Cost variation analysis of antihypertensive drugs acting through renin angiotensin aldosterone axis modulation

Background: Several brands of antihypertensive drugs are available in the Indian market with huge price variations. This study was undertaken to find out the percentage cost variation and cost ratio of antihypertensive drugs acting through renin angiotensin aldosterone axis modulation.Methods: Costs of different brands of renin angiotensin aldosterone axis modulatory drugs with antihypertensive action for the same dosage form and strength were found out using current index of medical specialties-134, July-October 2016. The maximum and minimum price of different brands of each drug was noted. Data was entered in Microsoft excel 2010. Percentage cost variation and cost ratio was calculated for each drug.Results: 16 antihypertensive drugs were analysed. Most of them were tablets. Ramipril and Valsartan were available as capsules also. Among tablets, percentage cost variation was highest for Atenolol 12.5 mg (683.93%) and least for Bisoprolol 2.5 mg (3.6538%). Valsartan capsules (160 mg) had no difference in the costs between the available 2 brands. Cost ratio ranged from 1.04 to 7.84 among the tablet form of drugs.Conclusions: There is a huge difference in the cost of antihypertensive drugs manufactured by different companies in the same strength and dosage form. To promote rational drug use and cost effective therapy, it is essential to create an awareness among clinicians regarding the availability of multiple brands for these drugs and the discrepancies in their costs

Variations of great saphenous vein: a cadaveric study in central Indian population

Background: Variations are more commonly seen in venous system as compared to arterial system. Varicosities are more commonly seen in the superficial veins of lower limbs.Methods: In the present study, thirty lower limbs were dissected superficially to study the course, tributaries and perforators of great saphenous vein. After exposing the vein, we took various measurements from saphenofemoral junction to the origin of various tributaries and perforators. Pattern of duplications were also reported.Results: The mean distance of tributaries and perforators were compared with the previous literature available. Patterns of duplication were also reported.Conclusions: Study of variations of great saphenous vein would be of immense help in planning varicose vein treatment and coronary artery bypass procedures where it is used as autograft. Therefore, the study will be helpful for surgeons, cardiologist and interventional radiologist

Studying the Effects of Sex-related Differences on Brain Age Prediction using brain MR Imaging

While utilizing machine learning models, one of the most crucial aspects is how bias and fairness affect model outcomes for diverse demographics. This becomes especially relevant in the context of machine learning for medical imaging applications as these models are increasingly being used for diagnosis and treatment planning. In this paper, we study biases related to sex when developing a machine learning model based on brain magnetic resonance images (MRI). We investigate the effects of sex by performing brain age prediction considering different experimental designs: model trained using only female subjects, only male subjects and a balanced dataset. We also perform evaluation on multiple MRI datasets (Calgary-Campinas(CC359) and CamCAN) to assess the generalization capability of the proposed models. We found disparities in the performance of brain age prediction models when trained on distinct sex subgroups and datasets, in both final predictions and decision making (assessed using interpretability models). Our results demonstrated variations in model generalizability across sex-specific subgroups, suggesting potential biases in models trained on unbalanced datasets. This underlines the critical role of careful experimental design in generating fair and reliable outcomes

Mechanism of Mg 2+ -accompanied product release in sugar nucleotidyltransferases

The nucleotidyl transfer reaction, catalyzed by sugar nucleotidyltransferases (SNTs), is assisted by two active site Mg 2+ ions. While studying this reaction using X-ray crystallography, we captured snapshots of the pyrophosphate (product) as it exits along a pocket. Surprisingly, one of the active site Mg 2+ ions remains coordinated to the exiting pyrophosphate. This hints at the participation of Mg 2+ in the process of product release, besides its role in catalyzing nucleotidyl transfer. These observations are further supported by enhanced sampling molecular dynamics simulations. Free energy computations suggest that the product release is likely to be rate limiting in SNTs, and the origin of the high free energy barrier for product release could be traced back to the “slow” conformational change of an Arg residue at the exit end of the pocket. These results establish a dual role for Mg 2+, and propose a general mechanism of product release during the nucleotidyl transfer by SNTs

A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment

Cancer-associated fibroblasts (CAFs) are one of the most prominent cell types in the stromal compartment of the tumor microenvironment. CAFs support multiple aspects of cancer progression, including tumor initiation, invasion, and metastasis. The heterogeneous nature of the stromal microenvironment is attributed to the multiple sources from which the cells in this compartment originate. The present study provides the first evidence that cancer stem cells (CSCs) are one of the key sources of CAFs in the tumor niche. We generated CSC-like cells by treating mouse induced pluripotent stem cells with conditioned medium from breast cancer cell lines. The resulting cell population expressed both CSC and pluripotency markers, and the sphere-forming CSC-like cells formed subcutaneous tumors in nude mice. Intriguingly, these CSC-like cells always formed heterogeneous populations surrounded by myofibroblast-like cells. Based on this observation, we hypothesized that CSCs could be the source of the CAFs that support tumor maintenance and survival. To address this hypothesis, we induced the differentiation of spheres and purified the myofibroblast-like cells. The resulting cells exhibited a CAF-like phenotype, suggesting that they had differentiated into the subpopulations of cells that support CSC self-renewal. These findings provide novel insights into the dynamic interplay between various microenvironmental factors and CAFs in the CSC niche

Microenvironment of mammary fat pads affected the characteristics of the tumors derived from the induced cancer stem cells

Breast cancer is the first common cause of cancer-related death in women worldwide. Since the malignancy and aggressiveness of breast cancer have been correlated with the presence of breast cancer stem cells, the establishment of a disease model with cancer stem cells is required for the development of a novel therapeutic strategy. Here, we aimed to evaluate the availability of cancer stem cell models developed from mouse induced pluripotent stem cells with the conditioned medium of different subtypes of breast cancer cell lines, the hormonal-responsive T47D cell line and the triple-negative breast cancer BT549 cell line, to generate in vivo tumor models. When transplanted into the mammary fat pads of BALB/c nude mice, these two model cells formed malignant tumors exhibiting pronounced histopathological characteristics similar to breast cancers. Serial transplantation of the primary cultured cells into mammary fat pads evoked the same features of breast cancer, while this result was perturbed following subcutaneous transplantation. The tumors formed in the mammary fat pads exhibited immune reactivities to prolactin receptor, progesterone receptor, green florescent protein, Ki67, CD44, estrogen receptor alpha/beta and cytokeratin 8, while all of the tumors and their derived primary cells exhibited immunoreactivity to estrogen receptor alpha/beta and cytokeratin 8. Cancer stem cells can be developed from pluripotent stem cells via the secretory factors of cancer-derived cells with the capacity to inherit tissue specificity. However, cancer stem cells should be plastic enough to be affected by the microenvironment of specific tissues. In summary, we successfully established a breast cancer tumor model using mouse induced pluripotent stem cells developed from normal fibroblasts without genetic manipulation

Hematopoietic Cells Derived from Cancer Stem Cells Generated from Mouse Induced Pluripotent Stem Cells

Cancer stem cells (CSCs) represent the subpopulation of cancer cells with the ability to differentiate into other cell phenotypes and initiated tumorigenesis. Previously, we reported generating CSCs from mouse induced pluripotent stem cells (miPSCs). Here, we investigated the ability of the CSCs to differentiate into hematopoietic cells. First, the primary cells were isolated from malignant tumors that were formed by the CSCs. Non-adherent cells (NACs) that arose from adherent cells were collected and their viability, as well as the morphology and expression of hematopoietic cell markers, were analyzed. Moreover, NACs were injected into the tail vein of busulfan conditioned Balb/c nude mice. Finally, CSCs were induced to differentiate to macrophages while using IL3 and SCF. The round nucleated NACs were found to be viable, positive for hematopoietic lineage markers and CD34, and expressed hematopoietic markers, just like homing to the bone marrow. When NACs were injected into mice, Wright-Giemsa staining showed that the number of white blood cells got higher than those in the control mice after four weeks. CSCs also showed the ability to differentiate toward macrophages. CSCs were demonstrated to have the potential to provide progenies with hematopoietic markers, morphology, and homing ability to the bone marrow, which could give new insight into the tumor microenvironment according to the plasticity of CSCs