Anti-diabetic Effect of <Emphasis Type="Italic">Boerhavia diffusa</Emphasis> L. Root Extract via Free Radical Scavenging and Antioxidant Mechanism

Objective

The present study was proposed to assess the in vitro free radical-scavenging activity of B. diffusa methanolic extract (BDME) and its modulatory effect against streptozotocin (STZ) induced diabetes in male Wistar rats.

Methods

Experimental diabetes was induced in Wistar albino rats by administering single dose of STZ 40 mg/kg. One week later rats with blood glucose level >200 mg/dL were segregated as diabetes in three groups each containing 6 rats in number.

Results

Total phenolic content in B. diffusa methanol extract (BDME) was found to be 87 mg of gallic acid equivalents/g extract and total flavonoid content found to be 54.1 mg of quercetin equivalents/g extract. Its extract also exhibited DPPH (IC₅₀, 163.1±6.7 μg/mL), nitric oxide (295 μg/mL) and H₂O₂ (159±5.25 μg/mL) radical scavenging activity. Pre-treatment with BDME (100 and 200 mg/kg b.w.) in streptozotocin-induced diabetic rats resulted in significant improvement in blood glucose, blood plasma enzymes SGOT, SGPT and ALP, weight loss, total protein, serum insulin and liver glycogen levels. Furthermore, it restores the activity of antioxidant enzymes viz. SOD, CAT and GPx.

Conclusion

Thus, the result suggests that BDME employed significant anti-diabetic effect in Wistar rats which is associated with its free radical scavenging and antioxidant activity.

     

“Turn the tail,not the head”: a simple,quick and inexpensive technique for the safe removal of jammed/stripped locking screws

European Journal of Orthopaedic Surgery & Traumatology - A jammed screw is a well-known complication of locking plates. Noncompliance to the standard techniques, nonusage of torque limiting...     

Risk factors for death and amputation in acute leg compartment syndrome

European Journal of Orthopaedic Surgery & Traumatology - The primary objective of this study is to determine whether time from injury to fasciotomy is associated with increased risk for death...     

An optimal control model for cloud seeding in a deterministic and stochastic environment

To promote artificial rain in India and other such developing countries, in this article, we have proposed and analyzed a nonlinear mathematical model for cloud seeding by considering that aerosols are introduced proportional to the density of water vapors present in the atmosphere. The model is analyzed using Lyapunov's stability theory of differential equations. To reduce the cost of cloud seeding, an optimal control strategy is designed by incorporating four control parameters. We have shown the existence and uniqueness of solution of this optimal control problem, using Pontryagins Maximum Principle. To minimize the cost in making artificial rain, the optimal control problem provides the strategy for the rate of introduction of aerosols in the atmosphere. To capture the effects of environmental noise on control strategies, the model in deterministic framework is converted into stochastic framework. In this regard, the Hamilton-Jacobi-Bellman equation for stochastic control cost function has been formed. The stochastic analysis implies that the control strategy is effective in reducing the cost and increasing rainfall.     

Is Use of BMP-2 Associated with Tumor Growth and Osteoblastic Differentiation in Murine Models of Osteosarcoma?

BackgroundThe putative benefit of rhBMP-2 is in the setting of limb reconstruction using structural allografts, whether it be allograft-prosthetic composites, osteoarticular allografts, or intercalary segmental grafts. There are also potential advantages in augmenting osseointegration of uncemented endoprosthetics and in reducing infection. Recombinant human BMP-2 might mitigate nonunion in structural allograft augmented osteosarcoma limb salvage surgery; however, its use is limited because of concerns about the prooncogenic effects of the agent.Questions/purposes(1) To assess if BMP-2 signaling influences osteosarcoma cell line growth. (2) To characterize degree of osteosarcoma cell line osteoblastic differentiation in response to BMP-2. (3) To assess if BMP-2 signaling has a consistent effect on local or systemic tumor burden in various orthotopic murine models of osteosarcoma.MethodsIn this study, 143b, SaOS-2 and DLM8-M1 osteosarcoma cell lines were transfected with BMP-2 cDNA controlled by a constitutive promoter (experimental) or an empty vector (control) using a PiggyBac transposon system. Cellular proliferation was assessed using a quantitative MTT colorimetric assay. Osteoblastic differentiation was compared between control and experimental cell lines using quantitative real-time polymerase chain reaction of the osteoblastic markers connective tissue growth factor, Runx-2, Osterix, alkaline phosphatase and osteocalcin. Experimental and control cell lines were injected into the proximal tibia of either NOD-SCID (143b and SaOS-2 xenograft model), or C3H (DLM8-M1 syngeneic model) mice. Local tumor burden was quantitatively assessed using tumor volume caliper measurements and bioluminescence, and qualitatively assessed using post-mortem ex vivo microCT. Lung metastasis was qualitatively assessed by the presence of bioluminescence, and incidence was confirmed using histology. rhBMP-2 soaked absorbable collagen sponges (experimental) and sterile-H₂O soaked absorbable collagen sponges (control) were implanted adjacent to 143b proximal tibial cell line injections to compare the effects of exogenous BMP-2 application with endogenous upregulation.ResultsConstitutive expression of BMP-2 increased the in vitro proliferation of 143b cells (absorbance values 1.2 ± 0.1 versus 0.89 ± 0.1, mean difference 0.36 [95% CI 0.12 to 0.6]; p = 0.01), but had no effect on SaOS-2 and DLM8-M1 cell proliferation. In response to constitutive BMP-2 expression, 143b cells had no differences in osteoblastic differentiation, while DLM8-M1 cells downregulated the early marker connective tissue growth factor (mean ΔCt 0.2 ± 0.1 versus 0.6 ± 0.1; p = 0.002) and upregulated the early-mid range marker Runx-2 (mean ΔCt -0.8 ± 0.1 versus -1.1 ± 0.1; p = 0.002), and SaOS-2 cells upregulated the mid-range marker Osterix (mean ΔCt -2.1 ± 0.6 versus -3.9 ± 0.6; p = 0.002). Constitutive expression of BMP-2 resulted in greater 143b and DLM8-M1 local tumor volume (143b: 307.2 ± 106.8 mm³ versus 1316 ± 387.4 mm³, mean difference 1009 mm³ [95% CI 674.5 to 1343]; p < 0.001, DLM8-M1 week four: 0 mm³ versus 326.1 ± 72.8 mm³, mean difference 326.1 mm³ [95% CI 121.2 to 531]; p = 0.009), but modestly reduced local tumor growth in SaOS-2 (9.5 x 10⁸ ± 8.3x10⁸ photons/s versus 9.3 x 10⁷ ± 1.5 x 10⁸ photons/s, mean difference 8.6 x 10⁸ photons/s [95% CI 5.1 x 10⁸ to 1.2 x 10⁹]; p < 0.001). Application of exogenous rhBMP-2 also increased 143b local tumor volume (495 ± 91.9 mm³ versus 1335 ± 102.7 mm³, mean difference 840.3 mm³ [95% CI 671.7 to 1009]; p < 0.001). Incidence of lung metastases was not different between experimental or control groups for all experimental conditions.ConclusionsAs demonstrated by others, ectopic BMP-2 signaling has unpredictable effects on local tumor proliferation in murine models of osteosarcoma and does not consistently result in osteosarcoma cell line differentiation. Further investigations into other methods of safe bone and soft tissue healing augmentation and the use of differentiation therapies is warranted.Clinical RelevanceOur results indicate that BMP-2 has the potential to stimulate the growth of osteosarcoma cells that are poorly responsive to BMP-2 mediated osteoblastic differentiation. As this differentiation potential is unpredictable in the clinical setting, BMP-2 may promote the growth of microscopic residual tumor burden after resection. Our study provides further support for the recommendation to avoid the use of BMP-2 after limb-salvage surgery in patients with osteosarcoma.     

A Pilot Study Investigating the Dynamics of Pigeon Circovirus Recombination in Domesticated Pigeons Housed in a Single Loft

Pigeon circovirus (PiCV) infects pigeon populations worldwide and has been associated with immunosuppression in younger pigeons. Recombination is a common mechanism of evolution that has previously been shown in various members of the Circoviridae family, including PiCV. In this study, three groups of pigeons acquired from separate lofts were screened for PiCV, and their genome sequence was determined. Following this, they were housed in a single loft for 22 days, during which blood and cloacal swab samples were taken. From these blood and cloacal swabs, PiCV genomes were determined with the aim to study the spread and recombination dynamics of PiCV in the birds. Genome sequences of PiCV were determined from seven pigeons (seven tested PiCV positive) before they were housed together in a loft (n = 58 sequences) and thereafter from the ten pigeons from blood and cloacal swabs (n = 120). These 178 PiCV genome sequences represent seven genotypes (98% pairwise identity genotype demarcation), and they share >88% genome-wide pairwise identity. Recombination analysis revealed 13 recombination events, and a recombination hotspot spanning the 3′ prime region, the replication-associated protein (rep) gene and the intergenic region. A cold spot in the capsid protein-coding region of the genome was also identified. The majority of the recombinant regions were identified in the rep coding region. This study provides insights into the evolutionary dynamics of PiCV in pigeons kept under closed rearing systems.     

Design,Synthesis, Biological Screening,and Molecular Docking Studies of Piperazine-Derived Constrained Inhibitors of DPP-IV for the Treatment of Type 2 Diabetes

Novel piperazine-derived conformationally constrained compounds were designed, synthesized, and evaluated for in vitro Dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. From a library of compounds synthesized, 1-(2-(4-(7-Chloro-4-quinolyl)piperazin-1-yl)acetyl)pyrrolidine ( 2g ) was identified as a potential DPP-IV inhibitor exhibiting better inhibitory activity than P32/98, reference inhibitor. The in vivo studies carried out in STZ and db/db mice models indicated that the compound 2g showed moderate antihyperglycemic activity as compared to the marketed drug Sitagliptin. A two-week repeated dose study in db/db mice revealed that compound 2g significantly declined blood glucose levels with no evidence of hypoglycemia risk. Furthermore, it showed improvement in insulin resistance reversal and antidyslipidemic properties. Molecular docking studies established good binding affinity of compound 2g at the DPP-IV active site and are in favor of the observed biological data. These data collectively suggest that compound 2g is a good lead molecule for further optimization studies.     

Development and validation of a questionnaire to assess socio-behavioural impact of COVID-19 on the general population

Background and aimThe aim of the study is to develop a valid and reliable tool to assess sociobehavioural changes due to COVID among the general population.MethodsThis mixed method study has two phases. Phase I for questionnaire development (literature review, focus group discussion, expert evaluation and pilot testing). Phase II for establishing construct validity via factor analysis and internal consistency via Cronbach’s ɑ by administering the questionnaire on 179 participants.ResultsA questionnaire comprising 33 questions and five domains was developed having Cronbach’s α of 0·82.ConclusionThe developed questionnaire is a concise, easy to administer and valid tool to assess socio-behavioural changes.