Study to design stable lansoprazole pellets

Pharmaceutical product development is a complex and creative design process, that involves many factors, many unknowns, many disciplines and has a multiple iterations and a long lifecycle. In the development of pharmaceutical dosage forms, one of persistent challenges is getting an early stability assessment providing an understanding of critical formulation and process parameters. In depth and science based knowledge, whether to use one excipient or another, or to apply one process before the other, could help shortening the process time and as a consequence save the money which is one of the goals of pharmaceutical industry. Pelletization processes are usually lengthy and expensive. Processing of a single batch may sometimes require hours or even days to be completed, and it can result in a non-robust process. Formulation of a stable delivery system for lansoprazole is extremely difficult. Lansoprazole belongs to class II drugs of the Biopharmaceutical Classification System (BCS), characterized by low solubility and high permeability. Furthermore, lansoprazole degrades in a highly acidic and highly basic environment, and it is also unstable under conditions of high temperature and also high humidity, with a decrease in the amount of lansoprazole and discoloration of the material being noted on storage under such conditions Tetsuro et al., 1992. Additionally, a strong pH-dependent solubility of the drug was observed. There is therefore a need for a pharmaceutical delivery system which protects the active substance both during storage as well as the passage through the stomach. The aim of this study was on the one hand the multifactorial investigation of crucial parameters involved in the stability of lansoprazole pellets focusing on the formulation parameters and preparation technique and on the other hand application of Arrhenius equation as a comparative technique in stability of pellets as a solid dosage form. Firstly, thermal characterization of lansoprazole has been conducted in order to clarify the differences reported in the literature and elucidate the reason of the uncommon behaviour when different heating rates were applied. Combining a differential scanning calorimeter (DSC), thermogravimetric analysis (TGA) and hot-stage microscopy (HSM) technique, the results confirmed that the melting point depression at low heating rates was due to eutectic behavior of the drug with its decomposition products formed at low heating rates. Even when the high heating rates (30 and 40°C/min) were applied melting point of lansoprazole did not show independence on the heating rate and difference in the melting point was 1°C. Combination of different techniques and highly dynamic and standardized methods for determination of thermal properties of decomposable substances should be used. Series of experiments were devised to study the effects of various formulation and processing variables on preparation and the stability of lansoprazole in order to examine some of the precautions which can be taken to minimize the loss of activity. Lansoprazole pellets were prepared using two different pelletizing techniques, solution suspension layering in bottom spraying fluidized bed and direct pelletization in rotor processor. Firstly, in a solution suspension layering, influence of type of neutral pellet (sugar based and microcrystalline cellulose based), type of stabilizing agent (influence of neutral and weak basic microenvironmental pH), presence of protective HPMC coating, type of aqueous enteric polymer based on shellac or methacrylic acid copolymer (Marcoat 125® or Eudragit L30 D-55®) and the coating levels on surface morphology, porosity, dissolution and stability of enteric coated pellets containing acid-liable drug, was evaluated. Furthermore, the aim was to investigate the feasibility of rotary processor for preparing lansoprazole loaded pellets based on Balocel®, which is a pre-mixed excipient blend containing microcrystalline cellulose, lactose and sodium carboxymethyl cellulose. Since pelletization in fluidized bed rotary processor is a multivariable process and the final characteristics of produced pellets are affected by several factors, in order to achieve a controlled, robust process and to optimize desired pellet properties, experimental design has been applied using expert design system STAVEX. The most important process variables related to the geometric mean diameter of lansoprazole pellets and the moisture content at the end of liquid addition phase, according to the pre-experiments, included spray rate and rotor speed, while the most influential formulation variable was a level of drug load. The study revealed that even though the process has been optimized to obtain pellets of optimum size and shape, another crucial property of pellets, dissolution, was disregarded and was confounded by another factor which could not be controlled (inlet air humidity) and which was not included in the design. This led to a conclusion, that no matter how comprehensive pre-experimental part of the design is, screening design should be applied. Accelerated degradation, studying the temperature effects in the presence of moisture on the degradation rate constant of lansoprazole in pellets prepared using different pelletization techniques, has been applied. In order to obtain rapid degradation with science based screening approach, Arrhenius equation has been used as a screening and comparative technique to describe a breakdown of lansoprazole in a solid dosage form and it has proved to be helpful tool in obtaining information on the most important formulation parameters and the optimum formulation of lansoprazole pellets for stability. Solution suspension layering technique proved to be more controllable process and more advantageous in terms of pellets size, shape and stability, but more time consuming in comparison to the direct pelletization. Study has confirmed that the key mechanism in obtaining a stabile lansoprazole delivery system is not only suppression of proton attacks but also a limitation of its solubility in the moisture layer, since it was found that in the pellets, lansoprazole degrades following apparent zero-order kinetics. With weak basic microenvironmental pH in the pellets it was possible to keep the degradation and solubility of lansoprazole on a low level. Sugar core stabilized lansoprazole in a way of incorporating the drug in the core forming a less porous active layer on the surface, disabling a contact of water and the active substance. Presence of the protective layer has been justified since it increased the stability of lansoprazole acting as a physical barrier between the drug and the free carboxyl groups of enteric coating polymer. Predicted shelf-lives of pellets on room temperature should be confirmed with the data obtained in a real time stability testing under the same conditions of relative humidity

Post-Covidowy zrównoważony rozwój ekonomiczny

Crises show all the vulnerability and unsustainability of modern economic systems, imposing the need to ask ourselves what really is important, what wealth actually is. At the same time, they are an opportunity to critically review economic systems, ideologies, economic indicators of quality of life and dogmatically set ideas which have negative impacts on society, culture and the environment. In this sense, the current pandemic is an opportunity to take action and make a change, to shift the focus to socio-economic models focused on people, environment and strengthening of global partnership for sustainable development.Kryzysy ukazują wszystkie wady i niezrównoważoność współczesnych systemów ekonomicznych, narzucając potrzebę zadawania pytań o to, co jest naprawdę ważne, czym właściwie jest bogactwo. Jednocześnie kryzysy są okazją do krytycznego przeglądu systemów ekonomicznych, ideologii, ekonomicznych wskaźników jakości życia oraz dogmatycznie ustalonych idei, które mają negatywny wpływ na społeczeństwo, kulturę i środowisko. W tym kontekście obecna pandemia jest okazją do podjęcia działań i wprowadzenia zmian, przesunięcia punktu ciężkości na modele społeczno-gospodarcze skupione na ludziach, środowisku i wzmocnieniu globalnego partnerstwa na rzecz zrównoważonego rozwoju

Disseminated Neonatal Herpes Caused by Herpes Simplex Virus Types 1 and 2

Disseminated neonatal herpes simplex virus (HSV) infection is characterized by progressive multiple organ failure and high mortality rates. It can result from infection with either HSV-1 or HSV-2. We report a case of disseminated neonatal herpes that was caused by HSV-1 and HSV-2

Loss of amphiregulin reduces myoepithelial cell coverage of mammary ducts and alters breast tumor growth

Abstract Background Amphiregulin (AREG), a ligand of the epidermal growth factor receptor, is not only essential for proper mammary ductal development, but also associated with breast cancer proliferation and growth. In the absence of AREG, mammary ductal growth is stunted and fails to expand. Furthermore, suppression of AREG expression in estrogen receptor-positive breast tumor cells inhibits in-vitro and in-vivo growth. Methods We crossed AREG-null (AREG−/−) mice with the murine luminal B breast cancer model, MMTV-PyMT (PyMT), to generate spontaneous breast tumors that lack AREG (AREG−/− PyMT). We evaluated tumor growth, cytokeratin-8 (K8)-positive luminal cells, cytokeratin-14 (K14)-positive myoepithelial cells, and expression of AREG, Ki67, and PyMT. Primary myoepithelial cells from nontumor-bearing AREG+/+ mice underwent fluorescence-activated cell sorting and were adapted to culture for in-vitro coculture studies with AT-3 cells, a cell line derived from C57Bl/6 PyMT mammary tumors. Results Intriguingly, PyMT-induced lesions progress more rapidly in AREG−/− mice than in AREG+/+ mice. Quantification of K8+ luminal and K14+ myoepithelial cells in non-PyMT AREG−/− mammary glands showed fewer K14+ cells and a thinner myoepithelial layer. Study of AT-3 cells indicated that coculture with myoepithelial cells or exposure to AREG, epidermal growth factor, or basic fibroblast growth factor can suppress PyMT expression. Late-stage AREG−/− PyMT tumors are significantly less solid in structure, with more areas of papillary and cystic growth. Papillary areas appear to be both less proliferative and less necrotic. In The Cancer Genome Atlas database, luminal-B invasive papillary carcinomas have lower AREG expression than luminal B invasive ductal carcinomas. Conclusions Our study has revealed a previously unknown role of AREG in myoepithelial cell development and PyMT expression. AREG expression is essential for proper myoepithelial coverage of mammary ducts. Both AREG and myoepithelial cells can suppress PyMT expression. We find that lower AREG expression is associated with invasive papillary breast cancer in both the MMTV-PyMT model and human breast cancer

Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021

IntroductionThe J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries

Post-Covidowy zrównoważony rozwój ekonomiczny

Crises show all the vulnerability and unsustainability of modern economic systems, imposing the need to ask ourselves what really is important, what wealth actually is. At the same time, they are an opportunity to critically review economic systems, ideologies, economic indicators of quality of life and dogmatically set ideas which have negative impacts on society, culture and the environment. In this sense, the current pandemic is an opportunity to take action and make a change, to shift the focus to socio-economic models focused on people, environment and strengthening of global partnership for sustainable development.Kryzysy ukazują wszystkie wady i niezrównoważoność współczesnych systemów ekonomicznych, narzucając potrzebę zadawania pytań o to, co jest naprawdę ważne, czym właściwie jest bogactwo. Jednocześnie kryzysy są okazją do krytycznego przeglądu systemów ekonomicznych, ideologii, ekonomicznych wskaźników jakości życia oraz dogmatycznie ustalonych idei, które mają negatywny wpływ na społeczeństwo, kulturę i środowisko. W tym kontekście obecna pandemia jest okazją do podjęcia działań i wprowadzenia zmian, przesunięcia punktu ciężkości na modele społeczno-gospodarcze skupione na ludziach, środowisku i wzmocnieniu globalnego partnerstwa na rzecz zrównoważonego rozwoju

Baseline level of platelet-leukocyte aggregates, platelet CD63 expression, and soluble P-selectin concentration in patients with posttraumatic stress disorder: a pilot study

Platelets may have an important role in the development of cardiovascular disease (CVD) as a result of chronic stress. We conducted a pilot study to evaluate the effect of posttraumatic stress disorder (PTSD) on baseline platelet activation. Platelet-leukocyte aggregates (PLA) and CD63 expression were measured by flow cytometry, and soluble (s)P-selectin concentration was determined in sera of 20 Croatian male combat veterans with PTSD and 20 healthy civilians. Groups were matched in sex, age, body mass index (BMI) and traditional CVD risk factors. Our data showed no differences in measured parameters. Other platelet activation markers should be determined and a larger sample size used in future studies

12th WINFOCUS world congress on ultrasound in emergency and critical care

Table of contents A1 Point-of-care ultrasound examination of cervical spine in emergency department Yahya Acar, Onur Tezel, Necati Salman A2 A new technique in verifying the placement of a nasogastric tube: obtaining the longitudinal view of nasogastric tube in addition to transverse view with ultrasound Yahya Acar, Necati Salman, Onur Tezel, Erdem Cevik A3 Pseudoaneurysm of the femoral artery after cannulation of a central venous line. Should we always use ultrasound in these procedures? Margarita Algaba-Montes, Alberto Oviedo-García, Mayra Patricio-Bordomás A4 Ultrasound-guided supraclavicular subclavian vein catheterization. A novel approach in emergency department Margarita Algaba-Montes, Alberto Oviedo-García, Mayra Patricio-Bordomás A5 Clinical ultrasound in a septic and jaundice patient in the emergency department Margarita Algaba-Montes, Alberto Oviedo-García, Mayra Patricio-Bordomás A6 Characterization of the eyes in preoperative cataract Saudi patients by using medical diagnostic ultrasound Mustafa Z. Mahmoud, Abdelmoneim Sulieman A7 High-frequency ultrasound in determining the causes of acute shoulder joint pain Mustafa Z. Mahmoud A8 Teaching WINFOCUS Ultrasound Life Support Basic Level 1 for Providers in resource-limited countries Abbas Ali, Alrayah Mustafa, Ihab Abdelrahman, Mustafa Bahar, Osama Ali, H. Lester Kirchner, Gregor Prosen A9 Changes of arterial stiffness and endothelial function during uncomplicated pregnancy Ajda Anzic, Paul Leeson A10 Cardiovascular haemodynamic properties before, during and after pregnancy Ajda Anzic, Paul Leeson A11 An old man with generalized weakness Maryam Bahreini, Fatemeh Rasooli A12 Ultrasonography for non-specific presentations of abdominal pain Maryam Bahreini, Houman Hosseinnejad A13 Introduction of a new imaging guideline for suspected renal colic in the emergency department: effect on CT Urogram utilisation Gabriel Blecher, Robert Meek, Diana Egerton-Warburton A14 Transabdominal ultrasound screening for pancreatic cancer in Croatian military veterans: a retrospective analysis from the first Croatian veteran’s hospital Edina Ćatić Ćuti, Stanko Belina, Tihomir Vančina, Idriz Kovačević A15 The challenge of AAA: unusual case of obstructive jaundice Edina Ćatić Ćuti, Nadan Rustemović A16 Educational effectiveness of easy-made new simulator model for ultrasound-guided procedures in pediatric patients: vascular access and foreign body management Ikwan Chang, Jin Hee Lee, Young Ho Kwak, Do Kyun Kim A17 Detection of uterine rupture by point-of-care ultrasound at emergency department: a case report Chi-Yung Cheng, Hsiu-Yung Pan, Chia-Te Kung A18 Abdominal probe in the hands of interns as a relevant diagnostic tool in revealing the cause of heart failure Ela Ćurčić, Ena Pritišanac, Ivo Planinc, Marijana Grgić Medić, Radovan Radonić A19 Needs assessment of the potential utility of point-of-care ultrasound within the Zanzibar health system Abiola Fasina, Anthony J. Dean, Nova L. Panebianco, Patricia S. Henwood A20 Ultrasonographic diagnosis of tracheal compression Oliviero Fochi, Moreno Favarato, Ezio Bonanomi A21 The role of ultrasound in the detection of lung infiltrates in critically ill patients: a pilot study Marijana Grgić Medić, Ivan Tomić, Radovan Radonić A22 The SAFER Lasso; a novel approach using point-of-care ultrasound to evaluate patients with abdominal complaints in the emergency department Youngrock Ha, Hongchuen Toh A23 Awareness and use of clinician-performed ultrasound among clinical clerkship faculty Elizabeth Harmon, Wilma Chan, Cameron Baston, Gail Morrison, Frances Shofer, Nova Panebianco, Anthony J. Dean A24 Clinical outcomes in the use of lung ultrasound for the diagnosis of pediatric pneumonias Angela Hua, Sharon Kim, James Tsung A25 Effectiveness of ultrasound in hypotensive patients Isa Gunaydin, Zeynep Kekec, Mehmet Oguzhan Ay A26 Moderate-to-severe left ventricular ejection fraction related to short-term mortality of patients with post-cardiac arrest syndrome after out-of-hospital cardiac arrest Jinjoo Kim, Jinhyun Kim, Gyoosung Choi, Dowon Shim A27 Usefulness of abdominal ultrasound for acute pyelonephritis diagnosis after kidney transplantation Ji-Han Lee A28 Lung ultrasound for assessing fluid tolerance in severe preeclampsia Jana Ambrozic, Katja Prokselj, Miha Lucovnik A29 Optic nerve sheath ultrasound in severe preeclampsia Gabrijela Brzan Simenc, Jana Ambrozic, Miha Lucovnik A30 Focused echocardiography monitoring in the postoperative period for non-cardiac patients Asta Mačiulienė, Almantas Maleckas, Algimantas Kriščiukaitis, Vytautas Mačiulis, Andrius Macas A31 POCUS-guided paediatric upper limb fracture reduction: algorithm, tricks, and tips Sharad Mohite A32 Point-of-care lung ultrasound: a good diagnostic tool for pneumonia in a septic patient Zoltan Narancsik, Hugon Možina A33 A case of undergraduate POCUS (r)evolution Sara Nikolić, Jan Hansel, Rok Petrovčič, Una Mršić, Gregor Prosen A34 The Graz Summer School for ultrasound: from first contact to bedside application: three-and-a-half-day undergraduate ultrasound training: résumé after two years of continuous development Simon Orlob, Markus Lerchbaumer, Niklas Schönegger, Reinhard Kaufmann A35 Usefulness of point-of-care ultrasound in the emergency room in a patient with acute abdominal pain Alberto Oviedo-García, Margarita Algaba-Montes, Mayra Patricio-Bordomás A36 Use of bedside ultrasound in a critically ill patient. A case report Alberto Oviedo-García, Margarita Algaba-Montes, Mayra Patricio-Bordomás A37 Diagnostic yield of clinical echocardiography for the emergency physician Alberto Oviedo-García, Margarita Algaba-Montes, Mayra Patricio-Bordomás A38 Focused cardiac ultrasound in early diagnosis of type A aortic dissection with atypical presentation Chun-I Pan, Hsiu-Yung Pan, Chien-Hung Wu A39 Detection of imperforated hymen by point-of-care ultrasound Hsiu-yung Pan, Chia-Te Kung A40 Developing a point-of-care ultrasound curriculum for pediatric nurse practitioners practicing in the pediatric emergency department Sarah Pasquale, Stephanie J. Doniger, Sharon Yellin, Gerardo Chiricolo A41 Use of transthoracic echocardiography in emergency setting: patient with mitral valve abscess Maja Potisek, Borut Drnovšek, Boštjan Leskovar A42 A young man with syncope Fatemeh Rasooli, Maryam Bahreini A43 Work-related repetitive use injuries in ultrasound fellows Kristine Robinson, Clara Kraft, Benjamin Moser, Stephen Davis, Shelley Layman, Yusef Sayeed, Joseph Minardi A44 Lung ultrasonography in the evaluation of pneumonia in children Irmina Sefic Pasic, Amra Dzananovic, Anes Pasic, Sandra Vegar Zubovic A45 Central venous catheter placement with the ultrasound aid: two years’ experience of the Interventional unit, Division of Intensive Care Medicine, KBC Zagreb Ana Godan Hauptman, Marijana Grgic Medic, Ivan Tomic, Ana Vujaklija Brajkovic, Jaksa Babel, Marina Peklic, Radovan Radonic A46 Duplicitas casui: two patients admitted due to acute liver failure Vedran Radonic, Ivan Tomic, Luka Bielen, Marijana Grgic Medic A47 A pilot survey on an understanding of Bedside Point-of-Care Ultrasound (POCUS) among medical doctors in internal medicine: exposure, perceptions, interest, and barriers to training Peh Wee Ming A48 Unusual case of defecation syncope Nur hafiza Yezid, Fatahul Laham Mohammed A49 A case report of massive pulmonary embolism; a multidisciplinary approach Zainal Abidin Huda, Wan Nasarudin Wan Ismail, W.Yus Haniff W.Isa, Hashairi Fauzi, Praveena Seeva, Mohd Zulfakar Mazla

12th WINFOCUS world congress on ultrasound in emergency and critical care.

10.1186/s13089-016-0046-8Crit Ultrasound J8Suppl 112-complete