Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Παρασκευή 1 Ιανουαρίου 2021

Biomedical and Biotechnology Research

Understanding the genetics of gastric and esophageal cancer using Drosophila melanogaster as a model organism
Preeti Thiyagarajan, Venkatachalam Deepa Parvathi

Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):269-273

Drosophila melanogaster, a vicious model, has helped in significant discoveries about several conserved mechanisms. The insect intestine had remained unexplored until the identification of adult somatic stem cells which triggered the invention of genetic amenability of this insect organ in powerful and artistic ways. A variety of mechanisms within the fruit flies' intestine are conserved in human gastrointestinal systems and will, therefore, become relevant within the context of human pathologies such as gastrointestinal cancers and obesity. In line with current guidelines, maintaining a high degree of suspicion of hereditary etiology (genetic involvement) helps in disease diagnosis. In this review, genetics of two crucial cancers are discussed. Mutation or transcriptional silencing of the cadherin-1 (CDH1) gene and tumor protein p53 gene is related to familial diffuse gastric cancer (GC) and esophageal adenocarcinoma, respectively. Testing for CDH1 mutations in patients with familial clustering of hereditary diffuse GC has proven consistent. Further studies on the expression and also the alteration within the proteins within the E-CDH pathways and Hippo pathway may function as biomarkers for early detection. Dysregulation of various mechanisms ends up in invasion, proliferation, and metastases. The promise of targeted therapy and personalized medicine in improving the clinical outcome is now closer than it has ever been.


General awareness on hantavirus infection: A brief review
Rashed Noor

Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):274-279

Hantavirus is a negative, stranded RNA virus, largely known to be transmitted to humans, especially working in forestry from the rodents. The human-to-human transmission of this virus is still in obscure; however, upon transmission of this virus from the rodent fluids, its fatality is noticed mainly through the hyperinflammatory syndrome and the cardiopulmonary syndrome. Several reports revealed an alternation of the immune response including the natural killer cells, CD8+ T cells, neutrophils, and several cytokines during the viral pathogenesis. Unlike the other emerging viruses including the currently ongoing novel coronavirus (COVID-19) pandemic, the global mortality rate due to hantavirus infection is so far very low, which, in turn, made the general people all around the world know a very little about this virus. Besides, no effective antiviral therapy including vaccines has yet been developed to combat the viral infection. Lots of comprehensive reports elaborately discussed this virus pointing toward its dreadfulness. The current review discussed the fatal effects of the hantavirus infection in a relatively simplistic way, which can be easily understood by the general community who are still unaware of the risks posed by this relatively uncommon virus.


Genetic makeup and associated virulence posed by the enteropathogenic Escherichia coli and the Enterotoxigenic Escherichia coli pathotypes
Syeda Muntaka Maniha, Rashed Noor

Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):280-284

The enteropathogenic Escherichia coli (EPEC) is known to trigger diarrhea in infants, whereas the enterotoxigenic E. coli (ETEC) accounts for the children's diarrhea and the travelers' diarrhea. Transmission of the pathogenic bacteria usually occurs in a fecal–oral route usually originating from the poultry items. Thus, the study relating these E. coli pathotypes to the required virulence factors would be of great interest for the welfare of mass public health. Although the reports on the food-oriented pathogenic E. coli so far are actually uncountable, the present review especially concentrated on the genetics of virulence factors required for the pathogenesis by EPEC and ETEC based on the information given by the previous literature. The review focused on the expressional regulation of the components required for the EPEC pathophysiological impact on humans. The necessary studies correlating the genome with the expression of the virulence factors have been well discussed.


Does epstein–barr virus participate in the development of breast cancer? A brief and critical review with molecular evidences
Muhammad Usman, Yasir Hameed, Mukhtiar Ahmad

Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):285-292

The oncogenic potential of Epstein–Barr virus (EBV) has been well studied in human breast cancer (BC) so far but still controversies surround its role. In the present study, we aimed to perform a comprehensive and critical review of the results and methodologies used by the previous studies to identify the association between EBV markers with human breast. We also proposed a criterion based on the Bradford hill postulates of causation and EBV prevalence to evaluate the results of previous studies for proving EBV etiological role in breast cancer. A PubMed search engine-based strategy was implemented to retrieve all the relevant studies. In total, 50 original studies were retrieved. Out of which 20 were case–control studies while others were not. The positivity ratios of EBV detection in breast cancer samples varied study wise. Few studies did not identify the EBV markers in breast cancer while others identified it with different detection positivity ratios varying from 2.9% to 75.8%. Similarly, the EBV detection positivity ratios in normal and benign samples also varied between 0%–35% and 0%–75.8%, respectively. In total, 18 out of 20 case–control studies, the positivity ratios of EBV detection were higher or equal in breast samples as compared to controls, while two case–control studies also report the opposite results. However, the odds ratios and confidence intervals were not reported. The results failed to prove EBV as a potential biomarker of breast cancer but rather suggested its role as a cause-effect or at least co-participant.


The role of estrogen in breast cancer
Roaa Khadem, Fatimah Chassab Mahdi, Karrar AI-Mosawi, Ali Abdul Hussein S. AL-Janabi

Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):293-296

Estrogen has a significant effect on the development of breast cancer. Its activities in the human body are mainly performed by binding to cellular estrogen receptor (ER). Breast cancer in relate to the presence of ER can be divided into ER-positive and ER-negative breast cancer. The role of estrogen and its receptors in the development of breast cancer will be discussed in this review.


Influence of De novo mutation in autism
Ann Mary Alappat Sanjeev, Bharathi Kathirvel, Kaviya Mohandass, Vijaya Anand Arumugam

Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):297-301

Autism and autism spectrum disorders (ASD) affects the areas of social awareness and interaction, verbal and nonverbal communication, and behaviors and interests, which are grouped among neurobehavioral disorders. One in 68 children is affected with ASD according to the estimate from the Center for Disease Control and Prevention's autism and developmental disabilities monitoring network and an increasing prevalence observed worldwide. A characteristic heterogeneity in ASD determined genetic variability as a major contributor. Whole-exome sequencing of ASD individuals revealed that discrete de novo mutation (single-nucleotide variation or small indels) also contribute to the overall genetic risk of ASD apart from rare genetic variation affecting single nucleotides of protein-coding DNA or rare genomic copy number variants as assessed through other high-throughput genomic methods. These genes are involved in synaptic transmission and regulated during brain development by acting upstream or downstream of Wingless- related integration site (WNT), bone morphogenetic proteins/transforming growth factor-β, sonic hedgehog, fibroblast growth factor, and retinoic acid signaling pathways. The current review focuses on genes involved in synaptic function, undergoing de novo mutation leading to ASD condition.


FNCas9 editor-linked uniform detection assay: An innovative COVID-19 sleuth
Tarun Kumar Suvvari, MD Nawaz, Mani Kruthika Mantha

Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):302-304

Relying on traditional diagnostic approaches like quantitative polymerase chain reaction is not appropriate for both time and cost in sudden outbreaks and pandemics such as COVID-19. In such cases, diagnostic approaches through rapid sequencing of pathogenic DNA and RNA are important for accelerated clinical prognosis. FNCas9 Editor-Linked Uniform Detection Assay (FELUDA) is one such diagnostic approach toward the pathogenic genome, developed by CSIR-IGIB. FELUDA is a paper strip diagnostic test like pregnancy, based on clustered regularly interspaced short palindromic repeats/Cas technology of gene editing. FELUDA showed 96% sensitivity and 98% specificity across all range of viral loads in clinical samples. Due to its low cost, it can drastically reduce the Indian budget toward the rapid testing and COVID-19 diagnostic kits.


Phytochemical and antioxidant assessments of Dioscorea bulbifera stem tuber
Othuke Bensandy Odeghe, Elias Adikwu, Chioma Cynthia Ojiego

Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):305-311

Background: Dioscorea bulbifera (D. bulbifera) is used in traditional medicine for the treatment of many disease conditions. However, there is a paucity of information on the antioxidant potential of its stem tuber. Methods: The antioxidant activity of the methanolic extract of D. bulbifera stem tuber was evaluated by measuring its ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide anion radical (O2-) and nitric oxide (NO) radical. It was also analyzed for bioactive secondary metabolites using standard qualitative and quantitative spectrophotometric methods. Results: The extract showed total phenolic content (0.243 ± 0.052 mg) gallic acid equivalent compared to tannins content (0.259 ± 0.034 mg). Low flavonoid contents (0.060 ± 0.025 mg) quercetin equivalent (QE) and high flavonol contents (1.399 ± 0.075 mg) QE were found in the extract. The extract showed a potent concentration-dependent DPPH radical inhibitory potential with maximal inhibition activity (69.39 ± 1.62%) at 5000 μg/mL compared to ascorbic acid with maximal inhibition activity (88.9 ± 2.67%) at the same concentration. The extract produced maximal O2- anion inhibitory activity (52.86 ± 0.68%) at 2500 μg/mL compared to quercetin with maximal inhibitory activity (68.23 ± 0.41%) at the same concentration. The extract exhibited NO activity in a dose-depend fashion when compared to α-tocopherol. Conclusion: These results showed that D. bulbifera stem tuber extract contains bioactive secondary metabolites with potent-free radical scavenging activity, which could be extracted and standardized for use as food, medicine, and in industries.


Detailed analyses about predictive value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in invasive lobular breast cancer
Esra Arslan, Tamer Aksoy

Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):312-317

Backgrounds: Management of invasive lobular breast cancer (ILC) is limited with only using standard uptake value (SUV) max of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography. We aimed detailed predictive, prognostic and clinical value of parameters, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) with survival data. Methods: Forty-nine ILC was included in this study. SUVmax, MTV, and TLG documented in molecular and histopathological subtypes. SUVmax, MTV, and TLG compared with nodal involvement, distant metastasis, estrogen receptor (ER), progesterone receptors (PR) and HER status, Ki-67 and survival data. Results: 61.2% luminal A, 36.7% luminal B and 2.0% TN. 53.1% classic and 46.9% pleomorphic. 93.9% ER + and 81.6% had e-cadherin loss. Mean SUVmax was 8.32 ± 4.73. No statistically significant relationship found between classical and pleomorphic with SUVmax (P = 0.616). FDG uptake found significantly higher with tumor >2 cm (P = 0.039). Luminal B SUVmax significantly higher than luminal A (P = 0.013). PR-, Ki-67 high expression, axillary involvement and luminal B significantly reduced survival time (P = 0.034, 0.019, 0.032, and 0.005, respectively). Statistically significant correlation found between high MTV and TLG, tumor diameter (TD) (P = 0.001 and 0.000, respectively). Conclusions: Loss e-cadherin and pleomorphic types did not affect the prognosis. ILC shows low FDG sensitivity compared other breast cancer types, it found to be significantly associated with prognostic factors; TD, molecular subtype, Ki-67 and metastasis. Although volumetric parameters did not add extrapredictive value to FDG involvement pattern, it was found that method remains in diagnosis, staging, and treatment follow-up of ILC.


Synthesis, characterization, and In vitro antibacterial activity and molecular docking studies of N4, N4'-dibutyl-3,3'-dinitro-[1,1'-Biphenyl]-4,4'-diamine
K Muddukrishnaiah, V Vijayakumar, B Samuel Thavamani, VP Shilpa, N Radhakrishnan, Heba S Abbas

Biomedical and Biotechnology Research Journal (BBRJ) 2020 4(4):318-322

Background: Resistant growth is recognized as a significant public health hazard to human health worldwide among the most critical bacterial diseases. The evolving multidrug-resistant species are now commonly found in community settings, not just in the hospital area, which means that antibiotic bacteria reservoirs are beyond the hospital. Aim: In this study, we synthesized novel N4, N4'-dibutyl-3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine from 3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine and evaluation of its antimicrobial activity against clinical bacteria. Methods: Single-step synthesis of novel N4, N4'-dibutyl-3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine from 3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine and well characterized using spectroscopic methods, namely FT-IR, NMR, mass spectrometry, and CHNS. Besides, prepared compound molecular docking investigations, molecular physicochemical, absorption, distribution, metabolism, and excretion (ADME) analysis were also carried out. Results and Discussion: Novel Synthesized N4, N4'-dibutyl-3,3'-diaminobenzidine (DAB) was conducted for antibacterial activity against clinical Klebsiella spp. and Staphylococcus aureus and Pseudomonas spp. by the disc-diffusion method and followed by serial dilution method. N4, N4'-dibutyl-3,3'-DAB showed bacteriostatic action of 500 μg/ml, 1000 μg/ml for Klebsiella spp. and Staphylococcus aureus. The molecular physicochemical investigation exhibited that 1 violation and ADME analysis presented a low gastro intestinal effect. Docking investigations disclosed the capability of synthesized molecule potential to dock with beta-lactamase protein through patch dock methodology. Conclusion: N4, N4'-dibutyl-3,3'-DAB is the novel compound that was found to be attractive for the “drug hunters” as a potential agent for the management of infectious diseases against the human pathogens Klebsiella spp. and Staphylococcus aureus.



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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Telephone consultation 11855 int 1193,

Pharmaceutical Sciences

Preparation and characterization of ethylcellulose microspheres for sustained-release of pregabalin
Haya Yasin, Bashar Al-Taani, Mutaz Sheikh Salem

Research in Pharmaceutical Sciences 2021 16(1):1-15

Background and purpose: Pregabalin is used in the treatment of epilepsy, chronic pain, and other psychological disorders. Preparation of pregabalin in the sustained-release formulation will enhance patient compliance and reduce the incidence of side effects. The aim of this study was to prepare sustained-release microspheres for pregabalin utilizing ethylcellulose and evaluate the processing factors that influence the fabrication and the performance of the prepared microspheres. Experimental approach: The microspheres were prepared using the water-oil-oil double emulsion solvent evaporation method. Microspheres were characterized for particle size, encapsulation efficiency, and in vitro drug release. The influence of the processing variables on the characteristics of the prepared microspheres was studied. Microspheres solid-state characterization performed using differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy. Findings/Results: The results described in the context of the current work illustrated the suitability of the water-oil-oil system in the preparation of sustained-release microspheres for pregabalin. The optimum formulation was prepared at a drug to polymer ratio of 1:3 w/w, stirring speed of 600 rpm, surfactant concentration of 1.5%, and external phase volume of 150 mL. This formula produced microspheres particle size in the range 600-1000 μm, with 87.6% yield, and 80.14 ± 0.53% encapsulation efficiency. Drug release from the microspheres was found to be diffusion controlled, with a pH-independent behavior. Conclusion and implication The current work presented a successful attempt to fabricate a sustained-release microsphere comprising pregabalin. This will help overcome the frequent dosing problems with conventional pregabalin dosage forms and improve product performance.


Immunomodulatory effects of standardized extract of Curcuma mangga val. on cytokines, antibody and delayed-type hypersensitivity response in Wistar rats
Yuandani , Sony Eka Nugraha, Lia Laila, Denny Satria

Research in Pharmaceutical Sciences 2021 16(1):16-25

Background and purpose: Recently, we have highlighted the immunomodulatory activity of Curcuma mangga Val. on phagocytosis ability. The current study was conducted to determine the immunomodulatory effects of the standardized extract of C. mangga rhizomes by in vitro and in vivo studies. Experimental approach: The C. mangga extract was standardized according to a guideline for herbal preparation. The extract was investigated for its immunomodulatory effects on gene expression of cytokines, cytokines and antibody production as well as delayed-type hypersensitivity (DTH) response. The gene expression of cytokines on lipopolysaccharide-induced-RAW 264.7 cells was analysed by reverse transcription-polymerase chain reaction (RT-PCR) method. The effect of the extract on DTH response was investigated by the paw edema method, meanwhile the effects of the extract on antibody and cytokine production from normal and cyclophosphamide-induced Salmonella typhimurium infected rats were determined using an enzyme-linked immunosorbent assay (ELISA). Findings/Results: The extract of C. mangga demonstrated an inhibitory effect on gene expression of interleukin-1β (IL-1β), tumor necrosis factor-α, and IL-6 as compared to lipopolysaccharide-induced cells. The extract also depicted inhibitory activity on IL-4 production as compared to the negative control. Whereas, the DTH response and production of immunoglobulin G from both groups after treatment with C. mangga extract were higher than those of negative control (P < 0.05). Conclusion and implications: The results indicated that the C. mangga extract has immunomodulatory effects, emphasizing its potential to be developed as immunotherapeutic agent.


Prodigiosin induced the caspase-dependent apoptosis in human chronic myelogenous leukemia K562 cell
Maryam Niakani, Ahmad Majd, Parviz Pakzad, Hassan Malekinejad

Research in Pharmaceutical Sciences 2021 16(1):26-34

Background and purpose: Chronic myeloid leukemia (CML) as a myeloproliferative disease is characterized by increased cellularity of bone marrow. Implementing the latest treatment protocols is currently accompanied by serious and life-threatening side effects. There are worldwide attempts to find new effective and potent therapeutic agents with minimal side effects on CML patients. This in vitro study was carried out to discover the potential antiproliferative and apoptotic effects of naturally produced prodigiosin (PDG) on K562 cells as an accepted model of CML. Experimental approach: The anti-proliferative effect of PDG was measured by MTT assay. To highlight the mechanism of cytotoxicity, the apoptotic cell death pathway was investigated by morphological and biochemical assessments. The dual acridine orange/ethidium bromide staining technique and western blotting method were applied to assess the mechanism of the potential apoptotic impact of PDG on K562 cells. Findings/Results: PDG-induced time- and concentration-dependent anti-proliferative effects were revealed with an estimated IC50 value of 54.06 μM. The highest cell viability reduction (60%) was recorded in cells, which were exposed to 100 μM concentration. Further assays demonstrated that in the dual acridine orange/ethidium bromide staining method the cell population in the late apoptosis phase was increased in a concentration-dependent manner, which was confirmed with remarkable DNA fragmentation. Conclusion and implications: We found that the PDG-induced apoptosis in K562 cells is mediated through the caspase-3 activation both in mRNA and protein levels. Our results suggest that PDG could be a potent compound for further pharmacokinetic and pharmacodynamics studies in the in vivo model of CML.


Synthesis, antioxidant activity, and density functional theory study of some novel 4-[(benzo[d]thiazol-2-ylimino)methyl]phenol derivatives: a comparative approach for the explanation of their radical scavenging activities
Mohammad hossein Asgarshamsi, Afshin Fassihi, Farshid Hassanzadeh, Lotfollah Saghaei, Ahmad Movahedian Attar, Hossein Mohammad-Beigi

Research in Pharmaceutical Sciences 2021 16(1):35-47

Background and purpose: Radicals produced by Fenton and Haber-Weiss reactions play detrimental roles in our body. Some oxidized proteins as toxic configurations are identified in amyloid-β deposits. These deposits mostly occur in conditions, such as Alzheimer’s disease. Here, we report the synthesis, evaluation of the antioxidant activity, and implementation of density functional theory (DFT) calculations of some4- [(benzo[d]thiazol-2-ylimino) methyl]phenol derivatives. The aim of this study was to provide a comparative theoretical-experimental approach to explain the antioxidant activities of the compounds. Experimental approach: Compounds were synthesized by the reaction between para hydroxybenzaldehyde and aminobenzothiazole derivatives. The scavenging activity of the compounds was evaluated. Various electronic and energetic descriptors such as high occupied molecular orbital and low unoccupied molecular orbital energy gaps, bonding dissociation enthalpy of OH bond, ionization potential, electron affinity, hardness, softness, and spin density of the radical and neutral species were calculated. DFT calculations with B3LYP hybrid functional and 6-311++ G** basis set in the polarizable continuum model were utilized to obtain these descriptors. Findings/Results: Ascorbic acid showed the best DPPH scavenging activity. However, 4d and 4c showed promising antioxidant activity. The values of EHOMO for 4c and 4d were closer to zero, thus, they showed the best scavenging activities. The computational results were in accordance with the experimental ones. The energetic descriptors indicated that the sequential proton loss-electron transfer mechanism is preferred over other mechanisms. Conclusion and implication: Antioxidant activity of 4-[(Benzo[d]thiazol-2-ylimino) methyl]phenol derivatives confirmed by experimental and theoretical documents proves them as novel antioxidants against amyloid-β based disease.


The potential neuroprotective roles of olive leaf extract in an epilepsy rat model induced by kainic acid
Safoura Khamse, Saeed Mohammadian Haftcheshmeh, Seyed Shahabeddin Sadr, Mehrdad Roghani, Mohammad Kamalinejad, Parvane Mohseni Moghaddam, Ravieh Golchoobian, Fatemeh Ebrahimi

Research in Pharmaceutical Sciences 2021 16(1):48-57

Background and purpose: Epilepsy is recognized as a chronic neurologic disease. Increasing evidence has addressed the antioxidant and anti-inflammatory roles of olive leaf extract (OLE) in neurodegenerative diseases. So, the current study aimed to investigate the neuroprotective roles of OLE in epilepsy. Experimental approach: Forty rats were divided into 4 groups including a control group, sham group, kainic acid (KA) group, and KA + OLE group. KA (4 μg/rat) was injected intrahippocampal, and OLE (300 mg/kg) was orally administrated for 4 weeks. Animals were sacrificed, and their hippocampi were isolated. KA- induced seizure activity was recorded. Oxidative stress index was assessed by measuring its indicators including malondialdehyde (MDA), nitrite, nitrate, and glutathione (GSH) as well as the catalase (CAT) activity. The supernatant concentration of tumor necrosis factor-α (TNF-α) and the apoptosis rate in neurons were measured. Findings/Results: Treatment with OLE significantly reduced the seizure score. OLE decreased oxidative stress index by reducing the concentration of MDA, nitrite, and nitrate as well as increasing the level of GSH. OLE had a significant anti-apoptotic effect on neurons. However, CAT activity and the level of TNF-α were not affected. Conclusion and implications: Our findings indicated neuroprotective properties of OLE, which is mainly mediated by its antioxidant and anti-apoptotic effects, therefore, could be considered as a valuable therapeutic supplement for epilepsy.


Interactions and effects of food additive dye Allura red on pepsin structure and protease activity; experimental and computational supports
Fatemeh Balaei, Mohabbat Ansari, Negin Farhadian, Sajad Moradi, Mohsen Shahlaei

Research in Pharmaceutical Sciences 2021 16(1):58-70

Background and purpose: Today, color additives such as Allura red (AR) are widely used in different kinds of food products. Pepsin is a globular protein that is secreted as a digestive protease from the main cells in the stomach. Because of the important role of pepsin in protein digestion and because of its importance in digestive diseases the study of the interactions of pepsin with chemical food additives is important. Experimental approach: In this study, the interactions between AR and pepsin were investigated by different computational and experimental approaches such as ultraviolet and fluorescence spectroscopy along with computational molecular modeling. Findings/Results: The experimental results of fluorescence indicated that AR can strongly quench the fluorescence of pepsin through a static quenching. Thermodynamic analysis of the binding phenomena suggests that van der Waals forces and hydrogen bonding played a major role in the complex formation. The results of synchronous fluorescence spectra and furrier transformed infra-red (FTIR) experiments showed that there are no significant structural changes in the protein conformation. Also, examined pepsin protease activity revealed that the activity of pepsin was increased upon ligand binding. In agreement with the experimental results, the computational results showed that hydrogen bonding and van der Waals interactions occurred between AR and binding sites. Conclusion and implications: From the pharmaceutical point of view, this interaction can help us to get a deeper understanding of the effect of this synthetic dye on food digestion.


Protective effects of a standardized extract of Iris germanica on pancreas and liver in streptozotocin-induced diabetic rats
Mohammad Reza Mahdinezhad, Sara Hooshmand, Mohammad Soukhtanloo, Shirin Taraz Jamshidi, Sajad Ehtiati, Ahmad Ghorbani

Research in Pharmaceutical Sciences 2021 16(1):71-78

Background and purpose: Previous studies have shown the antioxidant, anti-inflammatory, immunomodulatory, and hypolipidemic activities of Iris germanica. The aim of the present study was to evaluate the protective effects of hydroalcoholic extract of Iris germanica rhizomes on streptozotocin-induced diabetic rats. Experimental approach: Twenty-four male Wistar rats were randomly assigned into four groups including a normal control group, diabetic control group, diabetic groups treated for 4 weeks with 100 and 200 mg/kg/day of the Iris germanica extract (IGE). Findings/Results: Induction of diabetes significantly decreased the body weight gain and considerably increased the serum levels of glucose, triglyceride, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Diabetes also diminished the antioxidant capacity of the liver (decrease of thiol groups) and significantly degenerated pancreatic islands. The IGE at both doses of 100 and 200 mg/kg significantly reduced the levels of glucose, triglyceride, AST, ALT, and ALP. Moreover, IGE increased the total antioxidant capacity of the liver and ameliorated pancreatic island morphology. The extract had no significant effect on body weight and BUN level. Conclusion and implication: These findings suggest that Iris germanica rhizomes inhibits the progression of hyperglycemia and hypertriglyceridemia and has protective effects against diabetes-induced injury of the liver and pancreas. Therefore, this plant has the potential to be used as a natural product for controlling diabetes.


Chitosan/tripolyphosphate nanoparticles in active and passive microchannels
Mona Akbari, Zohreh Rahimi, Masoud Rahimi

Research in Pharmaceutical Sciences 2021 16(1):79-93

Background and purpose: In recent years, the interest in chitosan nanoparticles has increased due to their application, especially in drug delivery. The main aim of this work was to find a suitable method for simulating pharmaceutical nanoparticles with computational fluid dynamics (CFD) modeling and use it for understanding the process of nanoparticle formation in different types of microchannels. Experimental approach: Active and passive microchannels were compared to find the advantages and disadvantages of each system. Twenty-eight experiments were done on microchannels to quantify the effect of 4 parameters and their interactions on the size and polydispersity index (PDI) of nanoparticles. CFD was implemented by coupling reactive kinetics and the population balance method to simulate the synthesis of chitosan/tripolyphosphate nanoparticles in the microchannel. Findings/Results: The passive microchannel had the best performance for nanoparticle production. The most uniform microspheres and the narrowest standard deviation (124.3 nm, PDI = 0.112) were achieved using passive microchannel. Compared to the active microchannel, the size and PDI of the nanoparticles were 28.7% and 70.5% higher for active microchannels, and 55.43% and 105.3% higher for simple microchannels, respectively. Experimental results confirmed the validity of CFD modeling. The growth and nucleation rates were determined using the reaction equation of chitosan and tripolyphosphate. Conclusion and implications: CFD modeling by the proposed method can play an important role in the prediction of the size and PDI of chitosan/tripolyphosphate nanoparticles in the same condition and provide a new perspective for studying the production of nanoparticles by numerical methods.


Protective and therapeutic effects of ethanolic extract of Nasturtium officinale (watercress) and vitamin E against bleomycin-induced pulmonary fibrosis in rats
Sanaz Ramezani, Iraj Javadi, Esmaeel Panahi Kokhdan, Navid Omidifar, Jafar Nikbakht, Heibatollah Sadeghi, Amir Hossein Doustimotlagh, Nazanin Danaei, Reza Abbasi, Hossein Sadeghi

Research in Pharmaceutical Sciences 2021 16(1):94-102

Background and purpose: Pulmonary fibrosis is a chronic disease of the lungs caused by inflammation, species of reactive oxygen, and immune defects. Antioxidant properties of Nasturtium officinale has been reported in some studies. Therefore, the objective of the current study was to evaluate the effect of ethanolic extract of Nasturtium officinale (EENO) on bleomycin (BLM)-induced lung fibrosis in rats. Experimental approach: Forty adult male Wistar rats (180-220 g) were randomly divided into 5 experimental groups. Normal control, BLM control received a single dose of BLM (6 IU/kg) intratracheally only on the first day, EENO + BLM group received EENO (500 mg/kg) one week before intratracheal BLM instillation and two weeks afterward, BLM + EENO group and BML + vitamin E group received EENO (500 mg/kg) and vitamin E (500 mg/kg) half-hour after BLM installation, respectively. The animals were sacrificed on day 22. Change in body weight, lung index, serum level of malondialdehyde (MDA) and nitric oxide (NO) metabolite, lung tissue hydroxyproline content and lung pathology were assessed. Findings/Results: Pre- or post-treatment with EENO attenuated pulmonary fibrosis as evidenced by normalized lung index, improved histological changes and inhibited collagen deposition (hydroxyproline) in the animal lung. EENO also decreased MDA and NO metabolite release in comparison to the BLM control. vitamin E (500 mg/ kg) also significantly inhibited the BLM-induced lung toxicity. Conclusions and implications: EENO can prevent BLM-induced lung fibrosis in rats via antioxidant activities. However, more studies are needed to elicit the exact mechanism of this effect.


Development and characterization of a nano-drug delivery system containing vasaka phospholipid complex to improve bioavailability using quality by design approach
Nandhini Sundaresan, Ilango Kaliappan

Research in Pharmaceutical Sciences 2021 16(1):103-117

Background and purpose: Vasicine is a potential bronchodilator and can be used for the effective management of asthma and bronchitis. It has low absorption in the gastrointestinal tract due to its poor solubility thereby low bioavailability. The objective of this research was to develop a novel drug delivery system of vasaka extract to improve its bioavailability by enhancing the solubility and absorption of vasicine. Experimental approach: Vasaka-loaded phytosomes were developed and optimized by thin-layer hydration technique using systematic quality by design approach. Box-Behnken design (32 factorial design) using Design-Expert software was employed to optimize phytosome wherein phosphatidylcholine concentration (X1), stirring temperature (X2), and stirring time (X3) were selected as independent variables. Yield (%), particle size (nm), and entrapment efficiency (%) were evaluated as responses. The optimized phytosome was characterized by studying the surface morphology such as FE-SEM and TEM analysis, thermal characteristics by thermal gravimetric analysis and spectral and diffraction studies by FTIR and XRD analysis and studying the dissolution behaviour of phytosome by in vitro release study. Findings/Results: The percentage yield, particle size, and entrapment efficiency values of the phytosomes were found in the range of 30.03-97.03%, 231.0-701.4 nm, and 20.02-95.88% w/w, respectively. The optimized phytosome showed the zeta potential of -23.2 mV exhibited good stability and SEM and TEM analysis revealed the spherical shape and smooth particles with the uniform particle size distribution of phytosomes. The comparative in vitro drug release study of vasaka extract and phytosome revealed the sustained release characteristics of phytosome which reached 68.80% at 8 h compared to vasaka extract reached a maximum of 45.08% at 4 h. Conclusion and implication: The results highlighted the importance of optimization of formulation development using quality by design strategy to achieve consistent quality of pharmaceutical products.



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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Telephone consultation 11855 int 1193,

Πέμπτη 31 Δεκεμβρίου 2020

Psychomotor development of 4-year-old deaf children with cochlear implants: Three case studies.

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Authors: Ganc M, Kobosko J, Jedrzejczak WW, Kochański B, Skarzynski H

Abstract
OBJECTIVES: Hearing is one of our most important senses, and hearing ability has an enormous impact on a child's psychomotor development. Children with auditory perception disorders may show abnormal development in terms of speech, language, and communication skills, as well as other disorders involving the cognitive sphere, social-emotional interactions, and motor development. This paper describes different paths of psychomotor development in three 4-year-old children. All were born with bilateral profound sensorineural hearing loss and were implanted early on with a cochlear implant. A longitudinal study of the children's psychomotor development was done for 3 years from the time of cochlear implantation.
METHODS: We present three children with congenital, profound bilateral sensorineural hearing loss. Psychomotor development was evaluated using the Children Development Scale (CDS) and the Psychomotor Development Evaluation Cards (PDEC). The three children were: Girl A (4 years 2 months 17 days) - a user of one CI, last assessment of psychomotor development (PDEC) was 37 months after CI activation; Boy B (4 years 3 months 21 days) - a user of two CIs, last assessment of psychomotor development (PDEC) was 39 months after activation of first CI; Boy C (4 years 1 month 5 days) - user of two CIs, last assessment of psychomotor development (PDEC) was 36 months after activation of the first CI.
RESULTS: Analysis of the results from Girl A showed very poor dynamics of development from the age of 12 months, when the first CDS evaluation was performed, up to the PDEC evaluation performed at age 4 years. The CDS score of Boy B showed a very high level of psychomotor development. The PDEC evaluation performed after 39 months of using the first CI showed that the psychomotor development of Boy B was consistent with his chronological age. Boy C presented an average level of psychomotor development (compared to typically developing children) in his CDS scores in the perioperative period and then at 4, 9, and 14 months after cochlear implantation. After 24 months, his CDS scores showed a high level of psychomotor development. After 3 years of CI use, the PDEC evaluation showed that Boy C had an average score in five tested areas, a high score in the area of fine motor skills and lateralization, and a low score in knowledge and learning competencies.
CONCLUSIONS: Children with bilateral profound hearing loss can present different paths of psychomotor development. Children who receive a CI may show an age-appropriate level of psychomotor development compared to typically developing children. However, a hearing, speech, and language rehabilitation specialist responsible for the child still needs to perform regular checkups to monitor all areas of psychomotor development. Also, the effects of the deaf child's environmental determinants on psychomotor development should be studied in detail. These determinants include the parents' emotional state, the parents' involvement in the child's rehabilitation, the family's quality of life, and the presence of deaf siblings. In particular, the difficulties encountered by the mother (or father) in being the parent of a deaf child may hinder the family from receiving adequate support.

PMID: 33348125 [PubMed - as supplied by publisher]

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Carotid artery mobilization prior to pharyngeal flap inset for patients with 22q11.2 deletion syndrome.

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Carotid artery mobilization prior to pharyngeal flap inset for patients with 22q11.2 deletion syndrome.

Int J Pediatr Otorhinolaryngol. 2020 Dec 19;141:110573

Authors: Patel KR, Partain M, Ryan DP, Hersh C, Goldenberg P, Hartnick CJ

Abstract
The management of velopharyngeal insufficiency (VPI) in patients with 22q11.2 deletion syndrome (22q11DS) poses a significant clinical challenge due to presence of a large velopharyngeal gap and a relatively high rate of internal carotid artery (ICA) medialization. To our knowledge, we are the first group to have successfully managed VPI in a series of seven pediatric patients with 22q11DS with medialized ICAs via a novel surgical technique involving carotid artery mobilization followed by pharyngeal flap insertion. Thus far, we have found this technique to be reliably safe with no significant morbidity and caregivers have reported postoperative improvement in speech, swallowing and nasal regurgitation symptoms. Herein, we provide a detailed description of our novel surgical approach, including an instructional video, for correction of VPI in patients with medialized ICAs, who have previously had limited management options.

PMID: 33359933 [PubMed - as supplied by publisher]

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Factors influencing time to operating room in children presenting with post-tonsillectomy hemorrhage.

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Factors influencing time to operating room in children presenting with post-tonsillectomy hemorrhage.

Int J Pediatr Otorhinolaryngol. 2020 Dec 20;141:110581

Authors: Michel M, Preciado D, Allen S, Behzadpour H, Pestieau S, Espinel A

Abstract
OBJECTIVES: We aimed to evaluate factors associated with time to return to OR in children presenting with post-tonsillectomy hemorrhage to a tertiary children's hospital.
METHODS: Retrospective study of pediatric patients presenting to a single institution from January 2012 to January 2020, with post-tonsillectomy hemorrhage (PTH) requiring surgical intervention for control of bleeding. Correlation, univariate, and multivariate analysis were conducted.
RESULTS: Of 15,984 tonsillectomies performed at our institution during the study period, 144 required return to the OR for bleeding control, in addition to 15 other children whose tonsillectomy had been performed at an outside institution. Mean time to the OR was 119.7 min (SD 101.5) in the morning, 77.4 min (SD 60.6) in the afternoon, 55.6 min (SD 34.8) in the evening, and 49.4 min (SD 26.4) overnight (ANOVA p < 0.0001). The mean hemoglobin decline from pre-to post-tonsillectomy was 1.3 g/dl (SD 1.7). Primary hemorrhages had a mean time to OR of 62.39 min (SD 63.42) while secondary hemorrhages mean time to OR was 85.54 min (SD 76.21) (p = 0.0064). There was no significant difference in time to OR among race/ethnicity (p = 0.928), insurance status (p = 0.359), weekday (p = 0.557), surgeon seniority (p = 0.8104) or by hemoglobin drop (p = 0.2773). When controlling for ea ch of these variables, multiple linear regression showed that only time of day had significant correlation with time to OR (p = 0.0003).
CONCLUSION: At a tertiary children's hospital, patients presenting with PTH requiring revision surgery waited the longest to get to the OR in the morning versus all other times of day. These results can aid in individualization of anticipatory guidance in order to reduce morbidity and mortality from complications requiring revision in the operating room.

PMID: 33359934 [PubMed - as supplied by publisher]

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International Pediatric Otolaryngology Group (IPOG) survey: Efforts to avoid complications in home tracheostomy care.

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International Pediatric Otolaryngology Group (IPOG) survey: Efforts to avoid complications in home tracheostomy care.

Int J Pediatr Otorhinolaryngol. 2020 Dec 18;141:110563

Authors: Caloway C, Balakrishnan K, Boudewyns A, Chan KH, Cheng A, Daniel SJ, Fayoux P, Garabedian N, Hart C, Moreddu E, Muntz H, Nicollas R, Nuss R, Pransky S, Rahbar R, Russell J, Rutter M, Sidell D, Smith RJ, Soma M, Spratley J, Thompson D, Ward RF, Watters K, Wyatt M, Zalzal G, Hartnick C

Abstract
OBJECTIVE: To provide guidance for home care tracheostomy management in the pediatric population. The mission of the IPOG is to develop expertise-based recommendations for the management of pediatric otolaryngologic disorders with the goal of improving patient care.
METHODS: Survey of expert opinion by the members of the International Pediatric Otolaryngology Group (IPOG).
RESULTS: Survey results provide guidance for caregiver teaching, the reuse of tracheostomies and suction catheters while inpatient and following discharge, acceptable sterilization practices for tracheostomies, tracheitis workup and management, and outpatient follow-up practices.
CONCLUSION: This presentation of common home tracheostomy care practices are aimed at improving patient-centered care in the pediatric population.

PMID: 33360407 [PubMed - as supplied by publisher]

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Masticatory muscles electrical activity, stress and posture in preadolescents and adolescents with and without temporomandibular dysfunction.

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Masticatory muscles electrical activity, stress and posture in preadolescents and adolescents with and without temporomandibular dysfunction.

Int J Pediatr Otorhinolaryngol. 2020 Dec 15;141:110562

Authors: Miranda LS, Graciosa MD, Puel AN, Raulino de Oliveira L, Sonza A

Abstract
OBJECTIVE: To verify the difference between the masticatory muscles' electrical activity, stress signals and the posture of preadolescents and adolescents with and without temporomandibular dysfunction (TMD).
METHODS: 24 preadolescents and adolescents aged between 11 and 18 years old were divided into two groups, TMD group (TMDG) and control group (CG). All subjects were submitted to anthropometric measurements, psychological stress analysis, temporomandibular joint clinical evaluation and TMD verification; postural evaluation and masseter and temporal muscles electrical activity analysis during chewing. For statistical analysis, the Student's t-test or Mann-Whitney U test were used according to data distribution.
RESULTS: There was a significant difference between the groups for the electrical activity of the right temporal muscles (7.43% ± 2.92 vs. 11.71% ± 5.37) and left (7.70% ± 4.04 vs.11.44% ± 4.03) in the inactive period of chewing between CG and TMDG, respectively. There was no difference in stress or posture variables between groups.
CONCLUSIONS: During the inactive period of chewing, there was greater activation of the temporal muscles in the TMDG. Female gender was prevalent in TMDG. The study participants showed signs of stress, regardless of the group. The posture and TMD relationship still need to be studied.

PMID: 33360408 [PubMed - as supplied by publisher]

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