This study aims to evaluate the long-term effects of parathyroidectomy (PTX) on bone histology, coronary artery calcification, and other biomarkers in hemodialysis patients with severe secondary hyperparathyroidism. A prospective observational study will follow 50 patients undergoing PTX for 12 months, assessing bone biopsies, calcium scoring via CT, and serum biomarkers at baseline and 12 months. The study hypothesizes that PTX will improve bone turnover and mineralization while reducing vascular calcification, aiming to provide insights into long-term PTX outcomes in this patient population.
ICH S7B guideline1 regulates in vitro IKr assay (such as hERG safety assay) and in vitro QT assay for identifying and assessing the potential of a test compound to delay ventricular repolarization. Ventricular repolarization is a complex physiological process determined by the duration of the cardiac action potential. It is the net result of the activities of many highly interdependent membrane ion channels and transporters. Many compounds can affect the activities of the ion channels or transporters, thus have the potential of delaying the ventricular repolarization and leading to prolonged QT interval.
Should patients with refractory anemia with excess blasts or those with oligoblastic AML receive induction therapy prior to allogeneic transplantation?
Yes: Suporn Chancharunee, MD
No: Nina Shah, MD
ICH S7B guideline1 regulates in vitro IKr assay (such as hERG safety assay) and in vitro QT assay for identifying and assessing the potential of a test compound to delay ventricular repolarization. Ventricular repolarization is a complex physiological process determined by the duration of the cardiac action potential. It is the net result of the activities of many highly interdependent membrane ion channels and transporters. Many compounds can affect the activities of the ion channels or transporters, thus have the potential of delaying the ventricular repolarization and leading to prolonged QT interval.
Should patients with refractory anemia with excess blasts or those with oligoblastic AML receive induction therapy prior to allogeneic transplantation?
Yes: Suporn Chancharunee, MD
No: Nina Shah, MD
IDENTIFYING PARATHYROID HORMONE DISORDERS AND ITS PHENOTYPES THROUGH A BONE H...Hussain Karimi
A retrospective analysis of biochemical parameters in bone health screening panel (BHSP) was conducted. The low and high cut offs were applied to determine hypo functioning and hyper functioning conditions related to parathyroid hormone. Clinical phenotypes of parathyroid gland abnormalities were made by using combination of levels of calcium, vitamin D and iPTH. PTH nomogram defined by Harvey et al was applied to calculate max expected PTH for existing level of 25OHD. Medical records of patients were reviewed for clinical validation of biochemical findings.
ABSTRACT- Sickle cell disease (SCD) is an inherited hematological disorder that causes red blood cells to break down continuously. This leads to a rigid, sickle like shape under certain conditions, causing polymerization of the sickled hemoglobin. This study was undertaken to know whether sex hormones (estradiol, progesterone, testosterone and prolactin) exert any effect on the polymerization of sickle cell erythrocytes in vitro and the possibility of these hormones having an effect on the sickling phenomenon. The hemoglobin polymerization test was carried out when hemoglobin S undergoes gelation after it was deprived of oxygen using 2% sodium metabisulphite as reductant. The polymerization inhibition studies were shown that estrogen, progesterone, testosterone and not prolactin had a statistical significant reduction effect (P<0.05) on the polymerization of the sickle cell erythrocytes. The polymerization of the sickle cell erythrocytes was reduced to 50.90%, 62.74%, 67.56% and 92.16% at the concentration of 50.0 pg/ml of estrogen, 5.0 ng/ml of progesterone, 6.0 ng/ml of testosterone and 7.0 ng/ml of prolactin in the same order. This effect was achieved at a low concentration of these hormones. Higher concentrations of the hormones increased polymerization. The result suggests that using the hormones substances at low concentrations can help to ameliorate the intracellular polymerization of sickle cell hemoglobin.
Key-words- Sickle cell, Hormones, Polymerization, Progesterone, Estradiol, Testosterone, Prolactin
International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Anti-Mullerian hormone (AMH) is a glycoprotein, a member of the transforming growth factor-B super family. This hormone is a sensitive marker of ovarian reserve. The present study aims to measure the Anti-Mullerian hormone in thalassemic females receiving the regular blood transfusion as well as patients of chronic idiopathic thrombocgtopenic purpura and age and sex matched controls. Serum Anti-Mullerian hormone was measured by ELISA and Ferritin were measured by RIA. Clinical evaluation was done for all patients including anthropometric measurements, pubertal staging and history taking. Results of the study were analyzed by appropriate statistical methods. Obtained results revealed that the values of Body Mass Index as well as Anti-Mullerian were significantly higher in controls than thalassemics and chronic idiopathic thrombocytopenic purpura and there was a negative correlation between serum Ferritin and Anti-Mullerian hormone. Moreover, Anti-Mullerian hormone was significantly higher in patients receiving Desferal than in those receiving Deferriprone. Reduced Anti-Mullerian hormone in thalassemics as well as chronic ITP patients are considered an important indicator declines in ovarian function which entail modification in the therapeutic plans for thalassemic and chronic ITP patients.
Human Cell Systems Biology for Drug Discovery and Chemical Safety. Presentation at the 7th Brazilian Symposium on Medicinal Chemistry, November 12, 2014, Campos do Jordao-SP, Brazil. Ellen Berg.
Comparative Study of Hscrp in Chronic Kidney Diseaseiosrphr_editor
Chronic kidney disease (CKD) is a global threat to health mainly in developing countries because therapy is expensive and lifelong. over 1 million people worldwide are on dialysis or with a functioning graft. Early detection of Chronic kidney disease (CKD) and its consequent complications can prevent its grave complications . It causes not only significant morbidity but also it causes high mortality. Because of increase in incidence of Diabetes mellitus, hypertension, obesity and an aging population there is increase in progression of chronic kidney disease to end stage renal disease (ESRD). . Cardiovascular disease (CVD) is the major cause of mortality in haemodialysis patients and so it has become imperative to have a screening programme at all levels to detect CKD at an early stage and to initiate specific therapy to reduce the progression of renal disease and also the burden of ESRD (1). High sensitive C-Reactive protein (Hs CRP) assay is useful for sensitive detection of inflammatory state (2,3). This study aims at estimating Hs CRP as a marker of inflammation in CKD patients...
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
1. The long-term effects of parathyroidectomy on Bone histology and coronary
artery calcification in hemodialysis patients: prospective observational study
Osama El-Shahat, Ibrahim El-Zayat, Ahmed Halawa, Hamed Eleraky, Nadia Amr El-Husseini,
Waleed Hassan, Maria Yassen, Florence Lima, Marie Claude Monier-Faugere, Hartmut Malluche
Introduction
Chronic kidney disease-Mineral bone disorder (CKD-MBD) including vascular
calcification, biochemical abnormalities; and renal osteodystrophy increases
morbidity and mortality of dialysis patients.1, 2
Secondary hyperparathyroidism
(SHPT) starts in the early stages of CKD and represents one of the major metabolic
abnormalities in dialysis patients. With dialysis initiation, most patients have
hyperplasia of the parathyroid glands3
and noticeably elevated parathyroid
hormone (PTH) levels4
, which tend to reach higher levels with longer dialysis
vintage. 5, 6
Many observational studies reported that high PTH levels are
associated with increased mortality in this population. 7–14
Since SHPT increases
the chance of renal osteodystrophy and cardiovascular calcification15
, it requires
proper monitoring and timely control of PTH.
2. The medical treatment modalities for SHPT includes oral intestinal phosphate
binders, oral or intravenous (IV) calcitriol or active vitamin D analogs, and
calcimimetic agent either oral (cinacalcet) or IV (etelcalcetide).
Parathyroidectomy (PTX) is an effective treatment option of intractable SHPT
whenever the skillful surgery and nephrology teams are well-trained and available.
Medical treatments are much more expensive and even less available especially in
low and middle-income countries in which PTX could be an appropriate option for
management of severe and resistant SHPT.
The main indications for PTX in dialysis patients are severe uncontrolled
hyperparathyroidism, persistent hypercalcemia and/or hyperphosphatemia.17
Successful PTX lower serum PTH, serum phosphorus, serum calcium. Yajima A et
al. reported that PTX suppresses the bone resorption and enhances bone formation
one week after PTX.17
However, PTX may cause hypoparathyroidism and
excessive reduction of bone turnover, which is associated with poor outcomes in
dialysis patients, including vascular calcification.18
Long-term effect of PTX has not been widely studied yet. Bone turnover status is
worthy to be evaluated in a large number of patients for long duration after PTX.
3. Aim of the study: to evaluate the long-term effects of PTX on:
1- Bone turnover and other bone histomorphometric parameters.
2- Coronary artery calcifications and other cardiovascular calcification parameters.
3- Noninvasive CKD-MBD serum biomarkers.
Inclusion criteria:
1- CKD-5D on regular hemodialysis for at least 6 months.
2- Age of 18 years or older.
3- Serum iPTH level above 1200 pg/dl.
Exclusion criteria:
1- Active malignancy.
2- Liver failure or active liver disease.
3- Active infection.
4- Incompetent patients who are not able to give consent.
5- Any medications that can affect or interact with bone histology as
bisphosphonates, calcitonin, steroid, denosumab, estrogen and fluoride in the
last 6 months.
6- Presence of positive deferoxamine test.
4. 7- Serious gastrointestinal disease, ethanol or drug abuse, chronic
inflammatory disease.
8- Pregnancy or breast-feeding.
9- Corrected serum calcium concentration of less than 7.5 mg/dl.
Study design:
This is a twelve months longitudinal prospective study of 50 patients who will be
subjected to PTX for severe uncontrolled secondary or tertiary HPT. Clinical,
laboratory, multi-slice computed tomography (MSCT) and bone biopsy will be
performed at the time of PTX (baseline) and 12-month thereafter. During the
follow-up, doses of calcitriol, phosphate binders and elemental calcium from
calcium salts will be recorded.
Biochemical parameters:
The following blood biochemical parameters will be determined: (1) iPTH and
whole PTH; (2) BSAP (3) PINP, (4) TRAP-5b, (5) RANK-L and OPG, (6)
Sclerostin, (7) FGF-23, (8) Soluble Klotho, (9) Activin-A, (10) Fetuin-A and (11)
CTX.
(1) iPTH and whole PTH Assays: iPTH will be measured by a
radioimmunometric assay (RIA) (Scantibodies, Santee, CA): normal range is 14 to
5. 66 pg/ml; intra- and inter-assay coefficients of variation are <5 and <7%,
respectively.
(2) Bone specific alkaline phosphatase (BSAP): Serum BAP levels will be
measured using an enzyme immunoassay (EIA) (Metra BAP EIA (Quidel San
Diego, CA). Normal serum BAP levels range are 18-75 U/L; intra- and inter-assay
coefficients of variation are <6% and <8%, respectively.
(3) Procollagen type I N-terminal propeptide (PINP): Total P1NP levels will be
measured using an ELISA (USCNK, Wuhan, China); the intra- and interassay
coefficients of variation are ,9% and ,10%, respectively.
(4) Tartrate resistant acid phosphatase 5b (TRAP-5b): levels will be determined
using an EIA (MicroVue,/Quidel, Santa Clara, CA). Normal serum levels range are
1.2-6.7 U/L; intra- and inter-assay coefficients of variation are <2.2% and <3%,
respectively.
(5) Receptor activator of nuclear factor kappa ligand (RANK-L) and
Osteoprotegerin (OPG): Levels will be determined using an enzyme-linked
immunosorbent assay (ELISA) (Alpco, Windham, NH). The normal range for
RANK-L is 1–50 pmol/L and the intra- and inter-assay coefficients of variation are
<5% and <9%, respectively. The normal range for Osteoprotegerin (OPG) is 1–30
6. pmol/L and the intra- and inter-assay coefficients of variation are <10%,
respectively.
(6) Sclerostin: Serum sclerostin levels will be measured using an EIA
(Tecomedical Group, Sissach, Switzerland). The intra- and interassay coefficients
of variation are,3.1% and 3.5%, respectively.
(7) FGF-23: Serum intact FGF-23 levels will be measured using two-site
immunosorbent assay (ELISA) kit (Kainos Laboratories, Tokyo, Japan). Two
specific murine monoclonal antibodies bind to full-length FGF-23. One antibody is
immobilized onto the microtiter plate well for capture. The other antibody is
conjugated to horseradish peroxidase (HRP) for detection. Normal range for
FGF23 is 18-108 pg/mL. The kit has a high sensitivity with the minimum detection
limit of 3 pg/mL as well as a wide quantification range of 3-800 pg/mL. Each
sample will be assessed in triplicate. With concentrations > 800 pg/mL, the
procedure will be repeated using a 1/10 dilution.
(8) Klotho: Serum Klotho will be measured using enzyme-linked ELISA kit
(Immuno Biological Laboratories Co., Ltd., Japan). Mean values for the inter- and
intra-assay coefficients of variability are 6.5% ± 3.3% and 3.6% ± 1.5%,
respectively.
7. (9) Activin-A: Activin-A levels will be measured by ELISA, R&D Systems Inc,
Minneapolis, USA—sensitivity 3.67 pg/mL, intra- and inter-assay coefficient
variation of 4.2-4.4 % and 4.7–7.9 %, respectively.
(10) Fetuin-A: Serum fetuin-A will be measured using a quantitative sandwich
enzyme immunoassay technique (R&D Systems Inc MINN), with reported intra-
and inter-assay coefficient variations of 4.0 and 8.4 %, respectively, and sensitivity
0.62 ng/ml.
Bone Biopsies:
Bone biopsies will be performed in all patients at baseline and 12 months later.
Different tetracycline compounds (tetracycline hydrochloride and demeclocycline
hydrochloride) will be used to distinguish timed bone labels. Tetracycline
hydrochloride gives a yellow color and demeclocycline hydrochloride
(Declomycin®, Lederle, Wayne, NJ), a golden-yellowish fluorescence under
fluorescent light microscopy. The labeling schedule consists of a 2-day oral
administration of tetracycline hydrochloride (250 mg bid) followed by a drug-free
interval of 10 days and subsequent oral administration of demeclocycline
hydrochloride (150 mg bid) for 4 days. The bone biopsy will be performed 2-4
days after the last demeclocycline dose. This dosing regimen is adjusted for CKD-
5D patients. The investigators will provide study participants with a calendar
8. indicating the date of the bone biopsy and dates on which the compounds should
be taken. She will also call study participants on the respective dates to remind
them to take the medication. Study participants will undergo local anesthesia using
Lidocaine 1% and sedation and pain management with Versed® and fentanyl or
propofol as deemed necessary by Mansoura international hospital anesthesiologist.
Bone samples will be taken from the anterior iliac crest by the one-step electrical
drill technique (Straumann Medical, Waldenburg, Switzerland). This biopsy
technique will be done by Dr. Ibrahim El-Zayat and his colleagues. Bone
specimens will be shipped to University of Kentucky Bone histomorphometric lab.
Mineralized Bone Histology:
Iliac crest bone samples will be fixed in 100% ethanol at room temperature,
dehydrated and embedded in methylmethacrylate as previously described. Serial
sections of 3- and 7-μm thicknesses will be cut with a Microm microtome, model
HM360 (Microm, C. Zeiss, Thornwood, NY). Sections will be stained with the
modified Masson-Goldner trichrome stain and the aurin tricarboxylic acid stain to
measure the extent of aluminum deposits at the bone-osteoid interface, with
solochrome azurine stain used as control and for detection of aluminum within
bony trabecules, and with the modified Gomori trichrome stain for detection of
iron. Unstained sections will be prepared for phase contrast and fluorescent light
microscopy.
9. Bone Histomorphometry:
Cellular and dynamic parameters of bone structure, formation, and resorption will
be evaluated at standardized sites in cancellous and cortical bone using the
semiautomatic method (Osteoplan II, Kontron, Munich, Germany) at a
magnification of 200x.
The following parameters are selected for evaluation of bone turnover: (1)
activation frequency (yr-1), and (2) bone formation rate / bone surface
(mm3/cm2/yr). These parameters are obtained separately in cortical and cancellous
bone. Bone volume / tissue volume (BV/TV) (%) will be used for evaluation of
bone volume. Mineralization will be assessed by osteoid thickness (OT) and
mineralization lag time (MLT). Osteomalacia, is defined as osteoid thickness > 20
µm and mineralization lag time > 100 days. These parameters comply with the
guidelines of the nomenclature committee of the American Society of Bone and
Mineral Research. The Osteoplan II software has been programmed to transfer data
automatically to the statistical software SPSS for Windows (SPSS; Chicago IL).
Bone turnover and volume parameters will be entered as continuous variables in
statistical analyses.
Multi-slice Computed Tomography (MSCT):
10. Coronary artery calcium (CAC), thoracic aorta calcium (TAC) and abdominal
aorta calcium (AAC) scores will be assessed by using MSCT of the heart and
aorta. Non-contrast computed tomography of chest & abdomen for calcium scoring
will be performed on a Dual Source 128 Slice CT scanner (Siemens AG, Erlangen,
Germany). For CAC and TAC scores, images will be acquired from carina to the
LV apex, and the AAC images will include the distal 8 cm long segment of the
aorta ending at the aortic bifurcation as described by Multi-Ethnic Study of
Atherosclerosis (MESA) investigators. Scan parameter will be the following: ECG
gating, 64 x 0.6 collimation, 120 kVp, 80 mAs/rotation, 0.33 sec gantry rotation
time and 3 mm slice thickness. Images will be analyzed on a 3D workstation using
calcium scoring software (HeartView CT, Siemens AG, Erlangen, Germany). For
all calcium measurements (i.e., CAC, TAC, and AAC), calcification will be
identified as a plaque of ≥1 mm2 with a density of ≥130 HU and quantified using
the previously described Agatston scoring method. Image acquisition will be
performed locally in Mansoura international hospital under the supervision of the
Cardiac Radiologist. He will then read the scans and provide calcification scores to
the investigators.
11. Timeline:
1) IRB approval 2 months
2) Setups/ initiation of study/ patients recruitment 2 month
3) Run in time 12 months
4) Analysis 3 months
Statistical analysis:
Power Calculations:
Based on preliminary studies, bone formation rate/bone surface (BFR/BS) has the
highest variability among bone histomorphometric parameters (unpublished data).
We anticipate that the mean difference in BFR/BS between the two groups will be
7.4 µm3/µm2/yr (i.e., 10.8 vs. 3.4 µm3/µm2/yr). With an alpha level of 0.05 and a
sample size of 50 patients, the study will have a power of 80% to yield statistically
significant results.
Analysis of results:
Results will be expressed as mean ± SEM. All statistical tests will be two-sided.
An assigned significance level of 0.05 will be used. Normality of distribution will
be assessed by the Lilliefors test and homogeneity of variance with the Levene test.
12. Appropriate transformations of the data will be done when results do not meet
assumptions for normality.
Results will be compared between the before and after using two-way analysis of
variance (ANOVA) for pre-post measurements of BFR/BS and bone biomarkers
levels. The Kruskal Wallis test will be used to compare CACs and Aortic calcium
contents. All computations will be performed using the SPSS software package for
Windows, release 23 (SPSS, Chicago, IL).
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