Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial.

BACKGROUND: Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in a phase I/II multicenter trial (NCT01631552) in patients with advanced epithelial cancers. This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously. PATIENTS AND METHODS: Patients with refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic parameters with investigator-evaluated objective response rate (ORR per RECIST 1.1), duration of response, clinical benefit rate, progression-free survival, and overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and castrate-resistant prostate cancer. RESULTS: In the OSP (n = 495, median age 61 years, 68% female; UGT1A1∗28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently discontinued treatment due to adverse events (AEs). Most common treatment-related AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade ≥3 neutropenia and febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. Neutropenia (all grades) was numerically more frequent in UGT1A1∗28 homozygotes (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1∗1 wild type (59/177; 33.3%). There was one treatment-related death due to an AE of aspiration pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant prostate cancer patient had a complete response (n = 1/11; 9.1% ORR). CONCLUSIONS: SG demonstrated a toxicity profile consistent with previous published reports. Efficacy was seen in several cancer cohorts, which validates Trop-2 as a broad target in solid tumors.

Simulations of single- and two-tone Tm-doped optical fiber laser amplifiers.

This work uses numerical simulations of a thulium-doped optical fiber amplifier to predict various performance characteristics such as peak temperatures, expected output powers and efficiencies, presence of amplified spontaneous emission (ASE), and transverse mode instability (TMI) onset power thresholds. Single- and two-tone configurations are studied. In the latter case, the two laser sources are separated in frequency by the amount that corresponds to the peak Raman gain, and a few seed ratios at various total seed powers are examined. The goal is to provide the field with pertinent information on what is feasible for this type of amplifier.

Development of a system to measure color in fresh and microwave dried banana slices.

The main focus of this study was to develop and calibrate a computerized image analysis system in order to measure the color of banana (Musa Cavendish) under microwave treatment. Bananas were cut into 2 mm slice thickness and dried at two different microwave power level; 540 W and 180 W. An algorithmic was developed which converted RGB color value from a color image into CIE L*a*b* values very well (ErrorL* = 2.163%, Errora* = 4.458%, Errorb* = 5.224%). Once the calibration is completed, it was applied to measure the color change in the banana slice during drying. The value of L* decreased from 89.01 to 71.17 and from 82.60 to 72.53 for both microwave treated samples suggesting browning is taking place during the drying operation. The value of a* increased from - 0.80 to 11.50 and from - 3.90 to 5.18 for 540 and 180 W microwave treated banana slices respectively suggesting tendency of redness increased. The same type of increment was observed for b* value. It changed from 36.46 to 60.51 and 34.02 to 72.82 for 540 and 180 W microwave treated banana slices, respectively. Artificial Neural Network (ANN) modeling was used for prediction of the developed CVS's values.

Sacituzumab govitecan in previously treated hormone receptor-positive/HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial.

BACKGROUND: Trophoblast cell-surface antigen-2 (Trop-2) is expressed in epithelial cancers, including hormone receptor-positive (HR+) metastatic breast cancer (mBC). Sacituzumab govitecan (SG; Trodelvy®) is an antibody-drug conjugate composed of a humanized anti-Trop-2 monoclonal antibody coupled to SN-38 at a high drug-to-antibody ratio via a unique hydrolyzable linker that delivers SN-38 intracellularly and in the tumor microenvironment. SG was granted accelerated FDA approval for metastatic triple-negative BC treatment in April 2020. PATIENTS AND METHODS: We analyzed a prespecified subpopulation of patients with HR+/human epidermal growth factor receptor 2-negative (HER2-) HR+/HER2- mBC from the phase I/II, single-arm trial (NCT01631552), who received intravenous SG (10 mg/kg) and whose disease progressed on endocrine-based therapy and at least one prior chemotherapy for mBC. End points included objective response rate (ORR; RECIST version 1.1) assessed locally, duration of response (DOR), clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Fifty-four women were enrolled between 13 February 2015 and 1 June 2017. Median (range) age was 54 (33-79) years and all received at least two prior lines of therapy for mBC. At data cut-off (1 March 2019), 12 patients were still alive. Key grade ≥3 treatment-related toxicities included neutropenia (50.0%), anemia (11.1%), and diarrhea (7.4%). Two patients discontinued treatment due to treatment-related adverse events. No treatment-related deaths occurred. At a median follow-up of 11.5 months, the ORR was 31.5% [95% confidence interval (CI), 19.5%-45.6%; 17 partial responses]; median DOR was 8.7 months (95% CI 3.7-12.7), median PFS was 5.5 months (95% CI 3.6-7.6), and median OS was 12 months (95% CI 9.0-18.2). CONCLUSIONS: SG shows encouraging activity in patients with pretreated HR+/HER2- mBC and a predictable, manageable safety profile. Further evaluation in a randomized phase III trial (TROPiCS-02) is ongoing (NCT03901339). TRIAL REGISTRATION: ClinicalTrials.gov NCT01631552; https://clinicaltrials.gov/ct2/show/NCT01631552.

Determination of immune status in dogs against CPV-2 by recombinant protein based latex agglutination test.

Canine parvoviral enteritis is a highly contagious viral illness caused by canine parvovirus-2 (CPV-2) which affects puppies of mainly 6-20 weeks of age. Vaccination is pivotal in preventing and controlling CPV-2 infection. Determination of antibody status is a critical determinant for successful vaccination. The hemagglutination inhibition (HI) test is 'gold standard' test for quantification of antibodies specific to CPV-2, although the execution of this test is not feasible under field conditions. The present study was undertaken to develop a point of care testing to determine immune status prior to CPV-2 vaccination or to detect seroconversion in immunized dogs by latex agglutination test (LAT) using recombinant antigen. Truncated portion of VP2 protein (tVP2) of CPV-2 was selected on the basis of antigenic indices, overexpressed the recombinant protein in E. coli system and was subsequently used in development of LAT. A total of 59 serum samples obtained from vaccinated (n = 54) and healthy unvaccinated (n = 5) dogs were tested. The positivity was observed in 85% (46/54) of these dogs with varying agglutination pattern. The overall sensitivity and specificity of latex agglutination test in comparison to HI test was recorded as 90% and 88% respectively with an agreement value of 90% (CI = 95%).

Antisperm antibodies in repeat-breeding cows: Frequency, detection and validation of threshold levels employing sperm immobilization, sperm agglutination and immunoperoxidase assay.

Antisperm antibodies have been found in repeat-breeding(RB) cows, and those causing agglutination and/or immobilization of sperm are considered to be closely related to unexplained infertility. However, a standard protocol for identifying antisperm antibodies (ASA) in cattle is not validated. Therefore, an investigation was undertaken to evaluate sperm immobilization (SIT), sperm agglutination (SAT) and immunoperoxidase (IPT)assays for detection of ASA in serum and their respective threshold levels for confirmation. Animals (heifers, normally breeding, repeat-breeding and pregnant animals) that were free from IBR, brucellosis and uterine infections (screened by clinical examination) were included in the study. Sperm agglutinating, sperm immobilizing and antisperm antibodies evaluated by respective assay were significantly higher (p < .05) in RB cows compared to other groups. The SIT assay was able to identify 61% of RB caused by ASA, more than those employing SAT and IPT. Furthermore, a dilution rate of 1:5 and 1:80 (confirms 59.0 and 57.0% RB+ve)were sufficient to diagnose ASA by SAT and IPT, respectively. Results indicate the presence of __12.6% clumped spermatozoa and __ 2.6%(cut-off value) peroxidase-positive spermatozoa at 1:5 and 1:80 dilutions diagnosed with SAT and IPT, respectively, may be considered as repeaters arising out of ASA. Furthermore, study also showed the presence of lower incidence of ASA positivity in other groups of animals (heifer

Comparative diagnostic evaluation of OMP31 gene based TaqMan® real-time PCR assay with visual LAMP assay and indirect ELISA for caprine brucellosis.

Brucellosis is one of the leading causes of abortion in domestic animals that imposes costs on both economy and society. The disease is highly zoonotic and poses risk to animal handlers due to its zoonotic nature. It causes stillbirth, loss of kids and abortion in last term of pregnancy. Reproductive damage includes infertility in does and orchitis and epididymitis in breeding bucks, which result in high financial losses to farmers and the agriculture industry as a whole. It requires highly sensitive and specific assays to diagnose the disease at field level. In the current study, a visual loop-mediated isothermal amplification (LAMP) assay and the TaqMan® real-time PCR were developed with high sensitivity and specificity. For the TaqMan® probe, real-time PCR primers were developed using Omp31 gene as target and primers were designed using discontiguous conserved sequences of Omp31 gene. The Omp31 probes were designed by attaching 6-FAM reporter dye at the 5' end and BHQ-1 quencher at the 3' end. Published primers were used for visual LAMP assay targeting the Omp25 gene. Sensitivity of the standardized visual LAMP assay and TaqMan® real-time PCR assay was determined by serial dilution of positive Brucella melitensis DNA (102 to 10-4 ng) obtained from standard culture. The TaqMan® probe real-time assay can detect as low as 100 fg of B. melitensis DNA, whereas culture from vaginal swab washings has a limit of detection (LOD) of only 1 cfu/ml. Similarly, the visual LAMP assay can detect as low as 10 fg of B. melitensis DNA as compared to an LOD of 30 cfu/ml from culture of vaginal swab washings. Both assays were compared with serological tests (serum tube agglutination test (STAT) and indirect enzyme-linked immunosorbent assay (iELISA)) for diagnostic sensitivity and specificity. Diagnostic sensitivities and specificities for TaqMan® real-time PCR vs. LAMP assays were 98 and 100% vs. 100 and 97.8%, respectively. Results of visual LAMP assay indicated that LAMP is a fast, specific, sensitive, inexpensive and suitable method for diagnosis of B. melitensis infection under field conditions. On the other hand, Omp31 TaqMan® probe real-time assay can be used in conjunction with the other field-based diagnostic tests due to its high specificity.

TiO2 Nanowires/Poly(Methyl Methacrylate) Based Hybrid Photodetector: Improved Light Detection.

Hybrid photodetector with a maximum external quantum efficiency of ~3.08% in the UV region at 370 nm, was fabricated by spin-coated poly(methyl methacrylate) (PMMA) polymer onto glancing angle deposited (GLAD) vertically aligned TiO2 nanowire (NW) arrays. The TiO2 NWs/PMMA detector shows excellent rectification and constant 1.3 times photo-responsivity in the reverse bias condition from -1 V to -10 V. The photodiode possesses a low ideality factor of 5.1 as compared to bared TiO2 NWs device of 7.1. The hybrid device produces sharp turn-on of -0.8 s and turn-off transient of -0.9 s respectively.

Risk assessment for anterior cruciate ligament injury.

INTRODUCTION: Anterior cruciate ligament tears are one of the most frequent soft tissue injuries of the knee. A torn anterior cruciate ligament leaves the knee joint unstable and at risk for further damage to other soft tissues manifested as pain, dislocation, and osteoarthritis. A better understanding of the anatomical details of knee joints suffering anterior cruciate ligament tears is needed to understand and develop prediction models for anterior cruciate ligament injury and/or tear. MATERIALS AND METHODS: Magnetic resonance images of 32 patients with anterior cruciate ligament tears and 40 patients with non-tears were evaluated from a physician group practice. Digital measurements of femoral condyle length, femoral notch width, anterior cruciate ligament width in the frontal and sagittal plane, and the anterior cruciate ligament length in the sagittal plane were taken in both groups to identify trends. Monte Carlo simulations were performed (n = 2000) to evaluate the relationship between notch width index and sagittal width and to establish functional relationships among the anatomical parameters for potential injury risk. Sensitivity analysis performed shows the risk of anterior cruciate ligament injury a function of force and notch width index. RESULTS: Females have a significantly shorter anterior cruciate ligament when compared to that of males. The notch width index was also significantly different between torn and non-torn individuals. The NWI was not significantly different between genders (p value = 0.40). CONCLUSIONS: Anterior cruciate ligament injury has been shown to be caused by the forces which act on the ligament. These forces can result from hyperextension of the tibia or the internal rotation of tibia. The anatomical parameters of the knee joint (i.e., notch width index, anterior cruciate ligament width and length) have no role in the cause of an injury.

Modeling of gas transmission properties of polymeric films used for MA packaging of fruits.

High value fruits namely, apple (cv. Royal Delicious), guava (cv. Baruipur) and litchi (cv. Shahi) harvested at their commercial maturity were considered for MA packaging to enhance storage life. Polymeric films namely LDPE, BOPP, PVC, PVDC of different thickness were used for MA packaging study and various film characteristics such as gas transmission rates, water vapour transmission rate, clarity, strength and durability were evaluated. Mathematical model was developed based on Arrhenius type equation to predict gas transmission rate (GTR) and the developed model was found to be very good fit with the mean relative deviation modulus value quite less than 10 %. The GTR of the films increased with the increase in storage temperature and the magnitude of the increase varied with the film type and thickness. Regression models have been suitably developed to predict the oxygen transmission rate and carbon dioxide transmission rate of selected polymeric films and combined film laminates as a function of temperatures. Since, none of the individual films could meet the gas transmission requirements of MAP for selected fruits, two different films were tailored to form laminates that sufficed the requirements for prolonged storage with maintaining original quality.

Development and validation of a comprehensive model for map of fruits based on enzyme kinetics theory and arrhenius relation.

MAP is a dynamic system where respiration of the packaged product and gas permeation through the packaging film takes place simultaneously. The desired level of O2 and CO2 in a package is achieved by matching film permeation rates for O2 and CO2 with respiration rate of the packaged product. A mathematical model for MAP of fresh fruits applying enzyme kinetics based respiration equation coupled with the Arrhenious type model was developed. The model was solved numerically using MATLAB programme. The model was used to determine the time to reach to the equilibrium concentration inside the MA package and the level of O2 and CO2 concentration at equilibrium state. The developed model for prediction of equilibrium O2 and CO2 concentration was validated using experimental data for MA packaging of apple, guava and litchi.

TiO2 embedded Si nanowire network based Schottky detector for enlarged light detection.

The Si nanowire (NW) network was fabricated on the Si substrate with the help of glancing angle synthesized Ag NPs assisted etching technique. The horizontal Si NWs network was characterized by field emission gun-scanning electron microscopy which shows the formation of long Si NWs of diameter within the range of 110-180 nm. The TiO2 thin film (TF) was deposited on the Si NWs, which shows -2.5 times enlarged optical absorption than that of bare Si substrate. Ag-TiO2 contacts exhibit Schottky behaviour and higher photoconduction was observed for TiO2-Si NW detector than that of TiO2 TF under illumination. The dark currents of TiO2 TF and TiO2-Si NW devices were exerted to be 0.1 mA/cm2 and 0.2 mA/cm2 at +1 V, which increased to 0.2 mA/cm2 and 1.23 mA/cm2, respectively, under the illumination of 100 W filament bulb. A threefold enhanced photodetection for the Si NW device was observed compared to the TiO2 TF device. The nonlinear rise of photocurrent of 2 x 10(-2) mA/cm2, after 5 min light illumination was observed due to carrier diffusion effect.

Design and development of modified atmosphere packaging system for guava (cv. Baruipur).

Modified atmosphere packaging (MAP) is a dynamic system during which respiration and permeation occur simultaneously. Hence factors affecting both respiration and permeation were considered for designing a package. In the design of MA packages for guava (cv. Baruipur) a total of 13 variables were considered. The independent variables includes: weight of fruits, surface area of packaging film, free volume of the package, thickness of the film and permeabilities of film to O2 and CO2 gas. The fixed variables considered were: the surrounding gas composition and temperature, the respiration rates for O2 consumption and CO2 evolution, and the equilibrium gas compositions to be attained in the package so that the fruit's shelf-life is extended. Two types of MA packages, having package size of 19 cm × 19 cm for a fill weight of 1,000 ± 100 g were developed. Packages were designed to accommodate a fill weight range of 0.90-1.10 kg. Various package parameters were optimized to facilitate establishment of dynamic equilibrium at target levels of O2 and CO2 concentration in the package. The storage study of MA packages was performed at 10, 15, 20 and 25 °C temperatures. The performance of film packages was evaluated for their ability to establish equilibrium at target levels and to extend the shelf life of the packaged fruit. The MA packaging system increased the shelf life of guava by 128-200 % compared to the unpacked fruits at various storage temperatures with a quality comparable with the freshly harvested commodity.

Adoptive cell therapy for high grade gliomas using simultaneous temozolomide and intracranial mgmt-modified γδ t cells following standard post-resection chemotherapy and radiotherapy: current strategy and future directions.

Cellular therapies, including chimeric antigen receptor T cell therapies (CAR-T), while generally successful in hematologic malignancies, face substantial challenges against solid tumors such as glioblastoma (GBM) due to rapid growth, antigen heterogeneity, and inadequate depth of response to cytoreductive and immune therapies, We have previously shown that GBM constitutively express stress associated NKG2D ligands (NKG2DL) recognized by gamma delta (γδ) T cells, a minor lymphocyte subset that innately recognize target molecules via the γδ T cell receptor (TCR), NKG2D, and multiple other mechanisms. Given that NKG2DL expression is often insufficient on GBM cells to elicit a meaningful response to γδ T cell immunotherapy, we then demonstrated that NKG2DL expression can be transiently upregulated by activation of the DNA damage response (DDR) pathway using alkylating agents such as Temozolomide (TMZ). TMZ, however, is also toxic to γδ T cells. Using a p140K/MGMT lentivector, which confers resistance to TMZ by expression of O(6)-methylguanine-DNA-methyltransferase (MGMT), we genetically engineered γδ T cells that maintain full effector function in the presence of therapeutic doses of TMZ. We then validated a therapeutic system that we termed Drug Resistance Immunotherapy (DRI) that combines a standard regimen of TMZ concomitantly with simultaneous intracranial infusion of TMZ-resistant γδ T cells in a first-in-human Phase I clinical trial (NCT04165941). This manuscript will discuss DRI as a rational therapeutic approach to newly diagnosed GBM and the importance of repeated administration of DRI in combination with the standard-of-care Stupp regimen in patients with stable minimal residual disease.

Piper nigrum and piperine: an update.

Black pepper (Piper nigrum L.) is a very widely used spice, known for its pungent constituent piperine. However, in addition to its culinary uses, pepper has important medicinal and preservative properties, and, more recently, piperine has been shown to have fundamental effects on p-glycoprotein and many enzyme systems, leading to biotransformative effects including chemoprevention, detoxification, and enhancement of the absorption and bioavailability of herbal and conventional drugs. Based on modern cell, animal, and human studies, piperine has been found to have immunomodulatory, anti-oxidant, anti-asthmatic, anti-carcinogenic, anti-inflammatory, anti-ulcer, and anti-amoebic properties. In this review, the chemical constituents, biological activities, effects of processing, and future potential of black pepper and piperine have been discussed thoroughly.

Effect of Varying the Energy Density of Protein-adequate Diets on Nutrient Metabolism, Clinical Chemistry, Immune Response and Growth of Muzaffarnagari Lambs.

Effects of varied dietary energy densities on immune response and performance of Muzzafarnagari lambs were ascertained in a 180-d study. Animals (n = 24), in three groups, were fed diets providing 100% (100E), 80% (80E) or 70% (70E) of their metabolizable energy requirement. Mean nutrient digestibilities varied significantly among treatments. Nitrogen intake was lower (p<0.01) in the 70E. Nitrogen retention, was reduced (p<0.001) in 80E and 70E vs 100E. The average daily gain (p<0.001) was 47.01±4.23, 13.54±1.72 and -16.67±8.24 g for 100E, 80E and 70E, respectively. Hemoglobin concentration, haematocrit, total and differential leukocyte counts were lower (p<0.001) for 80E and 70E than for 100E with a similar trend (p<0.05) for serum glucose and total protein. Serum cortisol was reduced (p<0.001) with decreased energy availability. Antibody titre to Brucella abortus S19 showed an initial reduction in 80E and 70E vs 100E. Delayed-type hypersensitivity response was lower (p<0.001) in 80E and 70E vs 100E, accompanying a lower (p<0.001) nitric oxide production by the peripheral lymphocytes. It is concluded that the reduced dietary energy density significantly affects the growth performance and immune response of lambs.

Optical biosensors: a revolution towards quantum nanoscale electronics device fabrication.

The dimension of biomolecules is of few nanometers, so the biomolecular devices ought to be of that range so a better understanding about the performance of the electronic biomolecular devices can be obtained at nanoscale. Development of optical biomolecular device is a new move towards revolution of nano-bioelectronics. Optical biosensor is one of such nano-biomolecular devices that has a potential to pave a new dimension of research and device fabrication in the field of optical and biomedical fields. This paper is a very small report about optical biosensor and its development and importance in various fields.

Study of color kinetics of banana (Musa cavendish) under microwave drying by application of image analysis.

Microwave drying works on the volumetric heating concept promoted by electromagnetic radiation at 0.915 or 2.450 GHz. In this study, banana (Musa Cavendish) was taken as the sample and treated under microwave drying. The effect of two process variables, namely slice thickness (2, 3.5, and 5 mm) and microwave power (180 W, 360 W, and 540 W), were studied on drying kinetics and color kinetics. It was observed that the inverse variation relationship exists between drying time and microwave power level while drying time and slice thickness exhibited a direct variation relationship. A Computer Vision System (CVS) was developed to measure the color values of banana in CIELab space using an algorithm written in MATLAB software. Once the color parameters were obtained, they were fitted in First and Zero-order kinetic models. Both models were found to describe the color values adequately. This study concludes that microwave drying is a promising dehydration technique for banana drying that reduces the significant time of drying. Application of CVS is an excellent approach to measure the surface color of banana.

Effects of Nandrolone and TGF-beta1 in growing rabbits with osteopenia induced by over-supplementation of calcium and vitamin D3.

The study was undertaken to find out the effects of over supplementation of dietary calcium and vitamin D3 on the mineralization of growing skeleton, taking rabbit as an animal model; further to study the effects of Nandrolone deconoate and TGF-beta1 on the mineralization of osteopenic bones. Twenty four New Zealand White rabbits of either sex, 60 day old, were randomly divided in 4 equal groups, A, B, C and D. The animals of groups B, C and D were administered with oral supplementation of calcium (2000 mg/kg of standard rabbit feed) and vit-D3 (1000 IU/kg of standard feed) for 60 days. The animals of group A were given standard ration without any supplementation. After 60 days, the Ca-vit.D3 supplementation was discontinued; and the animals of group C were administered with TGF-beta1 (10 ng, i.m.) once in every three days and animals of group D were given Nandrolone deconoate (10 mg, i.m.) once every week for 30 days, whereas in animals of group B, no treatment was given. All the animals were evaluated based on different observations like body weight, radiographic observations, circulating biochemical and hormone profile (plasma Ca, IP, AP, OC and iPTH) every 15 days up to 60 days after initiation of treatment. The results indicated that the body weight of rabbits in different groups increased gradually and steadily at different intervals till the end of observation period, however, the increase was non-significantly more in group D. The CI in group A increased gradually at different intervals; whereas in groups B, C and D, there was no appreciable increase in the CI during the period of Ca-vit.D3 supplementation, suggesting development of osteopenia. Treatment with TGF-beta1 did not increase the CI significantly, whereas Nandrolone treatment resulted in significant increase in the CI on days 45 and 60. The plasma Ca levels showed slight but gradual increase from day 0 to 60 in almost all groups. Subsequently also, there was no marked change at different intervals in groups A and B; however, significant reduction in plasma Ca was noticed in group C on 15(th) day and in group D on 60(th) day after initiation of treatment. Plasma IP levels in groups B and C showed a decreasing trend up to day 60. After discontinuation of Ca-vit.D3 supplementation, in group B, it further decreased to remain significantly lower on 15(th) day, and in groups C and D, it increased significantly on 60(th) post-treatment day. There was no significant change in the AP activity during the entire period of study in group A; whereas significant reduction in AP activity was measured on 30(th) and 60(th) days of treatment in groups B and C, and on 15(th) day of treatment in group D. Plasma iPTH values did not show any significant change at any interval during the first 60 days in all groups. On 30(th) and 60(th) days of treatment, the mean iPTH level remained significantly lesser in group B. In all groups treated with over supplementation of Ca and vit.D3, there was a non-significant increase in the plasma OC levels up to day 60; however, there was no significant difference between the groups. It can be concluded that additional supplementation of Ca and vit.D3 results in osteopenia in growing rabbits. Administration of Nandrolone helps to increase the mineral density in osteopenic bones, whereas TGF-beta1 does not seem to have positive effect on the skeletal mineralization.