices commonly used in the Sudanese kitchen for different food preparations. Also, extracts from reported spices were screened for the presence of secondary metabolites as well as their antioxidant and beta-lactamase inhibitory properties. This study was conducted in the Rekabbya Quartier in Omdurman, Khartoum State, Sudan. Information was collected by carrying out semi-structured interviews. All informants (30) in the present study were women. Spices were purchased from Attareen shop in Omdurman. Essential oils from spices were extracted by hydrodistillation and ethanolic extracts by maceration. Phytochemical screening was performed by thin layer chromatography (TLC). The antioxidant capacity of essential oils and ethanolic extracts was investigated through TLC bioautography. Beta lactamase inhibitory activity was performed by the acidimetric test. Ethnobotany study showed that a total of 16 spices were found to treat 36 ailments belonging to 10 categories. The most frequently claimed medicinal uses were for the digestive system diseases treated by 14 spices and respiratory system diseases treated by 8 spices. Gynaecological problems were treated by 4 spices. Dermatological diseases were cured by 5 spices while infections caused by tapeworms and other microbes causing dysentery were treated by 3 spices. 4 spices were used to treat bad breath, bleeding gum and toothache. Headache, eyes infection, cardiac stimulation and epilepsy were treated by one spice each. Other health problem like fatigue and loss of appetite and low breast milk production were treated by 1, 3 and 2 spices respectively. The majority (69%, 11/16) of spices were exported from different countries like India, China, Indonesia, Ethiopia, Egypt and Nigeria while 31% (5/16) was cultivated in Sudan. Essential oils of all spices were rich in terpenes while ethanolic extracts contained variable classes of secondary metabolites. Both essential oils and ethanolic extracts of all spices exerted considerable antioxidant activity. Only one extract, Syzygium aromaticum, possessed beta lactamase inhibitory activity. In conclusion, this study could contribute in conserving information on traditional medicinal uses of spices in Sudan. Also, the results demonstrated the potential of some of these spices to exert beneficial antimicrobial and antioxidant effect. Detailed phytochemical and biological assays of these spices are recommended.

Keywords: spices, ethnobotany, phytoconstituents, antioxidant, beta lactamase inhibition

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36024 The Effectiveness of Treating Anxiety with Reiki

Authors: Erika Humphreys

Abstract:

The effectiveness of treating anxiety with Reiki is explored within ten quantitative studies. The methodology utilized for a critical appraisal and systematic review of the literature is explained with inclusion and exclusion criteria. The theoretical framework for the project is grounded in the work of Hildegard Peplau, whose nursing theory based on the therapeutic use of self is foundational for Reiki implementation. A thorough critique of the literature is conducted for key components of robustness and believability. This critique is conducted using a structured guide addressing synthesized strengths and weaknesses of the body of literature. A synthesis of the literature explores the findings of the studies. This synthesis reports on Reiki’s effectiveness in treating anxiety within a variety of patient settings and populations, its effect on subscales of anxiety, physiological manifestations of anxiety, and pain associated with anxiety. Cultural considerations affecting Reiki’s potential effectiveness are discussed. Gaps in the literature are examined, including the studies’ narrow sample population, lack of participant exclusionary factors for controlled outcome data, and the lack of studies across time. Implications for future research are discussed with recommendations for expanded research that includes a broader variety of settings, age groups, and patient diagnoses, including anxiety disorders, for research data that is transferable. Implications for further practice for the advanced practice registered nurse (APRN) are explored, with the potential benefits for both providers and patients, including improved patient satisfaction and expansion of provider treatment modalities.

Keywords: Reiki, anxiety, complementary alternative medicine, pandemic

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36023 Association of Genetically Proxied Cholesterol-Lowering Drug Targets and Head and Neck Cancer Survival: A Mendelian Randomization Analysis

Authors: Danni Cheng

Abstract:

Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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36022 Case Report on ‘Primary Adenocarcinoma of Aberrant HER2+ Anogenital Mammary-like Glands in a Male'

Authors: Shivani Kuttuva, James Sampson, Timothy Simmons, Vinayak Thattaruparambil, Holly Burton, Peter Coyne

Abstract:

Anogenital mammary-like glands were established to be embryological remnants of breast tissue due to failed resolution of the ectodermal mammary ridge. However, recent studies are now considering this to represent normal constituents of the anogenital area with histological resemblance to the orthotopic breast tissue with multiple benign and malignant lesions arising from it. The incidence of the above has been predominant in females in the vulval region. Due to the paucity of cases reported in men, this poses a diagnostic and therapeutic challenge resulting in a delay in treatment and, thereby, poor outcomes. Our patient presented to the dermatology clinic with an itchy, purplish lesion in the peri-anal region which, on punch biopsy, was diagnosed to be Extra-mammary Paget’s disease and taken up for Wide local excision. Immunochemically, staining was positive for HER2, ER and Cytokeratin 7, keeping with the presence of actual breast tissue with no primary breast carcinoma. Due to the invasive nature of the disease, he required Abdominoperineal resection with flap reconstruction. Despite complete surgical clearance and adjuvant radiotherapy, the disease progressed to adjacent inguinal and obturator lymph nodes with origin resembling anogenital type mammary glands but histology negative for hormonal receptors of the breast.

Keywords: anogenital mammary-like glands, abdominoperineal resection, ectopic breast tissue, ectopic male breast carcinoma, peri-anal skin lesion

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36021 Rational Memory Therapy: The Counselling Technique to Control Psychological and Psychosomatic Illnesses

Authors: Sachin Deshmukh

Abstract:

Mind and body synchronization occurs through memory and sensation production. Sensations are the guiding language of subconscious mind for conscious mind to take a proper action. Mind-mechanism is based upon memories collected so far since intrauterine life. There are three universal triggers for memory creation; they are persons, situations and objects. Memory is created as sensations experienced by special senses. Based upon experiencing comfort or discomfort, the triggers are categorized as safe or unsafe triggers. A memory comprises of ‘safe or unsafe feeling for triggers, and actions taken for that feeling’. Memories for triggers are created slowly, thoughtfully and consciously by the conscious mind, and archived in the subconscious mind for future references. Later on, similar triggers can come in contact with the individual. Subconscious mind uses these stored feelings to decide whether these triggers are safe or unsafe. It produces comfort or discomfort sensations as emotions accordingly and reacts in the same way as has been recorded in memory. Speed of sensing and processing the triggers, and reacting by subconscious mind is that of the speed of bioelectricity. Hence, formula for human emotions has been designed in this paper as follows: Emotion (Stress or Peace) = Trigger (Person or Situation or object) x Mass of feelings (stressful or peaceful) associated with the Trigger x Speed of Light². We also establish modern medical scientific facts about relationship between reflex activity and memory. This research further develops the ‘Rational Memory Therapy’ focusing on therapeutic feelings conversion techniques, for stress prevention and management.

Keywords: memory, sensations, feelings, emotions, rational memory therapy

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36020 Preparation of Pegylated Interferon Alpha-2b with High Antiviral Activity Using Linear 20 KDa Polyethylene Glycol Derivative

Authors: Ehab El-Dabaa, Omnia Ali, Mohamed Abd El-Hady, Ahmed Osman

Abstract:

Recombinant human interferon alpha 2 (rhIFN-α2) is FDA approved for treatment of some viral and malignant diseases. Approved pegylated rhIFN-α2 drugs have highly improved pharmacokinetics, pharmacodynamics and therapeutic efficiency compared to native protein. In this work, we studied the pegylation of purified properly refolded rhIFN-α2b using linear 20kDa PEG-NHS (polyethylene glycol- N-hydroxysuccinimidyl ester) to prepare pegylated rhIFN-α2b with high stability and activity. The effect of different parameters like rhIFN-α2b final concentration, pH, rhIFN-α2b/PEG molar ratios and reaction time on the efficiency of pegylation (high percentage of monopegylated rhIFN-α2b) have been studied in small scale (100µl) pegylation reaction trials. Study of the percentages of different components of these reactions (mono, di, polypegylated rhIFN-α2b and unpegylated rhIFN-α2b) indicated that 2h is optimum time to complete the reaction. The pegylation efficiency increased at pH 8 (57.9%) by reducing the protein concentration to 1mg/ml and reducing the rhIFN-α2b/PEG ratio to 1:2. Using larger scale pegylation reaction (65% pegylation efficiency), ion exchange chromatography method has been optimized to prepare and purify the monopegylated rhIFN-α2b with high purity (96%). The prepared monopegylated rhIFN-α2b had apparent Mwt of approximately 65 kDa and high in vitro antiviral activity (2.1x10⁷ ± 0.8 x10⁷ IU/mg). Although it retained approximately 8.4 % of the antiviral activity of the unpegylated rhIFN-α2b, its activity is high compared to other pegylated rhIFN-α2 developed by using similar approach or higher molecular weight branched PEG.

Keywords: antiviral activity, rhIFN-α2b, pegylation, pegylation efficiency

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36019 Investigation of an Approach in Drug Delivery: Orally Fast Disintegrating Tablets

Authors: Tansel Comoglu

Abstract:

Orally fast disintegrating tablets (FDTs or ODTs) have become popular during the last decade, and manufacturing of ODTs is getting a rapidly growing area in the pharmaceutical industry. The concept of ODTs has emerged from the desire to provide patients with more conventional means of taking their medication. Drugs, that have satisfactory absorption from the oral mucosa or aimed for immediate therapeutic activity can be formulated in ODTs. After placing the ODT into the mouth, these tablets dissolve or disintegrate in the mouth usullay less than a minute, in the absence of additional water. Even though the ODT technology has taken an important path, as proved by a large group of commercial products on the drug market, there are so many problems to be solved in ODT formulations such as; formulation of hydrophobic drugs is stil a challenge, especially when the amount of drug is high. As these tablets dissolve or disintegrate in the mouth without the need of additional water, taste masking of active ingredients becomes essential in these systems because the drug is entirely released in the mouth. In ODT technology, coping with the taste of drugs is still a challenge. Resins or sweeteners or other techniques are also used in the formulation to aid taste-masking of the API. Another important factor to consider is whether they can be manufactured using conventional equipment and processes, as this will have a positive influence on manufacturing costs. Some products, however, may require a more costly, special unitdose packaging if the dosage form is fragile. In this overview, benefits, various formulation technologies, clinical studies and some future research trends of ODTs will be discussed.

Keywords: orally fast disintegrating tablets, benefits, formulation technologies, future research trends

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36018 Multilevel of Factors Affected Optimal Adherence to Antiretroviral Therapy and Viral Suppression amongst HIV-Infected Prisoners in South Ethiopia: A Prospective Cohort Study

Authors: Terefe Fuge, George Tsourtos , Emma Miller

Abstract:

Objectives: Maintaining optimal adherence and viral suppression in people living with HIV (PLWHA) is essential to ensure both preventative and therapeutic benefits of antiretroviral therapy (ART). Prisoners bear a particularly high burden of HIV infection and are highly likely to transmit to others during and after incarceration. However, the level of adherence and viral suppression, as well as its associated factors in incarcerated populations in low-income countries is unknown. This study aimed to determine the prevalence of non-adherence and viral failure, and contributing factors to this amongst prisoners in South Ethiopia. Methods: A prospective cohort study was conducted between June 1, 2019 and July 31, 2020 to compare the level of adherence and viral suppression between incarcerated and non-incarcerated PLWHA. The study involved 74 inmates living with HIV (ILWHA) and 296 non-incarcerated PLWHA. Background information including sociodemographic, socioeconomic, psychosocial, behavioural, and incarceration-related characteristics was collected using a structured questionnaire. Adherence was determined based on participants’ self-report and pharmacy refill records, and plasma viral load measurements which were undertaken within the study period were prospectively extracted to determine viral suppression. Various univariate and multivariate regression models were used to analyse data. Results: Self-reported dose adherence was approximately similar between ILWHA and non-incarcerated PLWHA (81% and 83% respectively), but ILWHA had a significantly higher medication possession ratio (MPR) (89% vs 75%). The prevalence of viral failure (VF) was slightly higher (6%) in ILWHA compared to non-incarcerated PLWHA (4.4%). The overall dose non-adherence (NA) was significantly associated with missing ART appointments, level of satisfaction with ART services, patient’s ability to comply with a specified medication schedule and types of methods used to monitor the schedule. In ILWHA specifically, accessing ART services from a hospital compared to a health centre, an inability to always attend clinic appointments, experience of depression and a lack of social support predicted NA. VF was significantly higher in males, people of age 31-35 years and in those who experienced social stigma, regardless of their incarceration status. Conclusions: This study revealed that HIV-infected prisoners in South Ethiopia were more likely to be non-adherent to doses and so to develop viral failure compared to their non-incarcerated counterparts. A multitude of factors was found to be responsible for this requiring multilevel intervention strategies focusing on the specific needs of prisoners.

Keywords: Adherence , Antiretroviral therapy, Incarceration, South Ethiopia, Viral suppression

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36017 Oil and Proteins of Sardine (Sardina Pilchardus) Compared with Casein or Mixture of Vegetable Oils Improves Dyslipidemia and Reduces Inflammation and Oxidative Stress in Hypercholesterolemic and Obese Rats

Authors: Khelladi Hadj Mostefa, Krouf Djamil, Taleb-Dida Nawel

Abstract:

Background: Obesity results from a prolonged imbalance between energy intake and energy expenditure, as depending on basal metabolic rate. Oils and proteins from sea have important therapeutic (such as obesity and hypercholesterolemia) and antioxidant effects. Sardine are a widely consumed fish in the Mediterranean region. Its consumption provides humans with various nutrients such as oils (rich in omega 3 plyunsaturated fatty acids)) and proteins. Methods: Sardine oil (SO) and sardine proteins (SP) were extracted and purified. Mixture of vegetable oils (olive-walnut-sunflower) were prepared from oils produced in Algeria. Eighteen wistar rats are fed a high fat diet enriched with 1% cholesterol for 30 days to induce obesity and hypercholesterolemia. The rats are divided into 3 groups. The first group consumes 20% sardine protein combined with 5% sardine oil (38% SFA (saturated fatty acids), 31% MIFA (monounsaturated fatty acids) and 31% PIFA (polyunsaturated fatty acids)) (SPso). The second group consumes 20% sardine protein combined with 5% of a mixture of vegetable oils (VO) containing 13% SFA, 58% MIFA and 29% PIFA (PSvo), and the third group consuming 20% casein combined with 5% of the mixture of vegetable oils and serves as a semi-synthetic reference (CASvo). Body weights and glycaemia are measured weekly After 28 days of experimentation, the rats are sacrificed, the blood and the liver removed. Serum assays of total cholesterol (TC) and triglycerides (TG) were performed by enzymatic colorimetric methods. Evaluation of lipid peroxidation was performed by assaying thiobarbituric acid reactive species (TBARS) and hydroperoxides values. The protein oxidation was performed by assaying carbonyl derivatives values. Finally, evaluation of antioxidant defense is made by measuring the activity of antioxidant enzymes, the superoxide dismutase (SOD) and the catalase (CAT).Results: After 28 days, the body weight (BW) of the rats increased significantly in SPso and SPvo groups compared to CAS group, by +11% and 7%, respectively. Cholesterolemia (TC) increased significantly in the SPso and SPvo groups compared to the CAS group (P<0.01), while triglyceridemia (TG) decreased significantly in the SPso group compared to SPvo and CAS groups (P<0.01). Albumin (marker of inflammation) increased in the PSs group compared to SPvo and CAS groups by +35% and +13%, respectively. The serum TBARS levels are -40% lower in SPso group compared to SPvo group, and they are -80% and -76% lower in SPso compared to SPvo and CAS groups, respectively. The level of carbonyls derivatives in the serum and liver are significantly reduced in the SPso group compared to the SPvo and CAS groups. Superoxide dismutase (SOD) activity decreased in liver of SPso group compared to SPvo group (P<0.01). While that of CAT is increased in liver tissue of SPso group compared to SPvo group (P<0.01). Conclusion: Sardine oil combined with sardine protein has a hypotriglyceridemic effect, reduces body weight, attenuates inflammation and seems to protect against lipid peroxidation and protein oxidation and increases antioxidant defense in hypercholesterolemic and obese rats. This could be in favor of a protective effect against obesity and cardiovascular diseases.

Keywords: rat, obesity, hypercholesterolemia, sardine protein, sardine oil, vegetable oils mixture, lipid peroxidation, protein oxidation, antioxidant defense

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36016 Narrative Review Evaluating Systematic Reviews Assessing the Effect of Probiotic Interventions on Depressive Symptoms

Authors: Ibrahim Nadeem, Mohammed Rahman, Yasser Ad-Dab’Bagh, Mahmood Akhtar

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Depression is one of the most prevalent mental illnesses and is often associated with various other medical disorders. In this review, we aim to evaluate existing systematic reviews that investigate the use of probiotics as a treatment for depressive symptoms. Five online databases were searched for relevant studies up to December 2017. Systematic reviews that included randomized controlled trials assessing the efficacy of probiotics in the treatment of depressive symptoms were included. Seven systematic reviews met the inclusion criteria. Three of these reviews conducted meta-analyses, out of which, two found probiotics to significantly improve depressive symptoms in the sample population. Two meta-analyses conducted subgroup analysis based on health status, and both found probiotics to significantly decrease depressive symptoms in patients with major depressive disorder, but only one review found it to significantly decrease in healthy patients. Another subgroup analysis was conducted based on age, and found probiotics to produce significant effects on subjects under the age of 60, but close to no effect on patients over the age of 65. Out of the four reviews that conducted qualitative analysis, three reviews concluded that probiotics have the potential to be used as a treatment. Due to the differences in clinical trials, a definitive effect of probiotics on depressive symptoms cannot be concluded. Nonetheless, probiotics seem to produce a significant therapeutic effect for subjects with pre-existing depressive symptoms. Further studies are warranted for definitive conclusions.

Keywords: depression, gut-brain axis, gut microbiota, probiotic, psychobiotic

Procedia PDF Downloads 124
36015 The Influence of Gender on Itraconazole Pharmacokinetic Parameters in Healthy Adults

Authors: Milijana N. Miljkovic, Viktorija M. Dragojevic-Simic, Nemanja K. Rancic, Vesna M. Jacevic, Snezana B. Djordjevic, Momir M. Mikov, Aleksandra M. Kovacevic

Abstract:

Itraconazole (ITZ) is a weak base and extremely lipophilic compound, with water solubility as a rate-limiting step in its absorption from the gastrointestinal tract. Its absolute bioavailability, about 55%, is maximal when its oral formulation, capsules, are taken immediately after a full meal. Peak plasma concentrations (Cmax) are reached within 2 to 5 hrs after their administration. ITZ undergoes extensive hepatic metabolism by human CYP3A4 isoenzyme and more than 30 different metabolites have been identified. One of the main ones is hydroxyitraconazole (HITZ), in which plasma concentrations are almost twice higher than those of ITZ. Gender differences in drug PK (Pharmacokinetics) have already been recognized, but variations in metabolism are believed to be their major cause. The aim of the study was to investigate the influence of gender on ITZ PK parameters after administration of oral capsule formulation, following 100 mg single dosing in healthy adult volunteers under fed conditions. The single-center, open-label PK study was performed. PK analyses included PK parameters obtained after a single 100 mg dose administration of itraconazole capsules to 48 females and 66 males. Blood samples were collected at pre-dose and up to 72.0 h after administration (1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 9.0, 12.0, 24.0, 36.0 and 72.0 hrs). The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxyitraconazole, were Cmax, AUClast, and AUCtot. Plasma concentrations of ITZ and HITZ were determined using a validated liquid chromatographic method with mass spectrometric detection, while pharmacokinetic parameters were estimated using non-compartmental methods. The pharmacokinetic analyses were performed using Kinetica software version 5.0. The mean value of ITZ Cmaxmen was 74.79 ng/ml, and Cmaxwomen was 51.291 ng/ml (independent samples test; p = 0.005). Hydroxyitraconazole had a mean value of Cmaxmen 106.37 ng/ml, and the mean value Cmaxwomen was 70.05 ng/ml. Women had, on average, lower AUClast and Cmax than men. AUClastmen for ITZ was 736.02 ng/mL*h and AUClastwomen was 566.62 ng/mL*h, while AUClastmen for HITZ was 1154.80 was ng/mL*h and AUClastwomen for HITZ was 708.12 ng/mL*h (independent samples test; p = 0.033). The mean values of ITZ AUCtotmen were 884.73 ng/mL*h and AUCtotwomen was 685.10 ng/mL*h. AUCtotmen for HITZ was 1290.41 ng/mL*h, while AUCtotwomen for HIZT was 788.60 ng/mL*h (p < 0.001). The results could point out to lower oral bioavailability of ITZ in women, since values of Cmax, AUClast, and AUCtot of both ITZ and HITZ were significantly lower in women than in men, respectively. The reason may be higher expression and activity of CYP3A4 in women than in men, but there also may be differences in other PK parameters. High variability of both ITZ and HITZ concentrations in both genders confirmed that ITZ is a highly variable drug. Further examinations of its PK are needed to justify strategies for therapeutic drug monitoring in patients treated by this antifungal agent.

Keywords: itraconazole, gender, hydroxyitraconazole, pharmacokinetics

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36014 An Audit on the Role of Sentinel Node Biopsy in High-Risk Ductal Carcinoma in Situ and Intracystic Papillary Carcinoma

Authors: M. Sulieman, H. Arabiyat, H. Ali, K. Potiszil, I. Abbas, R. English, P. King, I. Brown, P. Drew

Abstract:

Introduction: The incidence of breast ductal Carcinoma in Situ (DCIS) has been increasing; it currently represents up 20-25% of all breast carcinomas. Some aspects of DCIS management are still controversial, mainly due to the heterogeneity of its clinical presentation and of its biological and pathological characteristics. In DCIS, histological diagnosis obtained preoperatively, carries the risk of sampling error if the presence of invasive cancer is subsequently diagnosed. The mammographic extent over than 4–5 cm and the presence of architectural distortion, focal asymmetric density or mass on mammography are proven important risk factors of preoperative histological under staging. Intracystic papillary cancer (IPC) is a rare form of breast carcinoma. Despite being previously compared to DCIS it has been shown to present histologically with invasion of the basement membrane and even metastasis. SLNB – Carries the risk of associated comorbidity that should be considered when planning surgery for DCIS and IPC. Objectives: The aim of this Audit was to better define a ‘high risk’ group of patients with pre-op diagnosis of non-invasive cancer undergoing breast conserving surgery, who would benefit from sentinel node biopsy. Method: Retrospective data collection of all patients with ductal carcinoma in situ over 5 years. 636 patients identified, and after exclusion criteria applied: 394 patients were included. High risk defined as: Extensive micro-calcification >40mm OR any mass forming DCIS. IPC: Winpath search from for the term ‘papillary carcinoma’ in any breast specimen for 5 years duration;.29 patients were included in this group. Results: DCIS: 188 deemed high risk due to >40mm calcification or a mass forming (radiological or palpable) 61% of those had a mastectomy and 32% BCS. Overall, in that high-risk group - the number with invasive disease was 38%. Of those high-risk DCIS pts 85% had a SLN - 80% at the time of surgery and 5% at a second operation. For the BCS patients - 42% had SLN at time of surgery and 13% (8 patients) at a second operation. 15 (7.9%) pts in the high-risk group had a positive SLNB, 11 having a mastectomy and 4 having BCS. IPC: The provisional diagnosis of encysted papillary carcinoma is upgraded to an invasive carcinoma on final histology in around a third of cases. This has may have implications when deciding whether to offer sentinel node removal at the time of therapeutic surgery. Conclusions: We have defined a ‘high risk’ group of pts with pre-op diagnosis of non-invasive cancer undergoing BCS, who would benefit from SLNB at the time of the surgery. In patients with high-risk features; the risk of invasive disease is up to 40% but the risk of nodal involvement is approximately 8%. The risk of morbidity from SLN is up to about 5% especially the risk of lymphedema.

Keywords: breast ductal carcinoma in Situ (DCIS), intracystic papillary carcinoma (IPC), sentinel node biopsy (SLNB), high-risk, non-invasive, cancer disease

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36013 Improving the Growth, Biochemical Parameters and Content and Composition of Essential Oil of Mentha piperita L. through Soil-Applied N, P, and K

Authors: Bilal Bhat, M. Masroor A. Khan, Moin Uddin, M. Naeem

Abstract:

Aromatic herb, peppermint (Mentha piperita L.), is a natural hybrid (M. aquatica × M. spicata) with immense therapeutic uses, apart from other potential uses. Peppermint oil is one of the most popular and widely used essential oil (EO), because of its main components menthol and menthone. In view of enhancing growth, yield and quality of this medicinally important herb, a pot experiment was conducted in the net-house of the department. The experiment was aimed at studying the effect of graded levels of N, P, and K on growth, biochemical characteristics, and content and composition of EO in Mentha piperita L. Six NPK treatments (viz. N0P0K0, N20P20K20, N40P40K40, N20+20 P20+20 K20+20, N60P60K60, and N30+30 P30+30 K30+30) were tested. The plants were harvested 150 days after transplanting. The crop performance was assessed in terms of growth attributes, physiological activities, herbage yield and content as well as yield of active constituents of Mentha piperita L. Biochemical parameters were analyzed spectrophotometrically. The EO was extracted using Clevenger’s apparatus and the active constituents of the oil were determined using Gas Chromatography. Split-dose application of N, P and K (N30+30 P30+30 K30+30) ameliorated most of the parameters significantly including, fresh and dry weight of plant, NPK content, chlorophyll and carotenoids content, and the activities of carbonic anhydrase and nitrate reductase in the leaves. It also enhanced the EO content (44.0%), EO yield (91.0%), menthol content (14.1%), menthone content (34.0%), menthyl acetate content (16.9%) and 1, 8-cineole content (43.7%) but decreased the pulegone content (36.8%). Conclusively, the fertilization proved useful in enhancing the EO content, yield and other EO components of the plant. Thus, the yield and quality of EO of peppermint may be improved by this agricultural strategy.

Keywords: mentha piperita, menthol, menthone, EO

Procedia PDF Downloads 480