This document discusses assays used to measure vitamin D and its metabolites in the body. It begins by providing background on vitamin D metabolism, with vitamin D obtained from sunlight or diet and undergoing hydroxylation in the liver and kidneys to become biologically active. Current assays measure circulating levels of vitamin D, 25-hydroxyvitamin D (25-OH-D), or 1,25-dihydroxyvitamin D (1,25(OH)2D). The 25-OH-D assay is most useful for determining overall vitamin D status as it reflects both dietary and sunlight exposure. Measurement of 1,25(OH)2D is useful for evaluating disorders in calcium metabolism related to errors in its production. Assays have advanced
Vitamin D deficiency is widespread in both the pediatric and adult chronic kidney disease CKD population. CKD is characterized by dysregulation of vitamin D and mineral metabolism. Secondary hyperparathyroidism and its management puts patients with CKD at increased cardiovascular risk. Emergence of experimental and some clinical data suggesting beneficial effects of vitamin D on proteinuria, blood pressure, inflammation and cardiovascular outcomes has pushed it to the center stage of CKD research. Pediatric data on vitamin D dysregulation and its consequences are still in its infancy. Ongoing prospective studies such as Chronic Kidney disease in Children CKiD and the Cardiovascular Comorbidity in Children with CKD 4 C should help to delineate the evolution of disturbances in mineral metabolism and its adverse effects on growth, CKD progression and cardiovascular outcomes. Dr. Prafull Dawale | Neha Jain "Vitamin D in Chronic Kidney Disease" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-5 , August 2019, URL: https://www.ijtsrd.com/papers/ijtsrd26778.pdfPaper URL: https://www.ijtsrd.com/medicine/other/26778/vitamin-d-in-chronic-kidney-disease/dr-prafull-dawale
Vitamin D- Introduction , source, synthesis of vitamin D in body, absorption of vitamin D in the body , action of vitamin D,
vitamin D deficiency & toxicity, Dietary reference value,
Vitamin D deficiency is widespread in both the pediatric and adult chronic kidney disease CKD population. CKD is characterized by dysregulation of vitamin D and mineral metabolism. Secondary hyperparathyroidism and its management puts patients with CKD at increased cardiovascular risk. Emergence of experimental and some clinical data suggesting beneficial effects of vitamin D on proteinuria, blood pressure, inflammation and cardiovascular outcomes has pushed it to the center stage of CKD research. Pediatric data on vitamin D dysregulation and its consequences are still in its infancy. Ongoing prospective studies such as Chronic Kidney disease in Children CKiD and the Cardiovascular Comorbidity in Children with CKD 4 C should help to delineate the evolution of disturbances in mineral metabolism and its adverse effects on growth, CKD progression and cardiovascular outcomes. Dr. Prafull Dawale | Neha Jain "Vitamin D in Chronic Kidney Disease" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-5 , August 2019, URL: https://www.ijtsrd.com/papers/ijtsrd26778.pdfPaper URL: https://www.ijtsrd.com/medicine/other/26778/vitamin-d-in-chronic-kidney-disease/dr-prafull-dawale
Vitamin D- Introduction , source, synthesis of vitamin D in body, absorption of vitamin D in the body , action of vitamin D,
vitamin D deficiency & toxicity, Dietary reference value,
Vitamin D deficiency is of concern now a days, it has important role in skeletal and non skeletal functions of the body. Good sunlight exposure, consumption of vitamin D rich foods, chemotherapy with vitamin D and supplements of vitamin D has shown positive effect on various non skeletal diseases like cancer, diabetes, diarrhoea, tuberculosis etc. Although Indians are blessed with ample sunlight, still 70 to 100% population is suffering from the vitamin D deficiency. Vitamin D deficiency is likely to play an important role in the very high prevalence of rickets, osteoporosis, cardiovascular diseases, diabetes, cancer and infections such as tuberculosis in India. Fortification of staple foods with vitamin D is the most viable population based strategy to achieve vitamin D sufficiency. Unfortunately, even in advanced countries like USA and Canada, food fortification strategies with vitamin D have been only partially effective and have largely failed to attain vitamin D sufficiency
Hydration and Fluid Replacement
Fluid in take is the most important nutritional factor during competition . Dehydration is a concern during any physical activity. Athletes should aim to drink regularly rather then wait until they become thirsty as thirst is often a poor indicator of hydration.
Fluid requirements vary remarkably between athletes and between exercise situations. Fluid losses and the onset of dehydration are affected by:
Genetics - some people innately sweat more than others
Body Size - larger athletes tend to sweat more than smaller athletes
Fitness - fitter people sweat earlier in exercise and in larger volumes
Environment - sweat losses are higher in hot, humid conditions
Exercise Intensity - sweat losses increase as exercise intensity increases
Generally athletes should aim to drink 150- 250mls of water every 15 minutes
Fluid Losses
General Fluid Replacement Guidelines
Immediately, before exercise commences, consume 200-600 ml of fluid.
Develop a plan for fluid intake for all exercise sessions longer than 30 minutes. Aim to match previous fluid losses as closely as possible (within 1% of body mass). Take into account all the opportunities within the sport.
Begin drinking early in the exercise session and continue to drink small amounts regularly. Sports drink or water are the best options.
Aim to replace fluids as they are lost
(http://www.ausport.gov.au/ais/nutrition/factsheets/hydration2/fluid_-_who_needs_it)
General Fluid Replacement Guidelines cont.
Drink plenty of water after exercise, past the point of quenching your thirst
Avoid drinking tea, coffee, cola drinks and alcohol after training or games
Glucose are not recommended as they can speed up the onset of dehydration
Sports drinks should only be taken in small amounts before a sport to prevent the early use of glycogen stores
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- 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
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
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
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.
Follow us on: Pinterest
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
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
2. VITAMIN D ASSAYS 1465
VITAMIN D cutaneous production of previtamin D3 include sea
sonal changes, time of day, skin pigmentation, aging,
and sunscreen use (10-14).
The other major source of vitamin D is from the
Liver
VITAMIN D-25- diet. In the United States and Canada, the ingestion
hydroxylase
of fortified milk, which contains 400 IU (10 ¿ig) of
either ergocalciferol or cholecalciferol per quart, pro
vides twice the United States recommended daily al
PO.ond
lowance (USRDA) of 200 IU for this essential fat-sol
OTHER FACTORS uble substance. The only other major dietary source
of vitamin D is from fatty fish and fish liver oils.
Vitamin D concentrations were first measured by
rat and chick bioassays (15-17). The rat bioassay,
1,25-(OH),-D commonly known as the line test, was widely used to
determine the concentration of vitamin D in fortified
foods (15). The development of specific assays for vi
tamin D and its biologically important metabolites
made these bioassays obsolete.
The half-life of circulating vitamin D is only 24 h
(18). Thus, the serum concentration at any time is de
pendent on times of the most recent ingestion of vi
Downloaded from jn.nutrition.org by on June 11, 2008
tamin D as well as of the last exposure to sunlight (18,
19). The quot;normalquot; range of serum vitamin D is 0-310
nmol/L (0-120 ng/mL) (18-20). Consequently serum
ergocalciferol or cholecalciferol is of little value in de
termining the vitamin D status of a patient. Nonethe
less, serum vitamin D assays are useful for determining
the capacity of human skin to produce vitamin D in
response to exposure to solar or simulated solar ultra
violet radiation (18). Furthermore, the measurement
FIGURE I Schematic representation of the hormonal of circulating concentrations of vitamin D 12-24 h
control loop for vitamin D metabolism and function. A re after an oral dose of 50,000 IU (1.25 mg) of ergocal
duction in the serum calcium below ~8.8 mg/mL prompts
a proportional increase in the secretion of parathyroid hor
ciferol provides valuable clinical information for de
mone, which enhances the mobilization of calcium stores termining whether a patient with a malabsorption
from bone. Parathyroid hormone also promotes the synthesis syndrome can absorb vitamin D (20) (Fig. 3).
of 1,25(OH)2D in the kidney, which, in turn, stimulates the Plasma and serum concentrations of vitamin D are
mobilization of calcium from the bone and its absorption determined by: 1) extracting the lipid-soluble vitamin
from the intestine. Reproduced with permission (38). D from 1 to 2 mL of serum or plasma, 2) separating
vitamin D from its metabolites and lipid contaminants
in the extract by rapid reverse-phase cartridge chro-
ceptor (1-3, 7). These insights have been of great value matography, 3) further resolving the vitamin D frac
for the pharmacologie use of 1,25(OH)2D3 in the hy- tion by straight phase high-performance liquid chro-
perproliferative skin disorder psoriasis (7-9). matography (HPLC), and 4) quantitating the amount
of vitamin D by its ultraviolet absorbance in the HPLC
eluate or by a competitive protein binding assay (18,
21-23). The intra-assay and interassay variations are
PHOTOSYNTHESIS, ABSORPTION, ~10 and 12%, respectively.
AND ASSAYS FOR VITAMIN D
Sunlight, which contains wavelengths between 290
and 315 nm, photolyzes provitamin D3 (7-dehydro- DETERMINATION AND CLINICAL UTILITY
cholesterol) in the skin to previtamin D3 (Fig. 2). Pre OF THE CIRCULATING CONCENTRATION
vitamin D3, a thermally labile compound, undergoes OF 25-HYDROXYVITAMIN D
an internal isomerization of its double bonds to form
the thermodynamically stable vitamin D3 (2), which The half-life of circulating 25-OH-D is ~3 wk (2).
is then translocated from the epidermis into the dermal Therefore, its steady-state concentration summates the
capillary bed (Fig. 2). Factors that can influence the concentrations of vitamin D derived both from the
3. 1466 HOLICK
SUN
SUN
7- DEHYDROCHOLESTEROL
Downloaded from jn.nutrition.org by on June 11, 2008
BLOOD
DBP-D3 DBP
FIGURE 2 Schematic representation of the formation of previtamin D3 in the skin during exposure to the sun, the thermal
isomerization of previtamin D3 to vitamin D3/ and the specific translocation of vitamin D3 by the vitamin D-binding protein
(DBP) into the circulation. During continual exposure to the sun, previtamin D3 also photoisomerizes reversibly to Iumisterol3
and tachysterol3, which are biologically inert photoproducts (i.e., they do not stimulate intestinal calcium absorption). Because
the DBP has no affinity for Iumisterol3 and has minimal affinity for tachysterol3/ the translocation of these photoisomers into
the circulation is negligible. Subsequently, these photoproducts are sloughed off during the natural turnover of the skin.
When previtamin D3 stores are depleted (due to its thermal isomerization to D3), however, lumisterol and tachysterol, upon
exposure to UV radiation, will photoisomerize to preD3. Reproduced with permission of the American Association for the
Advancement of Science (39).
diet and from photo-formation over a several weeks is considered to be normal. Vitamin D intoxication is
to several months. The separate measurement of 25- usually associated with 25-OH-D concentrations
OH-cholecalciferol and 25-OH-ergocalciferol was above 375 nmol/L (150 ng/mL), with attendant hy-
originally thought to provide information about sun percalcemia and hyperphosphatemia (2).
light-induced vs. dietary sources of vitamin D (24). Serum concentrations of 25-OH-D are measured in
However, since milk and multivitamin preparations several ways (25-30). A competitive protein-binding
are now fortified with both forms of the vitamin, the assay is often used. The vitamin D-binding protein,
separate measurement of these metabolites is of little which has a very high affinity for 25-OH-D (26-28),
value. binds the ligand in a lipid extract of serum or plasma
The 25-OH-D assay is most valuable for determin (0.1 mL). However, other vitamin D metabolites can
ing the vitamin D status of an individual. For its assay, interfere with this assay, even though they usually
commercial diagnostic laboratory services and assay represent <10% of the total binding activity (29). To
kits are available. The normal circulating concentra increase the specificity, 25-OH-D can first be separated
tion of 25-OH-D is usually reported to be between 20 from vitamin D and its metabolites by a rapid straight-
nmol/L (8 ng/mL) and 150 nmol/L (60 ng/mL). Serum phase silica cartridge chromatography (30), followed
values below 25 nmol/L (10 ng/mL) are generally con by the competitive protein-binding assay.
sidered to indicate impending or frank vitamin D de Circulating concentrations of 25-OH-ergocalciferol
ficiency. Although most diagnostic laboratories report and 25-OH-cholecalciferol can be accurately measured
the upper limit of the normal range for 25-OH-D to by first chromatographing a lipid extract from 1 mL
be 150 nmol/L (60 ng/mL), circulating concentrations of serum or plasma on a rapid straight-phase or reverse-
of 250 nmol/L (100 ng/mL) in lifeguards after a full phase cartridge followed by straight-phase HPLC. The
summer of exposure to sunlight is not uncommon and amounts of 25-OH-ergocalciferol and 25-OH-chole-
4. VITAMIN D ASSAYS 1467
80 n 1,25(OH)2D receptor recognizes l,25(OH)2cholecal-
ciferol better than l,25(OH)2ergocalciferol (2, 29). As
a result, this assay underestimated the total circulating
concentration of 1,25(OH)2D. This assay has been im
proved by using the bovine thymus 1,25(OH)2D re
ceptor (29, 33), which reacts equally well with
l,25(OH)2ergocalciferol and l,25(OH)2cholecalciferol.
In addition, the HPLC step has now been replaced by
a rapid silica cartridge Chromatographie step (34, 35).
A bioassay using cultured rat calvarÃ-a an detect pi-
c
cogram quantities of 1,25(OH)2D in the circulation
(36). However, this assay is very time consuming and
requires a tissue culture facility. It is most useful in
verifying the results from a competitive receptor
binding assay.
The half-life of circulating 1,25(OH)2D has been es
24 48 72
timated to be between 4 and 6 h (37). The normal range
HOURS of serum values is between 38 and 144 pmol/L (16-
FIGURE 3 Serum vitamin D concentrations in seven pa 60 pg/mL). As vitamin D deficiency develops, the body
tients with diarrheal syndromes after a single oral dose of responds by increasing the production and secretion
Downloaded from jn.nutrition.org by on June 11, 2008
50,000 IU (1.25 mg) of ergocalciferol. For comparison, the of parathyroid hormone (Fig. 1). Parathyroid hormone
means and standard errors of vitamin D concentrations in turn enhances the 1-hydroxylation of 25-OH-D (1-
measured in seven normal control subjects after a similar 3) (Fig. 1). Thus, secondary hyperparathyroidism ac
dose are indicated by the closed circles and dotted lines celerates the conversion of 25-OH-D to 1,25(OH)2D
(— •€”). Note that two patients, one with Crohn's ileo-
â
colitis (patient F) and one with ulcerative colitis (patient G),
(1-3). Since the circulating concentration of 25-OH-
had essentially normal absorption curves. Five patients, D is about three orders of magnitude higher than
however, showed a dramatic lack of response, with no values 1,25(OH)2D, even very low levels of 25-OH-D can
above 10 ng/mL. Reproduced with permission (20). provide enough substrate for the formation of some
1,25(OH)2D. In vitamin D deficiency, vitamin D is
also efficiently converted to 25-OH-D (18). As a result,
calciferol in the eluate are quantitatively determined a hospital patient with vitamin D deficiency who has
by their UV absorption at either 254 or 265 nm (21, previously obtained a very small quantity of vitamin
25, 29, 30). D from food or exposure to sun can have low or un-
The assay for serum 25-OH-D has clinical utility detectable circulating concentrations of 25-OH-D
in determining the vitamin D status of patients with while having low, normal, or even high circulating
intestinal malabsorption syndromes or with severe concentrations of 1,25(OH)2D (1, 2, 18, 38). Thus
hepatic failure, as well as of the very young and the serum 1,25(OH)2D concentrations are of little value
elderly (2), who may be at risk of vitamin D deficiency. in the evaluation of vitamin D deficiency. Needless to
say, in an absolute vitamin D deficiency state, circu
lating concentrations of 1,25(OH)2D are undetectable.
DETERMINATION AND CLINICAL UTILITY The measurement of circulating concentrations of
OF THE CIRCULATING CONCENTRATION 1,25(OH)2D have been of great value to clinicians for
OF 1,25-DIHYDROXYVITAMIN D the evaluation of patients with acquired and inherited
disorders of 1,25(OH)2D metabolism (1-3, 29, 38).
Specific assays for 1,25(OH)2D (29, 31-33) in serum Serum 1,25(OH)2D levels are routinely assayed by
and plasma are based on the separation of minute commercial diagnostic laboratories and can be mea
quantities of 1,25(OH)2D from lipid contaminants and sured as well by assay kits. Patients with chronic
other vitamin D metabolites. The concentration of renal failure, hyperphosphatemia, hypoparathyroid-
l,25(OH)2cholecalciferol is then determined by a ism, pseudohypoparathyroidism, tumor-induced os
competitive receptor binding assay using a nuclear/ teomalacia, hypercalcemia of malignancy (in most
cytosolic receptor for 1,25(OH)2D (31-33). Initially cases), or vitamin D-dependent rickets type I [an in
1,25(OH)2D in a lipid extract of 2 to 3 mL of serum born error that markedly reduces the conversion of
or plasma was separated from other vitamin D metab 25-OH-D to 1,25(OH)2D] often have low circulating
olites by straight phase HPLC. The 1,25(OH)2D frac concentrations of 1,25(OH)2D (2, 29, 38). Serum con
tion was then subjected to a competitive protein-bind centrations of 1,25(OH)2D are elevated above the nor
ing assay that used the chick cytosolic 1,25(OH)2D mal range in patients with primary hyperparathyroid
receptor (31, 32). However, the chick intestinal ism, vitamin D-dependent rickets type II; [an inborn
5. 1468 HOLICK
error in which the recognition of 1,25(OH)2D by target 11. WEBB, A. R., KLINE, L. & HOLICK, M. F. (1988) Influence of
tissue receptors is defective]; chronic granulomatous season and latitude on the cutaneous synthesis of vitamin D3 :
exposure to winter sunlight in Boston and Edmonton will not
disorders such as sarcoidosis, tuberculosis, and sili promote vitamin D3 synthesis in human skin. /. Clin. Endocrino!.
cosis; and lymphoma (in some patients) (2, 29, 38). Metab. 67: 373-378.
12. CLEMENS, . L., HENDERSON, . L., ADAMS,J. S. &.HOLICK,M. F.
T S
(1982) Increased skin pigment reduces the capacity of skin to
synthesize vitamin D3. Lancet 74-76.
CONCLUSION 13. HOLICK,M. F., MATSUOKA,L. Y. & WORTSMAN,J. (1989) Age,
vitamin D, and solar ultraviolet radiation. Lancet ii: 1104-1105.
14. MATSUOKA,L. Y., IDE, L., WORTSMAN,J., MACL.AUGHLIN, . & J
Vitamin D is essential for the maintenance of cal HOLICK, M. F. (1987) Sunscreens suppress cutaneous vitamin
cium and bone metabolism throughout our lives. The D3 synthesis. /. Clin. Endocrino!. Metab. 64: 1165-1168.
major source of vitamin D is casual exposure to sun 15. STEENBOCK, & BLACK,A. (1924) The reduction of growth-
H.
light. In the absence of exposure to sunlight, the av promoting and calcifying properties in a ration by exposure to
erage daily requirement for vitamin D is probably 2 ultraviolet light. /. Bio!. Chem. 61: 408-422.
16. STEENBOCK, . & KLETZIEN,S. W. F. (1932) The reaction of
H
to 3 times higher than the USRDA of 200 IU (5 fig)
chickens to irradiated ergosterol and irradiated yeast as con
(Paris, P., Bondi, K., Luria, S. and Holick, M. F., un trasted with the natural vitamin D in fish liver oil. /. Bio!. Chem.
published results). Among assays for vitamin D and 97: 249-264.
its metabolites, the assay of serum 25-OH-D levels 17. WADDELL,J. (1934) The provitamin D of cholesterol. I. The
has the most utility for determining the vitamin D antirachitic efficacy of irradiated cholesterol. /. Bio!. Chem. 105:
711-739.
status of an individual. Circulating concentrations of
18. CLEMENS, . L., ADAMS,J. S. & HOLICK,M. F. (1982) Measure
T
vitamin D and of 1,25(OH)2D, however, can be of
Downloaded from jn.nutrition.org by on June 11, 2008
ment of circulating vitamin D in man. Clin. Chim. Acta 121:
value for clinicians who are evaluating malabsorption 301-308.
syndromes and acquired and inherited disorders of 25- 19. ADAMS,J. A., CLEMENS,T. L., PARRISH,J. A. & HOLICK, M. F.
OH-D metabolism, respectively (1-3, 29, 38). (1981) Vitamin D synthesis and metabolism after ultraviolet
radiation of normal and vitamin D deficient subjects. N. Eng!.
/. Med. 306: 722-725.
20. Lo, C. W., PARIS,P. W., CLEMENS, . L., NOLAN, J. &. HOLICK,
T
M. F. (1985) Vitamin D absorption in healthy subjects and in
LITERATURE CITED
patients with intestinal malabsorption syndromes. Am. J. Clin.
Nutr. 42: 644-649.
1. DELuCA, H. (1988) The vitamin D story: a collaborative effort 21. JONES,G. (1978) Assay of vitamin D2 and D3 in human plasma
of basic science and clinical medicine. FASEB /. 2: 224-236.
by high performance liquid chromatography. Clin. Chem. 24:
2. HOLICK,M. F. (1989) Vitamin D: biosynthesis, metabolism, and 287-298.
mode of action. In: Endocrinology, pp. 902-926, vol. 2,
22. CHEN, T. C., TURNER, A. K. & HOLICK,M. F. (1990) A method
(DeGroot, L. }., CahUl, G. F. Jr., Martini, L., Nelson, D. H., for the determination of the circulating concentration of vitamin
Odell, W. D., Potts, J. T. Jr., Steinberger, E., and Winegrad, D. /. Nutr. Biochem. (in press).
A. I., eds.) Gruñeand Stratton, New York. 23. HOLLIS,B. W., Roos, B. A. & LAMBERT, . W. (1981) Vitamin
P
3. REICHEL,H., KOEFFLER, P. & NORMAN,A. W. (1989) The role
H.
D in plasma: quantitation by a nonequilibrium ligand binding
of the vitamin D endocrine system in health and disease. N. assay. Steroids 37: 609-619.
Engl./. Med. 320:981-991.
24. HADDAD, H. G. & HAHN, T. J. (1973) Natural and synthetic
4. STUMPF,W. E., SAR, M., REID, F. A., et al. (1979) Target cells sources of circulating 25-hydroxyvitamin D in man. Nature 244:
for 1,25-dihydroxyvitamin D3 in intestinal tract, stomach, kid
515-517.
ney, skin, pituitary, and parathyroid. Science 206: 1188-1190.
25. CHEN, T., TURNER, A. & HOLICK,M. F. (1990) Method for de
5. TSOUKAS, . D., PROVVEDINE, M. &.MANOLAGAS, C. (1984)
C D. S. termination of the circulating concentration of 25-hydroxyvi
1,25-Dihydroxyvitamin D3, a novel immuno-regulatory hor
mone. Science 221: 1438-1440. tamin D. /. Nutr. Biochem. (in press).
6. BHALLA,A. K., CLEMENS,T., AMENTO, E., HOLICK, M. F. &. 26. HADDAD,J. G. & CHUY,K. J. (1971 ) Competitive protein binding
KRANE, S. M. (1983) Specific high-affinity receptors for 1,25- radioassay for 25-hydroxycholecalciferol. /. Clin. Endocrinol.
Metab. 33: 992-995.
dihydroxyvitamin D3 in human peripheral blood mononuclear
cells: presence in monocytes and induction in T lymphocytes 27. BELSEY, ., CLARK,M. B. BERNAT,M., GLOWACKI,J., HOLICK,
R
following activation. /. Clin. Endocrino!. Metab. 57: 13008- M. F., DELUCA, H. F. & POTTS, J. T. (1974) The physiologie
13010. significance of plasma transport of vitamin D and metabolites.
7. HOLICK,M. F. (1989) 1,25-Dihydroxyvitamin D3 and the skin: Am. /. Med. 57: 50-56.
a unique application for the treatment of psoriasis. Proc. Soc. 28. HOLLIS,B. W., BURTON,J. H. & DRAPER,H. H. (1977) Abinding
Exper.Med. 19:246-257. assay for 25-hydroxycalciferol and 24R,25-dihydroxycalciferols
8. MORIMOTO,S. & KUMAHARA, . (1985) A patient with psoriasis
Y using bovine plasma globulin. Steroids 30: 285-293.
cured by la-hydroxyvitamin D3. Med. /. Osaka L7niv. 35: 51. 29. HORST, R. (1984) Recent advances in the quantitation of vitamin
9. SMITH, E. L. & HOLICK,M. F. (1987) The skin: the site of vitamin D and vitamin D metabolite. In: Vitamin D: Basic and Clinical
D3 synthesis and a target tissue for its metabolite 1,25-dihy Aspects, pp. 423-478 (R. Kumar, ed.), Martinus Nijhoff, Boston.
droxyvitamin D3. Steroids 49: 103-131. 30. ADAMS,J. S., CLEMENS, . L. & HOLICK,M. F. (1981) Silica Sep-
T
10. HOLICK, M. F. (1990) Vitamin D and the skin: photobiology, Pak preparative chromatography for vitamin D and its metab
physiology, and therapeutic efficacy for psoriasis. In: Bone and olites. /. Chromatogr. 226: 198-201.
Mineral Research, |N. M. Heersche and J. A. Kanis, eds.), Annual 31. BRUMBAUGH, F., HAUSSLER, H., BURSAC, . M. & HAUSSLER,
P. D. K
Series, Vol. 7, Elsevier, Amsterdam, in press. M. R. (1974) Filter assay for 1,25-dihydroxyvitamin D3. Utili-
6. VITAMIN D ASSAYS 1469
zation of the hormone's target tissue chromatin receptor. Bio (1978) A bioassay capable of measuring 1 picogram of 1,25-
chemistry 13: 4091-4097. dihydroxyvitamin D3. /. Clin. Endocrinol. Metab. 46: 891-896.
32. EISMAN,J. A., HAMSTRA,A. J., KREAM,B. E. & DELucA, H. F. 37. GRAY,R. W., CALDAS,A. E., WILZ, D. R., LEMANN,J. a SMITH,
(1976) A sensitive, precise and convenient method for the de G. A. (1978) Execretion of 3H-1,25-dihydroxyvitamin D3 in
termination of 1,25-dihydroxyvitamin D in human plasma. healthy adults /. Clin. Endocrinol. Metab. 46: 756-765.
Arch. Biochem. Biophys. 176: 235-243. 38. HOLICK,M. F., KRANE,S. M., & POTTS,J.T., JR. (1986) Calcium,
33. REINHARDT,T. A., HORST, R. L., ORF, J. W. & HOLLIS,B. W. phosphorus, and bone metabolism: calcium regulating hor
(1984) A microassay for 1,25-dihydroxyvitamin D not requiring mones. In: Harrison's Principles of Internal Medicine, pp. 1889-
high performance liquid chromatography: application to clinical 1900, (E. Braunwald, K. J. Isselbacher, R. G. Petersdorf, J. D.
studies. /. Clin. Endocrino!. Metab. 58: 91-98. Wilson, J. B. Martin, A. S. Fauci, eds.) 11th ed, McGraw-Hill,
34. HOLLIS,B. W. (1986) Assay of circulating 1,25-dihydroxyvitamin New York.
D involving a novel single-cartridge extraction and purification 39. HOLICK, M. F. (1987) Vitamin D and the kidney. Kidney Int.
procedure. Clin. Chem. 32: 2060-2063. 32:912-929.
35. CHEN, T. C., TURNER,A. K. fin.HOLICK,M. F. (1990) A method 40. HOLICK, M. F., MACLAUGHLIN,J. A. & DOPPELT,S. H. (1981)
for the determination of the circulating concentration of 1,25- Regulation of cutaneous previtamin D3 photosynthesis in man:
dihydroxyvitamin D. /. Nutr. Biochem. (in press). skin pigment is not an essential regulator. Science 211: 590-
36. STERN, P. H., HAMSTRA,A. J., DELUCA, H. F. & BELL,N. H. 593.
Downloaded from jn.nutrition.org by on June 11, 2008