• 제목/요약/키워드: Gupta

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Exploring the Potential of Natural Products as FoxO1 Inhibitors: an In Silico Approach

  • Anugya Gupta;Rajesh Haldhar;Vipul Agarwal;Dharmendra Singh Rajput;Kyung-Soo Chun;Sang Beom Han;Vinit Raj;Sangkil Lee
    • Biomolecules & Therapeutics
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    • 제32권3호
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    • pp.390-398
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    • 2024
  • FoxO1, a member of the Forkhead transcription factor family subgroup O (FoxO), is expressed in a range of cell types and is crucial for various pathophysiological processes, such as apoptosis and inflammation. While FoxO1's roles in multiple diseases have been recognized, the target has remained largely unexplored due to the absence of cost-effective and efficient inhibitors. Therefore, there is a need for natural FoxO1 inhibitors with minimal adverse effects. In this study, docking, MMGBSA, and ADMET analyses were performed to identify natural compounds that exhibit strong binding affinity to FoxO1. The top candidates were then subjected to molecular dynamics (MD) simulations. A natural product library was screened for interaction with FoxO1 (PDB ID-3CO6) using the Glide module of the Schrödinger suite. In silico ADMET profiling was conducted using SwissADME and pkCSM web servers. Binding free energies of the selected compounds were assessed with the Prime-MMGBSA module, while the dynamics of the top hits were analyzed using the Desmond module of the Schrödinger suite. Several natural products demonstrated high docking scores with FoxO1, indicating their potential as FoxO1 inhibitors. Specifically, the docking scores of neochlorogenic acid and fraxin were both below -6.0. These compounds also exhibit favorable drug-like properties, and a 25 ns MD study revealed a stable interaction between fraxin and FoxO1. Our findings highlight the potential of various natural products, particularly fraxin, as effective FoxO1 inhibitors with strong binding affinity, dynamic stability, and suitable ADMET profiles.

Use of caudal pancreatectomy as a novel adjunct procedure to proximal splenorenal shunt in patients with noncirrhotic portal hypertension: A retrospective cohort study

  • Shahana Gupta;Biju Pottakkat;Raja Kalayarasan;Gnanasekaran Senthil;Pagadala Naga Balaji Nitesh
    • 한국간담췌외과학회지
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    • 제26권2호
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    • pp.178-183
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    • 2022
  • Backgrounds/Aims: Proximal splenorenal shunt (PSRS) is considered a one-time treatment for noncirrhotic portal hypertension (NCPH) to prevent recurrent upper gastrointestinal (UGI) hemorrhage and long-term complications. Long-term shunt patency is necessary to achieve these. The lie of the shunt is a contributing factor to early shunt thrombosis. We investigated the role of resection of the distal tail of pancreas (caudal pancreatectomy [CP]) in improving the lie of shunt and decreasing shunt thrombosis. Methods: This was a retrospective cohort study of patients with NCPH who underwent PSRS between 2014-2020 in JIPMER, Puducherry, India. CP was performed in patients with a long tail of pancreas, with the tip of pancreatic tail extending up to splenic hilum on preoperative CT. Perioperative parameters and shunt patency rate of patients who underwent PSRS with CP (Group A) were compared with patients undergoing conventional PSRS (Group B). Statistical analysis was performed using the Mann-Whitney U test and χ2 test. Results: Eighty four patients with NCPH underwent PSRS (extrahepatic portal vein obstruction = 39; noncirrhotic portal fibrosis = 45). Blood loss was lower (p = 0.002) and post-shunt fall in portal pressure higher (p = 0.002) in Group A. Shunt thrombosis rate was lower (p = 0.04) while rate of complete variceal regression (p = 0.03) and biochemical pancreatic leak (p = 0.01) were higher in Group A.There was no clinically relevant pancreatic fistula in either group. Conclusions: CP is a safe and useful technique for reducing shunt thrombosis after PSRS in patients with NCPH by improving the lie of shunt.

Three-dimensional computer navigation in the reconstruction of complex unilateral orbital fractures: evaluation and review of applications

  • Parampreet Singh Saini;Rajesh Kumar;Manu Saini;Tarush Gupta;Sunil Gaba;Ramesh Kumar Sharma
    • 대한두개안면성형외과학회지
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    • 제25권4호
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    • pp.161-170
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    • 2024
  • Background: The eyes are the central aesthetic unit of the face. Maxillofacial trauma can alter facial proportions and affect visual function with varying degrees of severity. Conventional approaches to reconstruction have numerous limitations, making the process challenging. The primary objective of this study was to evaluate the application of three-dimensional (3D) navigation in complex unilateral orbital reconstruction. Methods: A prospective cohort study was conducted over 19 months (January 2020 to July 2021), with consecutive enrollment of 12 patients who met the inclusion criteria. Each patient was followed for a minimum period of 6 months. The principal investigator carried out a comparative analysis of several factors, including fracture morphology, orbital volume, globe projection, diplopia, facial morphic changes, lid retraction, and infraorbital nerve hypoesthesia. Results: Nine patients had impure orbital fractures, while the remainder had pure fractures. The median orbital volume on the normal side (30.12 cm3; interquartile range [IQR], 28.45-30.64) was comparable to that of the reconstructed orbit (29.67 cm3; IQR, 27.92-31.52). Diplopia improved significantly (T(10)= 2.667, p= 0.02), although there was no statistically significant improvement in globe projection. Gross symmetry of facial landmarks was achieved, with comparable facial width-to-height ratio and palpebral fissure lengths. Two patients reported infraorbital hypoesthesia at presentation, which persisted at the 6-month follow-up. Additionally, five patients developed lower lid retraction (1-2 mm), and one experienced implant impingement at the infraorbital border. Conclusion: Our study provides level II evidence supporting the use of 3D navigation to improve surgical outcomes in complex orbital reconstruction.

6세기 푸난 목조불상에 대한 시론(試論) (A Preliminary research on Sixth-century Wooden Buddha Images from Funan)

  • 노남희
    • 미술자료
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    • 제99권
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    • pp.10-29
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    • 2021
  • 본 논문은 지금의 베트남 남부 메콩강 삼각주 지역에서 출토된 목조불상에 대한 시론적인 연구이다. 지금까지 알려진 바에 의하면 메콩강 삼각주 지역에서는 약 서른여 점의 목조불상이 출토되었다. 이들은 옥 에오(Oc Eo) 등 동남아 최초의 국가였던 푸난(Funan)의 주요 유적지에서 발견되었고, 대개 6세기 무렵으로 추측되므로 푸난의 불상으로 간주할 수 있다. 이 불상들은 석조불상과 함께 동남아 초기 불상의 양상을 보여준다는 점에서 중요한 자료이다. 푸난 목조불상은 방사성탄소연대측정법과 양식적 특징을 종합하면 대부분 6세기 무렵에 만들어진 것으로 보인다. 현재까지 공개된 푸난 목조불상 가운데 형상을 비교적 확실히 알아볼 수 있는 8점에 대해 도상과 양식을 분석하였는데, 이들은 자세와 착의법, 수인에 따라 네 가지 유형으로 구분할 수 있었다. 세장한 신체와 몸에 달라붙는 대의의 표현은 기본적으로 인도 굽타시대 사르나트 불상 양식을 공통적으로 따르고 있었으나, 유형에 따라서는 직립한 자세와 편단우견형의 착의법, 스리랑카 불상에서 주로 보이는 설법인(vitarka mudra)을 보이는 등, 남인도 불상 양식도 발견할 수 있었다. 이는 푸난의 불교조각가들이 인도의 주요 불상 양식을 적절히 섞어 새로운 불상 양식을 창안했음을 알려준다. 이와 함께 주목되는 것은 푸난 목조불상의 출토 현황이다. 같은 유적에서 발견된 비슷한 시기의 힌두신상은 나무로 만들어진 예를 찾아볼 수 없는 데 반해, 불상만은 유독 나무로 많이 만들어진 현상에 대하여 불상과 나무라는 재질 사이에는 단순한 제작상의 이유가 아닌 보다 밀접한 관계가 있을 수 있음을 상정해 보았다. 불교 문헌상 전해지는 최초의 불상은 바로 전단목이라는 나무로 만들어진 '우전왕상'이다. 우전왕상은 비슷한 시기인 6세기 무렵 중국 남조에도 알려져 있었는데, 흥미롭게도 남조에는 푸난에서 가져왔다는 '전단서상'이 있었다고 전한다. 이는 우전왕상에 대한 이야기가 푸난에도 공유되어 있었을 가능성을 시사하며, 나아가 푸난에서 나무로 불상을 다수 제작하게 된 주요 동인으로 작용했을 가능성이 있다.

6-7세기의 동남아 힌두 미술 - 인도 힌두미술의 전파와 초기의 변용 - (Southeast Asian Hindu Art from the 6th to the 7th Centuries)

  • 강희정
    • 동남아시아연구
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    • 제20권3호
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    • pp.263-297
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    • 2010
  • The relics of the Southeast Asian civilizations in the first phase are found with the relics from India, China, and even further West of Persia and Rome. These relics are the historic marks of the ancient interactions of various continents, mainly through the maritime trade. The traces of the indic culture, which appears in the historic age, are represented in the textual records and arts, regarded as the essence of the India itself. The ancient Hindu arts found in various locations of Southeast Asia were thought to be transplanted directly from India. However, Neither did the Gupta Hindu Art of India form the mainstream of the Gupta Art, nor did it play an influential role in the adjacent areas. The Indian culture was transmitted to Southeast Asia rather intermittently than consistently. If we thoroughly compare the early Hindu art of India and that of Southeast Asia, we can find that the latter was influenced by the former, but still sustained Southeast Asian originality. The reason that the earliest Southeast Asian Hindu art is discovered mostly in continental Southeast Asia is resulted from the fact that the earliest networks between India and the region were constructed in this region. Among the images of Hindu gods produced before the 7th century are Shiva, Vishnu, Harihara, and Skanda(the son of Shiva), and Ganesha(the god of wealth). The earliest example of Vishnu was sculpted according to the Kushan style. After that, most of the sculptures came to have robust figures and graceful proportions. There are a small number of images of Ganesha and Skanda. These images strictly follow the iconography of the Indian sculpture. This shows that Southeast Asians chose their own Hindu gods from the Hindu pantheon selectively and devoted their faiths to them. Their basic iconography obediently followed the Indian model, but they tried to transform parts of the images within the Southeast Asian contexts. However, it is very difficult to understand the process of the development of the Hindu faith and its contents in the ancient Southeast Asia. It is because there are very few undamaged Hindu temples left in Southeast Asia. It is also difficult to make sure that the Hindu religion of India, which was based on the complex rituals and the caste system, was transplanted to Southeast Asia, because there were no such strong basis of social structure and religion in the region. "Indianization" is an organized expansion of the Indian culture based on the sense of belonging to an Indian context. This can be defined through the process of transmission and progress of the Hindu or Buddhist religions, legends about purana, and the influx of various epic expression and its development. Such conditions are represented through the Sanskrit language and the art. It is the element of the Indian culture to fabricate an image of god as a devotional object. However, if we look into details of the iconography, style, and religious culture, these can be understood as a "selective reception of foreign religious culture." There were no sophisticated social structure yet to support the Indian culture to continue in Southeast Asia around the 7th century. Whether this phenomena was an "Indianization" or the "influx of elements of Indian culture," it was closely related to the matter of 'localization.' The regional character of each local region in Southeast Asia is partially shown after the 8th century. However it is not clear whether this culture was settled in each region as its dominant culture. The localization of the Indian culture in Southeast Asia which acted as a network connecting ports or cities was a part of the process of localization of Indian culture in pan-Southeast Asian region, and the process of the building of the basis for establishing an identity for each Southeast Asian region.

airGRdatassim을 이용한 앙상블 기반 수문자료동화 기법의 비교 및 불확실성 평가 (Comparative assessment and uncertainty analysis of ensemble-based hydrologic data assimilation using airGRdatassim)

  • 이가림;이송희;김보미;우동국;노성진
    • 한국수자원학회논문집
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    • 제55권10호
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    • pp.761-774
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    • 2022
  • 가뭄과 홍수의 예측, 기후변화가 유역 유출량, 더 나아가 수질 및 생태계에 미치는 영향의 정확한 분석을 위해서는 수문 모의 과정의 불확실성을 정량화하고 최소화하기 위한 노력이 필요하다. 수문자료동화는 수문모형의 상태량이나 매개변수를 갱신(update)하여 모의 초기 조건의 가장 가능성 있는 추정치를 생성하는 기법으로, 실시간 관측 정보를 이용하여 예측 정확도를 향상시킬 수 있는 방법이다. 본 연구에서는 airGRdatassim 모형을 이용하여 앙상블 기반 순차 자료동화 기법인 앙상블 칼만 필터와 파티클 필터로 용담댐 유역에 대해 일 유출을 모의하고, 자료동화 기법별 특성을 비교 및 분석하였다. 모의 결과, Kling-Gupta efficiency (KGE) 지표가 자료동화 적용 전 0.799에서 앙상블 칼만 필터와 파티클 필터 적용시 각각 0.826, 0.933으로 향상되었다. 또한 기상 강제력 노이즈의 범위, 갱신 대상 상태량 설정, 앙상블 수 등 수문자료동화의 설정과 관련된 하이퍼-매개변수(hyper-parameter)의 불확실성이 모의 예측 성능에 미치는 영향을 분석하였다. 강수 및 잠재 증발산 강제력의 오차 범위에 대한 민감도 분석 결과, 모든 모의 범위에서 파티클 필터가 앙상블 칼만 필터보다 예측 성능이 우수하였다. 파티클 필터는 기상 강제력 오차 크기가 작을수록 모의 성능이 향상되었으며, 앙상블 칼만 필터는 상대적으로 오차가 큰 경우 최적 성능이 확인되었다. 한편, 자료동화시 갱신되는 상태량의 종류를 줄일수록 자료동화에 의한 모의 성능은 감소하였다. 본 연구의 모의 실험 결과는 앙상블 자료동화를 이용하여 일 유출 모의 정확도 향상이 가능하지만, 최적 성능을 발휘하기 위해서는 수문자료동화 기법별 하이퍼-매개변수의 적정한 조정이 필요함을 함의한다.

집중형 모형 IHACRES와 GR4J를 이용한 강수 및 기온 변동성에 대한 유출 해석 민감도 평가 (Assessing the Sensitivity of Runoff Projections Under Precipitation and Temperature Variability Using IHACRES and GR4J Lumped Runoff-Rainfall Models)

  • 우동국;조지현;강부식;이송희;이가림;노성진
    • 대한토목학회논문집
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    • 제43권1호
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    • pp.43-54
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    • 2023
  • 기후변화가 고착화되면서 강수와 기온 변동으로 인한 가뭄 및 홍수 발생이 증가하고 있다. 유역 단위의 유출량 예측은 기후변화로 인한 자연재해에 대비하기 위한 수자원 관리의 시작이라 할 수 있다. 하지만, 기후변화와 유출모형의 불확실성은 정확한 유출 분석을 어렵게 한다. 본 연구에서는 이러한 불확실성을 완화하기 위하여 기후 스트레스 시나리오에 따른 두 개의 집중형 수문모형, 즉 IHACRES와 GR4J를 이용하여 강수 및 기온 변화에 따른 유출량 변화를 비교, 분석하였다. 연구 대상 지역은 합천댐과 섬진강댐 유역이며, Nash-Sutcliffe Efficiency (NSE) 및 Kling Gupta Efficiency (KGE)를 목적함수로 하여 각 모형의 매개변수를 최적화하였다. 모형의 보정과 검정은 20년(1995년-2014년)의 유출자료를 활용하였으며, 보정 및 검정 기간은 각각 7:3 비율로 설정하였다. 두 모형 모두 보정과 검정 기간에 비교적 높은 신뢰도(NSE>0.74, KGE>0.75)를 보여, 모형이 과거 사상을 재현하기에 적합하고, 모의 결과가 비교적 유사함을 확인하였다. 다음으로, 기후변동이 유출에 미치는 영향을 평가하기 위해 동일한 모의 기간에 대해 강수는 -50 %에서 +50 %의 범위를 1 %씩, 기온은 0 ℃에서 8 ℃까지 0.1 ℃씩 구분하여 총 8,181개의 기후조건 시나리오를 구축하였다. 이후, 기후 스트레스 시나리오에 따른 두 모형의 최대유량, 풍수량, 평수량을 비교 및 분석하였다. 기후 스트레스 영향을 반영한 연최대유량과 풍수량의 경우, 강수 감소에 따른 유출 패턴은 두 모형에서 비슷하였으나, 강수와 기온이 증가할수록 상이한 결과를 얻었다. 이와 반대로, 풍수량의 경우 강수와 기온 변화의 차이가 커질수록 두 모형은 유사한 결과를 얻었다. 즉, 유역의 탄력적 기후변화 대응을 위해서는 모형의 불확실성에 대한 정량적 평가가 필요하다는 것을 시사한다.

Correlation between Epidurographic Contrast Flow Patterns and Clinical Effectiveness in Chronic Lumbar Discogenic Radicular Pain Treated with Epidural Steroid Injections Via Different Approaches

  • Gupta, Ruchi;Singh, Saru;Kaur, Sukhdeep;Singh, Kulvinder;Aujla, Kuljeet
    • The Korean Journal of Pain
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    • 제27권4호
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    • pp.353-359
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    • 2014
  • Background: Epidural steroid injections are an accepted procedure for the conservative management of chronic backache caused by lumbar disc pathology. The purpose of this study was to evaluate the epidurographic findings for the midline, transforaminal and parasagittal approaches in lumbar epidural steroid injections, and correlating them with the clinical improvement. Methods: Sixty chronic lower back pain patients with unilateral radiculitis from a herniated/degenerated disc were enrolled. After screening the patients according to the exclusion criteria and randomly allocating them to 3 groups of 20 patients, fluoroscopic contrast enhanced epidural steroids were injected via midline (group 1), transforaminal (group 2) and parasagittal interlaminar (group 3) approaches at the level of the pathology. The fluoroscopic patterns of the three groups were studied and correlated with the clinical improvement measured by the VAS over the next 3 months; any incidences of complications were recorded. Results: The transforaminal group presented better results in terms of VAS reduction than the midline and parasagittal approach groups (P < 0.05). The epidurography showed a better ventral spread for both the transforaminal (P < 0.001) and the paramedian approaches (P < 0.05), as compared to the midline approach. The nerve root filling was greater in the transforaminal group (P < 0.001) than in the other two groups. The ventral spread of the contrast agent was associated with improvement in the VAS score and this difference was statistically significant in group 1 (P < 0.05), and highly significant in groups 2 and 3 (P < 0.001). In all the groups, any complications observed were transient and minor. Conclusions: The midline and paramedian approaches are technically easier and statistically comparable, but clinically less efficacious than the transforaminal approach. The incidence of ventral spread and nerve root delineation show a definite correlation with clinical improvement. However, an longer follow-up period is advisable for a better evaluation of the actual outcom.

근로자의 뇨중 상피세포에서 32P-postlabeling에 의한 발암물질의 DNA adducts측정방법에 대한 연구 (Study on Measurement of Carcinogen-DNA adducts in exfoliated urothelial cells among workers by 32P-postlabelling methods)

  • 이진헌;노재훈;그린 탈라스카
    • 한국산업보건학회지
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    • 제10권1호
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    • pp.1-17
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    • 2000
  • Carcinogen-DNA adduct analysis has potential for biomonitoring the earliest effects of exposure to many chemical carcinogens. They are the covalent reaction products of electrophiles and nucleophilic sites on DNA and the initial damage to DNA induced by many carcinogens. So many researchers begin to use them as biomarker for monitoring the earliest exposure of carcinogens and develop the effective analytical techniques about them. Randerath, Gupta and coworkers(1981, 1982) has also developed a $^{32}P$-postlabelling method as one among them. A major project for biomonitoring workers with carcinogen-DNA adducts is to develop non-invasive samples instead of tissues of target organs such as baldder and lung. This study use the exfoliated urothelial cells in urine for examine benzidine-DNA adducts. The content of exfoliated urothelial cells is not enough to significantly measure DNA content with spectrophotometer, and require the another way. So firstly washing the collected cells with PBS and 70% ethanol and centrifuge them for removing the crystals in urine, which block the isolation of DNA adducts. And then, measure the total nucleotide after $^{32}P$-postlabelling for calculating RAL. $[{\gamma}-^{32}P]ATP$ using for $^{32}P$-postlabelling, can synthesize with $[^{32}P]H_3PO_4$, and reagent and enzyme mixture (RM, EM), which is very economic in case of requiring a lot of them. Chromatography was composed of two steps. First step was to separate adduct ones from unadducted nucleotide, and secondary step was separate each adduct, which were performed with 4 kinds of solvents and different directions on TLC. With this procedure, we measure the DNA adducts in exfoliated urothelial cells of workers who were employed in benzidine and benzidine-dye company. RAL of adducts were $89.0{\times}10^7$ and $57.0{\times}10^7$ in them. In conclusion, we can significantly measure the DNA adduct in exfoliated urothelial cells by using the above $^{32}P$-postlabelling procedures, and use them to be biomonitoring workers who exposed carcinogens.

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PLASMA CONCENTRATION OF L. THYROXINE (T4). L. TRIIODOTHYRONINE (T3) AND CERTAIN OTHER BLOOD BIOCHEMICAL CONSTITUENTS IN GROWING CROSSBRED (B0S taurus × B0S indicus) CALVES

  • Shukla, D.C.;Varshney, V.P.;Gupta, P.S.P.;Mahapatro, B.B.
    • Asian-Australasian Journal of Animal Sciences
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    • 제7권1호
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    • pp.69-74
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    • 1994
  • The relationship of thyroid status and certain blood biochemical constituents with body weight gains (ADG) and age (13 to 96 weeks) was studied in Holstein Friesian ${\times}$ Hariana ($1/2F{\times}1/2H$) crossbred male calves by assessing their plasma triiodo thyronine ($T_3$), Thyroxine ($T_4$), sodium, potassium, total proteins and cholesterol level at two energy levels. Body weight gains (ADG) were higher during the 50 to 72 weeks of age and declined thereafter, the plasma $T_3$ conc. was aignificantly (p < 0.01) higher during this period compared to all other periods. There was no significant variation due to energy level. Overall mean plasma $T_3$ conc. was $1.19{\pm}0.12ng/ml$. Plasma $T_4$ conc. did not show any significant variation either between the different age periods or between the two energy levels. The mean plasma $T_4$ conc. was $37.34{\pm}1.32ng/ml$. The plasma sodium and potassium concentration did not vary significantly due to energy levels. But amongst the different age periods, sodium concentration was highest ($147.70{\pm}2.29mEq/L$) during 49-60 weeks of age and lowest ($134.70{\pm}1.78mEq/L$) during 13-24 weeks, where as for potassium concentration changes were nonsignificant. There was very little variation amongst other periods. Plasma protein level was higher at 100% energy level than at 75%. Amongst the different age period, it was significantly lower ($6.44{\pm}0.36$) during 13 to 24 weeks of age than at 37 to 48 weeks of age ($7.14{\pm}0.11$). Plasma cholesterol values were higher for 75% energy level than that of 100%. Between the periods it was highest during 61 to 72 weeks of age and the difference amongst the age period were highly significant.