A COMPREHENSIVE AYURVEDIC MANAGEMENT OF PERIPHERAL VASCULAR DISEASE – A CASE REPORT

Vatarakta, classified as a Mahavatavyadhi and as a separate disease in the scriptures has evoked attention of the Ayurvedic physicians and scholars because of its versatility in symptoms. Focussing on a single disease elaborated in modern science and equate it to Vatarakta cannot be considered as an apt methodology. Rather, Vatarakta can be understood as a conglomeration of different diseases such as autoimmune disorders, peripheral arterial disease and gouty arthritis to name a few. In this case study, a 42 year old male patient diagnosed with peripheral vascular disease was treated with the aid of the principles of Vataraktachikitsa and medications suitable to the disease under consideration. Shamana modality of treatment was advocated for the patient. The findings were obtained with timely monitoring of the symptoms and condition of the disease. Medications which included Shilajatu, Guggulu tiktakakashaya and Jatyaditaila provided significant relief

A comparison of 64Cu-labeled bi-terminally PEGylated A20FMDV2 peptides targeting integrin ανβ6

Expression of epithelial-specific integrin

Attitude towards drug adherence in inpatients with bipolar affective disorder: a cross-sectional study

Background and Objectives: Bipolar Affective Disorder is the sixth leading cause of disability-adjusted life years in individuals aged 15-44 years. Among the patients with Bipolar Disorder, about 60% are at least partially non-adherent to medications. This study attempted to study attitude towards drug adherence in inpatients with bipolar affective disorder. Materials and Methods: Consecutive patients, between 18 to 60 years of age, diagnosed with Bipolar Affective Disorder, undergoing inpatient treatment over a two-month period, were recruited. Their attitude towards drug adherence was assessed using a 30-item version of the Drug Attitude Inventory (DAI). Results: Subjects in this study had good medication adherence (DAI= 3.12± 7.09), indicating these patients tended to report favourable views towards their psychiatric medications. Conclusion: Assessment of attitude towards non-adherence in this population showed good medication adherence and a positive response to treatment

Preclinical efficacy of a PARP-1 targeted Auger-emitting radionuclide in prostate cancer

There is an unmet need for better therapeutic strategies for advanced prostate cancer. Poly (ADP-ribose) polymerase-1 (PARP-1) is a chromatin-binding DNA repair enzyme overexpressed in prostate cancer. This study evaluates whether PARP-1, on account of its proximity to the cell\u27s DNA, would be a good target for delivering high-linear energy transfer Auger radiation to induce lethal DNA damage in prostate cancer cells. We analyzed the correlation between PARP-1 expression and Gleason score in a prostate cancer tissue microarray. A radio-brominated Auger emitting inhibitor (

Pomegranate Fruit as a Rich Source of Biologically Active Compounds

Pomegranate is a widely used plant having medicinal properties. In this review, we have mainly focused on the already published data from our laboratory pertaining to the effect of methanol extract of pericarp of pomegranate (PME) and have compared it with other relevant literatures on Punica. Earlier, we had shown its antiproliferative effect using human breast (MCF-7, MDA MB-231), and endometrial (HEC-1A), cervical (SiHa, HeLa), and ovarian (SKOV3) cancer cell lines, and normal breast fibroblasts (MCF-10A) at concentration of 20–320 μg/mL. The expressions of selected estrogen responsive genes (PR, pS2, and C-Myc) were downregulated by PME. Unlike estradiol, PME did not increase the uterine weight and proliferation in bilaterally ovariectomized Swiss-Albino mice models and its cardioprotective effects were comparable to that of 17β-estradiol. We had further assessed the protective role of PME on skeletal system, using MC3T3-E1 cells. The results indicated that PME (80 μg/mL) significantly increased ALP (Alkaline Phosphatase) activity, supporting its suggested role in modulating osteoblastic cell differentiation. The antiosteoporotic potential of PME was also evaluated in ovariectomized (OVX) rodent model. The results from our studies and from various other studies support the fact that pomegranate fruit is indeed a source of biologically active compounds

Generation of a Live-Attenuated Strain of Chikungunya Virus from an Indian Isolate for Vaccine Development

Chikungunya virus (CHIKV) re-emergence in the last decade has resulted in explosive epidemics. Along with the classical symptoms of fever and debilitating arthralgia, there were occurrences of unusual clinical presentations such as neurovirulence and mortality. These generated a renewed global interest to develop prophylactic vaccines. Here, using the classical approach of virus attenuation, we developed an attenuated CHIKV strain (RGCB355/KL08-p75) for the purpose. Repeated passaging (75 times) of a local clinical isolate of ECSA lineage virus in U-87 MG human astrocytoma cells, an interferon-response-deficient cell line, resulted in efficient adaptation and attenuation. While experimental infection of 3-day old CHIKV-susceptible BALB/c pups with the parent strain RGCB355/KL08-p4 resulted in death of all the animals, there was 100% survival in mice infected with the attenuated p75. In adult, immunocompetent, CHIKV-non-susceptible C57BL/6 mice, inoculation with p75 induced high antibody response without any signs of disease. Both p4 and p75 strains are uniformly lethal to interferon-response-deficient AG129 mice. Passive protection studies in AG129 mice using immune serum against p75 resulted in complete survival. Whole-genome sequencing identified novel mutations that might be responsible for virus attenuation. Our results establish the usefulness of RGCB355/KL08-p75 as a strain for vaccine development against chikungunya

Therapeutic Efficacy of ¹⁷⁷Lu-Labeled A20FMDV2 Peptides Targeting α_νβ₆

Integrin ανβ6 promotes migration and invasion of cancer cells, and its overexpression often correlates with poor survival. Therefore, targeting ανβ6 with radioactive peptides would be beneficial for cancer imaging and therapy. Previous studies have successfully developed radiotracers based on the peptide A20FMDV2 that showed good binding specificity for ανβ6. However, one concern of these ανβ6 integrin-targeting probes is that their rapid blood clearance and low tumor uptake would preclude them from being used for therapeutic purposes. In this study, albumin binders were used to increase tumor uptake for therapeutic applications while the non-albumin peptide was evaluated as a potential positron emission tomography (PET) imaging agent. All peptides used the DOTA chelator for radiolabeling with either 68Ga for imaging or 177Lu for therapy. PET imaging with [68Ga]Ga-DOTA-(PEG28)2-A20FMDV2 revealed specific tumor uptake in ανβ6-positive tumors. Albumin-binding peptides EB-DOTA-(PEG28)2-A20FMDV2 and IBA-DOTA-(PEG28)2-A20FMDV2 were radiolabeled with 177Lu. Biodistribution studies in normal mice showed longer blood circulation times for the albumin binding peptides compared to the non-albumin peptide. Therapy studies in mice demonstrated that both 177Lu-labeled albumin binding peptides resulted in significant tumor growth inhibition. We believe these are the first studies to demonstrate the therapeutic efficacy of a radiolabeled peptide targeting an ανβ6-positive tumor

The estrogen receptor alpha nuclear localization sequence is critical for fulvestrant-induced degradation of the receptor

Fulvestrant, a selective estrogen receptor down-regulator (SERD) is a pure competitive antagonist of estrogen receptor alpha (ERα). Fulvestrant binds ERα and reduces the receptor's half-life by increasing protein turnover, however, its mechanism of action is not fully understood. In this study, we show that removal of the ERα nuclear localization sequence (ERδNLS) resulted in a predominantly cytoplasmic ERα that was degraded in response to 17-β-estradiol (E2) but was resistant to degradation by fulvestrant. ERδNLS bound the ligands and exhibited receptor interaction similar to ERα, indicating that the lack of degradation was not due to disruption of these processes. Forcing ERδNLS into the nucleus with a heterologous SV40-NLS did not restore degradation, suggesting that the NLS domain itself, and not merely receptor localization, is critical for fulvestrant-induced ERα degradation. Indeed, cloning of the endogenous ERα NLS onto the N-terminus of ERδNLS significantly restored both its nuclear localization and turnover in response to fulvestrant. Moreover, mutation of the sumoylation targets K266 and K268 within the NLS impaired fulvestrant-induced ERα degradation. In conclusion, our study provides evidence for the unique role of the ERα NLS in fulvestrant-induced degradation of the receptor.Fil: Casa, Angelo J.. Baylor College of Medicine; Estados UnidosFil: Hochbaum, Daniel. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sreekumar, Sreeja. University of Pittsburgh; Estados UnidosFil: Oesterreich, Steffi. University of Pittsburgh; Estados UnidosFil: Lee, Adrian V.. University of Pittsburgh; Estados Unido

Progesterone regulates the proliferation of breast cancer cells – in vitro evidence

Juberiya M Azeez,1 Hima Sithul,1 Indhu Hariharan,1 Sreeja Sreekumar,1 Jem Prabhakar,2 Sreeharshan Sreeja,1 Madhavan Radhakrishna Pillai1 1Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, 2Division of Surgical Oncology, Regional Cancer Centre, Thiruvananthapuram, India Abstract: Reports state that surgery performed at different phases of the menstrual cycle may significantly affect breast cancer treatment outcome. From previous studies, we identified differentially expressed genes in each menstrual cycle phase by microarray, then subjected them to functional in vitro analyses. Microarray studies disclosed genes that are upregulated in the luteal phase and follicular phase. TOB-1 is a tumor suppressor gene and was expressed exclusively in the luteal phase in our microarray study. Therefore, we further functionally characterized the protein product of TOB-1 in vitro. To our knowledge, no studies have yet been conducted on reactive oxygen species-regulated tumor suppressor interactions in accordance with the biphasic nature of progesterone. This work demonstrates that progesterone can produce reactive oxygen species in MCF-7 cells and that TOB-1 exerts a series of non-genomic interactions that regulate antiproliferative activity by modulating the antioxidant enzyme superoxide dismutase. Furthermore, this study implicates PTEN as an interacting partner for TOB-1, which may regulate the downstream expression of cell cycle control protein p27 via multiple downstream signaling pathways of progesterone through a progesterone receptor, purely in a time- and concentration-dependent manner. These results support the hypothesis that surgery conducted during the luteal phase of the menstrual cycle may facilitate improved patient survival. Keywords: progesterone, reactive oxygen species, TOB-1, cell growth arres