HM Medical Clinic

Take Clomid is contraindicated in the presence of cysts in the ovaries, liver and kidney failure, the presence of pituitary tumors or genital organs clomid dosage The information is provided for informational purposes only and is not a guide for self .

Cialis ne doit pas être prise à tous. Il est important que cialis en ligne est prescrit par un médecin, bien se familiariser avec les antécédents médicaux du patient. Ich habe Probleme mit schnellen Montage. Lesen Sie Testberichte Nahm wie cialis rezeptfrei 30 Minuten vor dem Sex, ohne Erfolg. Beginn der Arbeiten nach 4 Stunden, links ein Freund ein trauriges Ja, und Schwanz in sich selbst nicht ausstehen, wenn es keinen Wunsch ist.

Powerpoint 프레젠테이션

Topical Immunomodulator
Department of Dermatology Seoul National University College of Medicine





Topical Calcineurin Inhibitors Tacrolimus
Protopic: 822 Da 0.1%, 0.03% oint epi-chloro
double bond
double bond
Calcipotriol: 313 Tretinoin: 300 Da) Clinical Efficacy of TCIs: already proven tacrolimus(Protopic), pimecrolimus(Elidel) -used effectively for AD since early 1990s -No need to worry about the side effects of long-term use of topical corticosteroid (esp. useful in sensitive skin areas) -Indications for dermatologic field widened Tacrolimus (Protopic) -extracted from Streptomyces tsukubaensis, a soil microbe found in Tsukuba, Japan -hydrophobic macrolide lactone (MW 822.05 Da) -10-100 times higher immunosuppressive than cyclosporine -initially used for systemic immunosuppression of patients with allograft transplantation


Mechanism of action Inhibition of T cell activation: primary mechanism inhibit calcineurin Absorption properties of tacrolimus MW of 822 Da (cf. CSA 1202 Da), absorbed topically dermal penetration study on intact human skin: 1) relatively low percutaneous absorption 2) average rate of percutaneous penetration from 0.03%, 0.1% and 0.3% tacrolimus ointment: 3.1, 4.9, and 6.8 ng/cm2/hr, respectively 3) higher rates in damaged skin (40 ng/cm2) 4) absorption higher in facial lesions than in lesions on trunk and limbs 5) occlusion did not affect percutaneous penetration • 3-wk course of twice daily application (0.03, 0.1, 0.3%) resulted in blood conc. below 0.25 ng/mL (in renal TPL: 30-60 ng/mL) • The mean time to attain the highest blood conc. is between 5 and 6 h after application in adults and 2.5 h in children. • does not accumulate, either in skin or blood, following repeated application.



Pharmacokinetics – Patients with AD Blood concentration-time profile of Comparison of AUC values in pediatric tacrolimus in adult patients using 0.1% patients administered topical versus systemic tacrolimus ointment with treated body surface area up to 10,000 cm² Cited from T. Ruzicka, and S. Reitamo. Tacrolimus ointment: a topical immunomodulator for AD (eds): Berlin:Springer, 2004.


Effect of tacrolimus ointment on the development of spontaneous dermatitis in NC mice Cited from T. Ruzicka, and S. Reitamo. Tacrolimus ointment: a topical immunomodulator for AD (eds): Berlin:Springer, 2004. • not metabolized in human skin • Systemically available tacrolimus: metabolized by hepatic isoenzyme CYP 3A4 • Since systemic levels of tacrolimus are so low following topical application, interactions with agents which inhibit CYP 3A4 (e.g. erythromycin, itraconazole and ketoconazole) are unlikely. Topical use in AD (early reports): randomized, double-blind vehicle controlled studies No of Pt Treatment >90% improvement in 36.8%(0.1%) 27.5%(0.03%), 6.6%(vehicle) >90% improvement in 40.7%(0.1%) 35.9%(0.03%), 6.9%(vehicle) both group significantly improved 0.03, 0.1, 0.3% decrease in score by 75%(0.3%) for 3 wk 83.3%(0.1%), 66.7%(0.03%), 22.5%(vehi) 0.03, 0.1, 0.3% marked improvement in 86%(0.3%) for 3 wk 100%(0.1%), 0%(0.03%), 0%(vehi) Clinical Experience in Adults Vehicle-controlled 12-week studies: patients achieving at least 90% and at least 50% improvement according to the physician's global evaluation of response Vehicle-controlled 12-week studies: decline in EASI score, change from baseline to end of Tx. Cited from T. Ruzicka, and S. Reitamo. Tacrolimus ointment: a topical immunomodulator for AD (eds): Berlin:Springer, 2004. Clinical Experience in Children Vehicle-controlled multicentre study: physician's global evaluation of improvement at 12 weeks Vehicle-controlled 12-week multicentre study: decline in EASI score, change from baseline to end of treatment Cited from T. Ruzicka, and S. Reitamo. Tacrolimus ointment: a topical immunomodulator for AD (eds): Berlin:Springer, 2004. 1. the most profound difference in symptoms: -achieved within the 1st or 2nd week of Tx -esp. on facial lesions 2. adverse effects: -common (30-50%)--transient skin burning and pruritus -no abnormal changes in laboratory values Tacrolimus (Protopic) -0.03%, 0.1% ointment -Efficacy and safety already reported in the literatures from Japan, Europe, and USA -How about in other Asian countries? So we analyzed the pooled data from 8 Asian countries. Analysis of the pooled data of AD patients from 8 Asian countries vs. Europe, Japan and US (Physician's Global Evaluation of Clinical Response) Malaysia
Thailand
Singapore
Indonesia
Philippines
Success was defined as a rating of better than moderate improvement (≥ 50% improvement)
(Int J Dermatol 2011 in press)

Physician's Global Evaluation of Clinical Response AsiaEurope [1] Reitamo et al. (2002) Japan [3] [4] FK506 Ointment Study Group (1997) [6] Hanifin et al. (2001) Pa
f
t o 40%
Success: defined as a rating of better than moderate
improvement (≥ 50% improvement)
Physician's Global Evaluation of Clinical Response AsiaEurope [2] Reitamo et al. (2002) Japan [5] Otsuki et al. (2003) [8] Paller et al. (2001) Pa
f
t o 40%
Success: defined as a rating of better than moderate
improvement (≥ 50% improvement)

Common Adverse Events Asia 0.1% or 0.03%
Europe 0.1% [1]
Europe 0.03% [1]
US 0.1% [7]
US 0.03% [7]
Asia 0.1% or 0.03%
Europe 0.1% [2]
Europe 0.03% [2]
US 0.1% [8]
US 0.03% [8]
*1Including stinging, pain and soreness. *2Including itch and worsening of pruritus.
[1] Reitamo et al. (2002) [2] Reitamo et al. (2002) [7] Soter et al. (2001) [8] Paller et al. (2001) Conclusion about the efficacy and safety Of tacrolimus ointment in Asian Study (Int J Dermatol 2011 in press)  effective and well tolerated treatment option in patients with AD in Asia. * The efficacy and safety of tacrolimus are similar to those in the US, European and Japan studies. New paradigm for use: Proactive treatment of AD with tacrolimus ointment 2 or 3 times application of tacrolimus oint to normal-appearing skin reduces time to relapse -Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment. Allergy 2008: 63: 742–750 -Three Times Weekly Tacrolimus Ointment Reduces Relapse in Stabilized Atopic Dermatitis: A New Paradigm for Use. Pediatrics 2008;122;e1210-e121 a. Flare prevention with tacrolimus ointment, continue with maintenance therapy (1–2 times/week) b. Treatment of flares with topical corticosteroids Cited from T. Ruzicka, and S. Reitamo. Tacrolimus ointment: a topical immunomodulator for AD (eds): Berlin:Springer, 2004. Pimecrolimus (Elidel) derivative of ascomycin (discovered in a screen for antifungal agents from Streptomyces hygroscopicus var. ascomyceticus) pharmacokinetic study -1% pimecrolimus cream was applied to 15-59% of total body surface in 12 adult patients---majority of blood samples provided nonquantifiable conc. -in 58 pediatric patient treated on up to 92% of total body surface area, blood conc were consistently low. -no skin atrophy -no evidence of systemic accumulation with repeated dosing Pimecrolimus (Elidel) Clinical Efficacy -Study subjects: mild to moderate AD patients In infants Elidel clears AD signs Elidel, n=123
Vehicle, n=63

*** P< 0.001 1Investigators' Global Assessment (IGA) of 0 (clear) or 1 (almost clear) In infants, Elidel clears AD signs Baseline
12-month old female patient with moderate atopic eczema at baseline
Clinical photographs courtesy of Prof. R. Kaufmann, Frankfurt, Germany
In children, Elidel clears AD signs Elidel, n=267
Vehicle, n=136

* P 0.05 ** P 0.01 *** P 0.001 1Investigators' Global Assessment (IGA) of 0 (clear) or 1 (almost clear) In children, Elidel clears AD signs 4-year old male patient with moderate atopic eczema at baseline Clinical photographs courtesy of Dr D. Pariser, Norfolk, VA, USA In children, Elidel particularly effective in face and neck area Vehicle face/neck Progressive improvement in total body IGA rating in pediatric and adult patients Lü bbe J et al. Poster presented at EADV 2003, Barcelona
Progressive improvement in facial IGA rating in pediatric and adult patients -common (10%)--transient skin burning and pruritus -no abnormal changes in laboratory values Naturalistic, open-label, multicenter study of long-term management in patients ≥ 3 mo of age with mild or moderate AD using Elidel (pimecrolimus) cream 1% 3 Months - Main Analysis of Global ELIDEL bid, on an "as needed" basis (initiating treatment at first signs and symptoms of AD) variable treatment period and study duration: 3 months core phase followed by a flexible duration of up to 9 months Patients enrolled / Country • Region Europe: • Region LatAm: • Region Asia Pacific: LatAm total: 345 Treatment Success (IGA  1) ITT (n = 2014), LOCF Treatment Success (IGA  1) AP Regional DATA ITT (n = 324), LOCF Conclusions of NOVIDEL study • effective and sustained disease control with ELIDEL in AP regions as well as in Western contries especially effective; for children on the face • excellent safety profile and tolerability • high patient acceptance Pimecrolimus vs tacrolimus 1. Direct comparison of efficacy--difficult -pimecrolimus treated for mild to mod AD -tacrolimus treated for mod to severe AD 2. Direct comparison of local adverse effects pimecrolimus (10%) < tacrolimus (50%) 3. Pimecrolimus is more lipophilic -higher affinity to the skin -less permeation through the skin 4. Tacrolimus: ca 3-fold higher affinity to FKBP than pimecrolimus and consequently a higher calcineurin- inhibiting potency Skin penetration and permeation: pimecrolimus and tacrolimus are different Penetration into skin1 Permeation through skin1 1Human skin in vitro Experiences in SNUH tacrolimus 0.1% ointment 치료 효과 tacrolimus 0.03% ointment 치료 효과 0.03% tacrolimus 치료 전 0.03% tacrolimus 치료 2주 1% Elidel cream 치료 효과 1% Elidel 치료 효과 Calcineurin Inhibitors vs Corticosteroids Cytokines Mediators Systemic exposure Protopic (tacrolimus) Pharmacokinetics of 0.1% Tacrolimus Ointment After First and Repeated Application to Adults or children with Moderate to Severe AD (J Invest Dermatol 2005;125:68 –71) (J Invest Dermatol 2005;124:695 –699) Comparative absorption of tacrolimus: 0.1% tacrolimus oint vs. adult or childhood transplanted patients administered tacrolimus systemically. Mean maximum blood tacrolimus concentrations in adults and children receiving tacrolimus 0.1% oint, stratified by BSA affected. Br J Dermatol 2007: 157:861–73 Elidel (pimecrolimus) Minimal Increase in Blood Concentrations with Rising % BSA Treated BSA affected on Day 1 (%)
Difference in mean blood concentration for infants with 90% BSA and 10% BSA is 0.4 ng/ml Lakhanpaul et al. World Kongr. Ped. Derm. 2001 Pharmacokinetics of TCIs in adult AD: A randomized, investigator-blind comparison: x2/d Tx for 13 d, pimecrolimus cream 1% and tacrolimus ointment 0.1% (JAAD2005;53:602-9) ELIDEL does not deplete skin Langerhans' cells, in contrast to corticosteroids Number of Ia+ dendritic cells in
murine epidermal sheets after
5 days of topical treatment

Controlsa
Clobetasol
Betamethasone Hydrocortisone
aTreatment with solvent alone
Meingassner JG et al. Br J Dermatol 2003;149:853–7
long-term safety of TCIs 1) Minimal systemic absorption 2) Thousands of patients in many clinical trials with a very impressive safety record 3) No effect on collagen synthesis: no skin atrophy 4) No increased risk of cutaneous infection in AD 5) No decrease in immunocompetence in the skin 6) No clinical evidence of increased risk of malignancy both in adults or children FDA: updated labeling for Elidel Cream and Protopic Ointment in 2006 Long-term safety of topical calcineurin inhibitors has
not been established

Therefore:
Continuous long-term use of TCIs, including Elidel Cream, and Protopic
Ointment in any age group should be avoided, and application limited to
areas of involvement with AD.
Elidel Cream is not indicated for use in children less than 2 years of age.
Protopic Ointment is not indicated for use in children less than 2 years of
age. Only 0.03% Protopic Ointment is indicated for use in children 2-15
years of age.
Is there clinical evidence for an increased risk of malignancies? Carcinogenicity Studies with Pimecrolimus and Tacrolimus
MRHD: maximally recommended human dose NOAEL: non-observed adverse event level LOAEL: lowest observed adverse event levels (Dermatology 2005;211:174–87) Reports of Malignancies
in Comparative Clinical Trials*
(Worldwide Data as of December 2005)
23 Comparative Clinical Trials
(N 7000)
Tacrolimus ointment
(N 500)
(N 4200)
(N 900)
(N 1400)
Squamous
Basal Cell
Male, 75 yr
Male, 69 yr
Giant Cell
Lymphoma
Male, 26 yr
*Study duration (range: 3 weeks to 7 months) was comparable for all treatment groups Carroll CL, Fleischer AB Jr. Drugs Today. 2006;7:431-439. Clinical data show no evidence for an increased risk of malignancies with Protopic or Elidel insufficient evidence in the epidemiologic literature to infer whether TCIs do or do not cause malignancy. (Br J Dermatol. 2011 Apr 5. doi: 10.1111/j.1365-2133) Conclusions about TCI in AD 1. Very effective Especially useful in sensitive skin area such as face 2. Excellent safety profile and tolerability 1) no concerns associated with long-term use of TCS 2) no evidence for an increased risk of malignancies 3. Proactive treatment suggested

Source: http://www.allergy.or.kr/journal/abst/2011s/030_ppt.pdf

Microsoft word - e-fps-1p _gb_.doc

Enzymatic Immunoassay for the quantitative determination of free Prostata Specific Antigen (PSA) in human serum The standards are calibrated against NIBSC (WHO) Prostate cancer is the most frequent type of cancer found in the man and the second cause of death due to the cancer in man, Until recently, digital rectal examination was the most accepted Zero Standard/Diluent:

The world anti-doping code

The World Anti-Doping Code JU-JITSU FEDERATION Anti-Doping Rules Version 2.0 (Based upon the 2009 revised Code) December 2008 TABLE OF CONTENTS Fundamental Rationale for the Code and JJIF's Anti-Doping Rules . 3 Scope . 3 DEFINITION OF DOPING . 4 ANTI-DOPING RULE VIOLATIONS . 4