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Geetha.T Int. Journal of Engineering Research and Applications www.ijera.com
ISSN : 2248-9622, Vol. 4, Issue 12( Part 4), December 2014, pp.35-38
www.ijera.com 35 | P a g e
Survival function Of Realization process for Hemodynamic and
hormonal effects of human GH in healthy volunteers
Geetha.T* and Anandhi.N**.
* Asst.Professor of Mathematics .K. N. Govt. Arts College for Women. Thanjavur. Tamilnadu. South India
**Research Scholar ,PG & Research Department of Mathematics. K. N. Govt. Arts College for Women.
Thanjavur. Tamilnadu. South India
Abstract
Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. To investigate hemodynamic and
hormonal effects of ghrelin, a novel growth hormone (GH)-releasing peptide, we gave six healthy men an
intravenous bolus of human ghrelin or placebo and vice versa 1–2 wk apart in a randomized fashion. Ghrelin
elicited a marked increase in circulating GH. The elevation of GH lasted longer than 60 min after the bolus
injection. Injection of ghrelin significantly decreased mean arterial pressure without a significant change in heart
rate .In summary, human ghrelin elicited a potent, long lasting GH release and had beneficial hemodynamic
effects via reducing cardiac after load and increasing cardiac output without an increase in heart rate. Thus, the
purpose of this study was to investigate hemodynamic and hormonal effects of intravenous ghrelin in healthy
volunteers. This paper discussed the constant stress level of healthy volunteers with times to damage of stress
effect and recoveries
keywords: hemodynamics; hormones; vasodilation
I. Introduction
Intravenous injection of ghrelin elicited a potent,
long-lasting GH release in healthy volunteers and
ghrelin decreased mean arterial pressure and
increased cardiac output but did not increase heart
rate. We studied six healthy male hospital staff
members, aged 30 -61 yr, who weighed 68- 65 kg.
None of them had any history of cardiovascular,
renal, respiratory, hepatic, or metabolic disease, and
none were taking any drugs. Physical examination
and lector cardio graphic and echo cardio graphic
findings were also normal. The study was approved
by the ethics committee of the National
Cardiovascular Center, and all subjects gave written
informed consent. Human ghrelin was obtained from
the Peptide Institute, Osaka, Japan. The homogeneity
of human ghrelin was confirmed by reverse phase,
high-performance liquid chromatography (RP-HPLC)
and amino acid analysis. Ghrelin was dissolved in
distilled water with 4% D-mannitol and was sterilized
by passage through a 0.22-mm filter (Millipore).
Ghrelin was stored as 1 ml volumes (each containing
600 mg ghrelin) at 280°C until the time of
preparation for administration.
The subjects were studied on 2 separate days (1
day, ghrelin; 1 day, placebo) 1–2 wk apart in a
randomized, crossover fashion. This study was
performed after the subjects fasted overnight, because
plasma ghrelin level has been shown to be altered by
food intake was positioned in the pulmonary artery
through a jugular vein to measure pulmonary arterial
pressure and pulmonary capillary wedge pressure.
Cardiac output was determined by thermo dilution
method in triplicate [1,2]. A 22-gauge cannula was
inserted into a radial artery for measurement of heart
rate and systemic arterial pressure. Another 22-gauge
cannula was inserted into a forearm vein for infusion
of ghrelin. Ghrelin (10 mg/kg) was dissolved in 5 ml
saline. After an equilibration period of 60 min,
baseline measurements were performed[3]. Then, 5
ml of ghrelin solution or placebo (0.9% saline) was
administered as an intravenous bolus. Hemodynamic
measurements were repeatedly performed until 120
min after the injection
REVIEW ARTICLE OPEN ACCESS
Geetha.T Int. Journal of Engineering Research and Applications www.ijera.com
ISSN : 2248-9622, Vol. 4, Issue 12( Part 4), December 2014, pp.35-38
www.ijera.com 36 | P a g e
Fig. Circulating ghrelin level after a single injection of ghrelin (A). Effects of ghrelin on circulating growth
hormone (GH) (B). Data are means 6 SE. *P , 0.05 vs. placebo group. The
arrow indicates an intravenous injection of ghrelin or placebo.
Mathematical Model
Notations
nT - The time interval between two consecutive stress effects.
nC - The magnitude of GH secretion due to nth
stress.
 

n
i
i tTntN
1
},0max{)( be the number of stimuli.
Z - A known threshold or pre specified value of GH secretion
Realization of the process
Here the damage is allowed to decrease between successive stimuli.
That is, „recovery‟ takes place in some deterministic fashion
},0),({  ttZZ Such that 0)0( Z and 0)( tZ for all 0t with probability 1.
xT = inf })(;0{ xtZt  is first passage time[4,5]. )(tF Bounds of survival function.
The survival function of xT is
,
)1(
1
!
)(
)(
]/[1
0
k
t
k
k
t
t
k
k
t
etF 




 






0t …(1)
When t is large the numerical computation of (1) can be radius, because for large ,t the number of
terms in the sum is large. Derived the following bounds of )(tF ,
,0)()()/1( )()(
 
ttHeetFee ataata
where sa  and s is the largest
real root of s  )(s
e here .1and1  For fixed 0t , )(tF 0,)]([ 0 ttF k
and
,...3,2,1,0,)1( 00  ktktkt
Geetha.T Int. Journal of Engineering Research and Applications www.ijera.com
ISSN : 2248-9622, Vol. 4, Issue 12( Part 4), December 2014, pp.35-38
www.ijera.com 37 | P a g e
Therefore, upper bound of )(tF is:
[min)( tF H [),(t ])]( 0
k
tF
When t is large enough, then
kata
tFee )]([ 0
)(

The data is fitted with the distribution and the corresponding values for case:1 and case:2 are obtained
as follows
Case α  t )(tF
Gherlin 0.0344 0.01 3
1
2
3
4
0.999993
0.999985
0.999972
0.999954
GH 0.0464 0.0114
1
2
3
4
0.999992
0.999984
0.999975
0.999961
0
0.5
1
1.5
2
2.5
3
3.5
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
PlasmaGherlinLevel
Time
Placebo
Ghrelin
Geetha.T Int. Journal of Engineering Research and Applications www.ijera.com
ISSN : 2248-9622, Vol. 4, Issue 12( Part 4), December 2014, pp.35-38
www.ijera.com 38 | P a g e
II. Conclusion:
In the paper we found the constant stress level of healthy volunteers with times to damage of stress effect
and recoveries for hemodynamic and hormonal effects of ghrelin, a novel growth hormone (GH)-releasing
peptide.
References
[1.] G Amato , C Carella ,S Fazio , G La Montagna ,A Cittadini , D Sabatini ,C arciano- Mone, L
Sacca , and A Bellastella . Body composition, bone metabolism, heart tructure and function in growth
hormone deficient adults before and after growth hormone replacement therapy at low doses. J Clin
Endocrinol Metab 77: 1671–1676, 1993
[2.] G Bisi ,V Podio , M R Valetto , F Broglio ,G Bertuccio ,G Del Rio ,E Arvat ,MF Boghen , R
Deghenghi , G Muccioli ,H Ong , and E Ghigo . Acute cardiovascular and hormonal effects of GH
and hexarelin, a synthetic GH-releasing peptide, in humans. J Endocrinol Invest22: 266–272, 1999
[3.] RH Boger, CS kamira , SM Bode-Boger, G Brabant , A Muhlen , and J Frolich . Nitric oxide may
mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth
hormone deficiency: a double-blind, placebo-controlled study. J Clin Invest 98: 2706–2713, 1996
[4.] Hanagal, D.D., “Testing reliability in a bivariate exponential stress-strength model.” J. Indian Stat.
Assoc., 33 (1995), 41
[5.] Hameed, M.S.A. and Proschan, F., “Shock models with underlying birth process.” J. Appl. Proba.,
12 (1975), 18-28.
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
1 2 3 4 5 6 7 8 9 10 11 12 13
SerumGHLevel
Time
Placebo
Ghrelin

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Survival function Of Realization process for Hemodynamic and hormonal effects of human GH in healthy volunteers

  • 1. Geetha.T Int. Journal of Engineering Research and Applications www.ijera.com ISSN : 2248-9622, Vol. 4, Issue 12( Part 4), December 2014, pp.35-38 www.ijera.com 35 | P a g e Survival function Of Realization process for Hemodynamic and hormonal effects of human GH in healthy volunteers Geetha.T* and Anandhi.N**. * Asst.Professor of Mathematics .K. N. Govt. Arts College for Women. Thanjavur. Tamilnadu. South India **Research Scholar ,PG & Research Department of Mathematics. K. N. Govt. Arts College for Women. Thanjavur. Tamilnadu. South India Abstract Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. To investigate hemodynamic and hormonal effects of ghrelin, a novel growth hormone (GH)-releasing peptide, we gave six healthy men an intravenous bolus of human ghrelin or placebo and vice versa 1–2 wk apart in a randomized fashion. Ghrelin elicited a marked increase in circulating GH. The elevation of GH lasted longer than 60 min after the bolus injection. Injection of ghrelin significantly decreased mean arterial pressure without a significant change in heart rate .In summary, human ghrelin elicited a potent, long lasting GH release and had beneficial hemodynamic effects via reducing cardiac after load and increasing cardiac output without an increase in heart rate. Thus, the purpose of this study was to investigate hemodynamic and hormonal effects of intravenous ghrelin in healthy volunteers. This paper discussed the constant stress level of healthy volunteers with times to damage of stress effect and recoveries keywords: hemodynamics; hormones; vasodilation I. Introduction Intravenous injection of ghrelin elicited a potent, long-lasting GH release in healthy volunteers and ghrelin decreased mean arterial pressure and increased cardiac output but did not increase heart rate. We studied six healthy male hospital staff members, aged 30 -61 yr, who weighed 68- 65 kg. None of them had any history of cardiovascular, renal, respiratory, hepatic, or metabolic disease, and none were taking any drugs. Physical examination and lector cardio graphic and echo cardio graphic findings were also normal. The study was approved by the ethics committee of the National Cardiovascular Center, and all subjects gave written informed consent. Human ghrelin was obtained from the Peptide Institute, Osaka, Japan. The homogeneity of human ghrelin was confirmed by reverse phase, high-performance liquid chromatography (RP-HPLC) and amino acid analysis. Ghrelin was dissolved in distilled water with 4% D-mannitol and was sterilized by passage through a 0.22-mm filter (Millipore). Ghrelin was stored as 1 ml volumes (each containing 600 mg ghrelin) at 280°C until the time of preparation for administration. The subjects were studied on 2 separate days (1 day, ghrelin; 1 day, placebo) 1–2 wk apart in a randomized, crossover fashion. This study was performed after the subjects fasted overnight, because plasma ghrelin level has been shown to be altered by food intake was positioned in the pulmonary artery through a jugular vein to measure pulmonary arterial pressure and pulmonary capillary wedge pressure. Cardiac output was determined by thermo dilution method in triplicate [1,2]. A 22-gauge cannula was inserted into a radial artery for measurement of heart rate and systemic arterial pressure. Another 22-gauge cannula was inserted into a forearm vein for infusion of ghrelin. Ghrelin (10 mg/kg) was dissolved in 5 ml saline. After an equilibration period of 60 min, baseline measurements were performed[3]. Then, 5 ml of ghrelin solution or placebo (0.9% saline) was administered as an intravenous bolus. Hemodynamic measurements were repeatedly performed until 120 min after the injection REVIEW ARTICLE OPEN ACCESS
  • 2. Geetha.T Int. Journal of Engineering Research and Applications www.ijera.com ISSN : 2248-9622, Vol. 4, Issue 12( Part 4), December 2014, pp.35-38 www.ijera.com 36 | P a g e Fig. Circulating ghrelin level after a single injection of ghrelin (A). Effects of ghrelin on circulating growth hormone (GH) (B). Data are means 6 SE. *P , 0.05 vs. placebo group. The arrow indicates an intravenous injection of ghrelin or placebo. Mathematical Model Notations nT - The time interval between two consecutive stress effects. nC - The magnitude of GH secretion due to nth stress.    n i i tTntN 1 },0max{)( be the number of stimuli. Z - A known threshold or pre specified value of GH secretion Realization of the process Here the damage is allowed to decrease between successive stimuli. That is, „recovery‟ takes place in some deterministic fashion },0),({  ttZZ Such that 0)0( Z and 0)( tZ for all 0t with probability 1. xT = inf })(;0{ xtZt  is first passage time[4,5]. )(tF Bounds of survival function. The survival function of xT is , )1( 1 ! )( )( ]/[1 0 k t k k t t k k t etF              0t …(1) When t is large the numerical computation of (1) can be radius, because for large ,t the number of terms in the sum is large. Derived the following bounds of )(tF , ,0)()()/1( )()(   ttHeetFee ataata where sa  and s is the largest real root of s  )(s e here .1and1  For fixed 0t , )(tF 0,)]([ 0 ttF k and ,...3,2,1,0,)1( 00  ktktkt
  • 3. Geetha.T Int. Journal of Engineering Research and Applications www.ijera.com ISSN : 2248-9622, Vol. 4, Issue 12( Part 4), December 2014, pp.35-38 www.ijera.com 37 | P a g e Therefore, upper bound of )(tF is: [min)( tF H [),(t ])]( 0 k tF When t is large enough, then kata tFee )]([ 0 )(  The data is fitted with the distribution and the corresponding values for case:1 and case:2 are obtained as follows Case α  t )(tF Gherlin 0.0344 0.01 3 1 2 3 4 0.999993 0.999985 0.999972 0.999954 GH 0.0464 0.0114 1 2 3 4 0.999992 0.999984 0.999975 0.999961 0 0.5 1 1.5 2 2.5 3 3.5 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 PlasmaGherlinLevel Time Placebo Ghrelin
  • 4. Geetha.T Int. Journal of Engineering Research and Applications www.ijera.com ISSN : 2248-9622, Vol. 4, Issue 12( Part 4), December 2014, pp.35-38 www.ijera.com 38 | P a g e II. Conclusion: In the paper we found the constant stress level of healthy volunteers with times to damage of stress effect and recoveries for hemodynamic and hormonal effects of ghrelin, a novel growth hormone (GH)-releasing peptide. References [1.] G Amato , C Carella ,S Fazio , G La Montagna ,A Cittadini , D Sabatini ,C arciano- Mone, L Sacca , and A Bellastella . Body composition, bone metabolism, heart tructure and function in growth hormone deficient adults before and after growth hormone replacement therapy at low doses. J Clin Endocrinol Metab 77: 1671–1676, 1993 [2.] G Bisi ,V Podio , M R Valetto , F Broglio ,G Bertuccio ,G Del Rio ,E Arvat ,MF Boghen , R Deghenghi , G Muccioli ,H Ong , and E Ghigo . Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans. J Endocrinol Invest22: 266–272, 1999 [3.] RH Boger, CS kamira , SM Bode-Boger, G Brabant , A Muhlen , and J Frolich . Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency: a double-blind, placebo-controlled study. J Clin Invest 98: 2706–2713, 1996 [4.] Hanagal, D.D., “Testing reliability in a bivariate exponential stress-strength model.” J. Indian Stat. Assoc., 33 (1995), 41 [5.] Hameed, M.S.A. and Proschan, F., “Shock models with underlying birth process.” J. Appl. Proba., 12 (1975), 18-28. 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 1 2 3 4 5 6 7 8 9 10 11 12 13 SerumGHLevel Time Placebo Ghrelin