SYNTHESIS AND BIOLOGICAL EVALUATION OF SECOND GENERATION ANIBAMINE ANALOGUES AS NOVEL ANTI-PROSTATE CANCER AGENTS

Prostate cancer is the most prevalent non-cutaneous cancer among men. Since the 19th century when Virchow first introduced the concept of inflammation in cancer, chemokines and their receptors have garnered a lot of interest. Chemokine receptor CCR5 has been especially implicated in many disease states and recently found to be over expressed in prostate cancer cell lines. Anibamine, a natural CCR5 antagonist discovered in 2004, has been found to have significant anti-prostate cancer activity at micromolar level. To optimize this compound and also discover a novel pharmacophore, exploration of the original structure was carried out. Significant modifications were made to the side chain in the original structure and ten different analogues were prepared by altering the original synthetic route. While cytotoxicity assay proved the compounds to be non toxic to normal cells, anti-proliferation assay displayed that having a bulky, hydrophobic group in the side chain of the parent compound is essential for the activity. Looking at this data, the third generation of analogues can be prepared that might generate a better lead compound for the treatment of prostate cancer

Cannabidiol alters the immune response to Porphyromonas gingivalis in mice.

Background: Porphyromonas gingivalis is an important etiologic agent of chronic periodontitis, an infectious disease defined by destruction of supporting tissues of the teeth. Marijuana is a risk factor for chronic periodontitis, although underlying mechanisms are poorly understood. As phytocannabinoids have been ascribed antiinflammatory properties, we hypothesized that cannabidiol exposure would lead to altered immune response to P. gingivalis infection facilitating bacterial persistence and, subsequently, increased alveolar bone loss in cannabidiol (CBD)-exposed mice. Methods: P. gingivalis-infected cannabinoid receptor 2 (CB2) knockout and wild type C57/Bl6 mice were exposed, or not exposed, to cannabidiol. Oral swabs from mice were used to monitor the presence of P. gingivalis by PCR and culture. Skulls were harvested, defleshed and stained to analyze the amount of bone loss under microscope. Alveolar bone volume and alveolar bone density were also analyzed by using CT. Systemic P. gingivalis-specific and total IgG and IgM antibodies were quantified by ELISA. Periodontal expression of inflammatory markers – CD14, CD45, MIP-2, MMP-9 and IL-1β was measured in the maxillary gingivae by qPCR. Results: In our hands oral gavage model appears to be one of repeated transient infection with P. gingivalis rather than a persistent colonization model. Although P. gingivalis could not be detected in oral swabs, the infection was sufficient to produce an immune reaction in gingiva and serum. Cannabidiol suppresses total IgM production in mice. If this occurs in humans, it applies that adaptive immune response is less well equipped for the arrival of oral pathogens. However, CBD did not affect P. gingivalis specific IgG response. CBD significantly reduced the expression of IL-1β, CD45 and CD14 inflammatory markers in maxillary gingiva in P. gingivalis infected wild type mice but not CB2 -/- mice. Deficient immune response to P. gingivalis may lead to its persistence and more severe periodontal destruction in cannabis users. This is analogous with in-vitro nicotine studies and with clinical studies showing more severe clinical manifestations of chronic periodontitis in tobacco smokers. However, our results showed a reduction in MMP-9 expression in presence of cannabidiol. This anomaly is hard to explain and does not correspond with the findings in cigarette smokers where MMP-9 levels are significantly higher. Increased bone loss was hypothesized because we know cannabis drives bone loss in animals and humans. This did not happen here. May be because we didn’t have persistent infection. However, immune differences between wild type versus knock out mice suggest that we could see a long-term effect in chronic infection. Conclusion and Practical Implications: The results show that cannabidiol alters the immune response of mice infected by P. gingivalis. Further studies aimed at understanding the effects of altered immune response in presence of cannabidiol should be performed. This is particularly important as prevalence of cannabis smoking is currently on the rise, partly due to legalization or decriminalization in increasing jurisdictions. Keywords - Alveolar bone loss, Cannabidiol, CB2, Periodontitis, Phytocannabinoids, Porphyromonas gingivali

Characterization of Glyphosate-Resistant Amaranthus Palmeri (Palmer Amaranth) Tolerance to ALS- and HPPD-Inhibiting Herbicides

Palmer amaranth is a principal weed problem across the United States and is resistant to several herbicide modes of action. By 2008, Palmer amaranth in Arkansas was reported to be resistant to both ALS- and EPSPS-inhibitors, but the predominant resistance mechanisms are yet to be explored. Herbicide options with different modes of action are needed to provide effective Palmer amaranth control and HPPD-inhibitors (e.g. mesotrione) are among these. The goal of this research was to elucidate the resistance profile of Palmer amaranth in Arkansas to ALS herbicides and glyphosate (EPSPS-inhibitor) as well as evaluate the differential tolerance of Palmer amaranth to mesotrione. This research aimed to (1) evaluate the response of Palmer amaranth populations to the full dose of glyphosate and mesotrione; (2) determine if tolerance to mesotrione is heritable; (3) determine the mechanism of resistance to glyphosate in selected accessions; and (4) verify the target-site as the mechanism of resistance in ALS-resistant Palmer amaranth. For objective 1, a total of 119 accessions were collected from crop fields in Arkansas between 2008 and 2014. Overall, 55% of the accessions (115) were glyphosate-resistant (GR). Mesotrione controlled 74% of the accessions (119); the remaining accessions had survivors with high injury (61%-90%). For objective 2, low level of tolerance to mesotrione (3- to 5-fold) was observed in four recalcitrant accessions. For objective 3, 20 accessions were selected. GR accessions had ED50 494 g ha-1 to 1355 g ha-1 and for susceptible accessions ED50 ranged from 28 g ha-1 to 207 g ha-1. EPSPS gene amplification was the primary mechanism of resistance. For objective 4, Palmer amaranth accessions were cross-resistant to pyrithiobac and trifloxysulfuron. Out of 20 accessions, 19 showed 21- to 56-fold resistance to trifloxysulfuron than the susceptible. Four and seven increased ALS copies were observed in a single plant from White and Mississippi counties, respectively, indicating the elevated ALS copies as potential mechanism of resistance in these accessions. Although, all accessions but susceptible had Trp574Ser mutation along with Ala122Thr, Pro197Ala and Ser653Asn present in a few plants, confirming mutations at the target-site as the main mechanism of resistance to ALS-inhibitors

Assessment of study among radiography students about how to take informed consent

Background: Consent form is an integral first step before any radiological procedure that engages methods that can be threatening to patients. Future radiographers i.e., radiography students should have sufficient and appropriate knowledge regarding obtaining an informed consent. The aim of my study is to evaluate and assess the knowledge and impart the importance of informed consent form among Radiography students under various conditions.Methods: A questionnaire based retrospective cross-sectional was used to assess the knowledge of informed consent among radiographic students. The study was carried out in radiology department of Maharishi Markandeshwar University. The questionnaire comprised of self-structured MCQs questionnaire consisted of demographic data and basic questions regarding informed consent.Results: Out of 156 undergraduate and postgraduate radiology paramedical students, 87 took part in the study. It was assessed how much information radiography students possess on taking informed consent. The gender ratio was allocated into 2 groups. First group was female consisting of 45 (51.72%) number of participants and second group male consisting of 42 (48.28%) number of students with mean of 21 years.Conclusions: Indulging on the subject of consent form, almost all of the students understood the concept of consent form or had heard about the concept of informed consent to some extent. Maximum students were in favour of classes being held discussing consent form. The statistical data of all participants who gave the correct answer is 81.20%, indicating that radiography students understand and grasp the concept of consent very well

Knowledge and perception of magnetic resonance imaging safety among patients

Background: MRI knowledge and safety are very important not for only MRI technicians, doctors, professionals but also for patients who are undergoing MRI examination.  The key purpose of this research to evaluate the knowledge and perception of MRI Safety among patients, as accidents can happen due to patient’s insufficient knowledge regarding MRI. Method: The retrospective study was performed around 50 patients at Maharishi Markandeshwar institute of medical sciences and research, Ambala, Haryana. Questionnaire design was used to assess their knowledge and perception. The questionnaire form was filled by an investigator directly discussion with patients and the data was collected and analyzed using Microsoft excel sheet. Result: It was assessed that how much knowledge and what is the perception of MRI study among patients. There were 23 (46%) female and f 27 (54%) male in different age group. In response to question regarding how patients felt before MRI scan, 16% patients felt panic, 10% sensed fear and panic, fear and anxiety were experienced by 6% patients, fear was the emotion that 15 patients (30%) suffered, anxiety as the sole was felt by 7 (14%), for 2 (4%) regret was the sensation and 10 patients (20%) didn’t have any issue. Conclusions: The conclusion of this research depicted that majority of the patients were in dark with relation to the knowledge and perception of MRI. It is crucial to explain to the patients about the contraindications and rules regarding the MRI scan

Perceptions of Indian Women Toward A Deserted Woman

Marriage is a sacred and essential ritual of Indian society.The failure of a marriage is devastating to both parties, especially a woman suffers from intense feelings of anxiety, guilt, anger, depression and low self-confidence after separation. Indian women in particular makepost-desertion experiences more complicate as they are the worst critic of the divorcee/deserted woman in social periphery. Indian women look upon a divorcee /deserted woman in a pseudo-superiority complex that they have been able to maintain their matrimonial relation whereas particular divorcee/deserted woman has failed. It is tough enough to survive as a woman in patriarchal society of India, so a change in mindset of the Indian women is required to let divorcee/deserted women breathe freely get their respectful place in developing society

Ageing Process and Physiological Changes

Ageing is a natural process. Everyone must undergo this phase of life at his or her own time and pace. In the broader sense, ageing reflects all the changes taking place over the course of life. These changes start from birth—one grows, develops and attains maturity. To the young, ageing is exciting. Middle age is the time when people notice the age-related changes like greying of hair, wrinkled skin and a fair amount of physical decline. Even the healthiest, aesthetically fit cannot escape these changes. Slow and steady physical impairment and functional disability are noticed resulting in increased dependency in the period of old age. According to World Health Organization, ageing is a course of biological reality which starts at conception and ends with death. It has its own dynamics, much beyond human control. However, this process of ageing is also subject to the constructions by which each society makes sense of old age. In most of the developed countries, the age of 60 is considered equivalent to retirement age and it is said to be the beginning of old age. In this chapter, you understand the details of ageing processes and associated physiological changes

Anaemia in pregnancy: prevalence and treatment response to various modalities: a prospective study

Background: Anaemia seen in pregnancy are largely preventable and easily treatable if detected in time, despite this, anaemia still continues to be a common cause of maternal and perinatal morbidity and mortality in India.Methods: A prospective observational study of 200 pregnant women with anaemia was carried out from Jun 2017 to December 2018 at a Tertiary care hospital with pan India population. Patients underwent clinical examination and laboratory tests to find out the severity and type of anaemia and were treated accordingly. Iron deficiency anaemia was treated with oral or intravenous iron therapy depending upon the hemoglobin concentration. Patients were followed up after 28 days of treatment and hemoglobin estimation was done to monitor the treatment response.Results: A total 36.49% pregnant women had hemoglobin less than 10 gm%. 151 out of 200 women had serum ferritin <12 ng/ml which indicates that iron deficiency anaemia is the commonest type of anaemia in pregnancy. Overall, out of 200 patients 5.5% patients were found to have hemoglobinopathies (β thalassemia trait). After 28 days of treatment mean increase in hemoglobin was 2.40 gm% and 4.24 gm% in patients receiving oral and intravenous iron therapy respectively.Conclusions: A total 36.49% pregnant women were found to have anaemia during pregnancy and iron deficiency anaemia is the commonest type of anaemia. Therefore, there is still a need for dietary counselling and health education in the community. 5.5% patients were found to have beta thalassemia trait which was detected only after conducting hemoglobin electrophoresis. Both oral and intravenous iron therapy are effective in treatment of iron deficiency anaemia but intravenous iron therapy results in a more rapid resolution of anaemia

Two-temperature accretion flows around strongly magnetized stars and their spectral analysis

We investigate two-temperature accretion flows onto strongly magnetized compact stars. Matter is accreted in the form of an accretion disc upto the disc radius ($r_{\rm d}$), where, the magnetic pressure exceeds both the gas and ram pressure and thereafter the matter is channelled along the field lines onto the poles. We solve the equations of motion self-consistently along the field lines, incorporating radiative processes like bremsstrahlung, synchrotron and inverse-Comptonization. For a given set of constants of motion, the equations of motion do not produce unique transonic solution. Following the second law of thermodynamics the solution with the highest entropy is selected and thereby eliminating the degeneracy in solution. We study the properties of these solutions and obtain corresponding spectra as a function of the magnetic field ($B_*$), spin period ($P$) and accretion rate of the star ($\dot{M}$). A primary shock is always formed just near the surface. The enhanced radiative processes in this post-shock region slows down the matter and it finally settles on the surface of the star. This post-shock region contributes to $\gtrsim 99.99\%$ of the total luminosity obtained from the accretion flow. It is still important to study the full accretion flow because secondary shocks may be present for some combination of $B_*$, $P$ and ${\dot{M}}$ in addition to primary shocks. We find that secondary shocks, if present, produce an extended emission at higher energies in the spectra.Comment: 18 pages, 17 figures and accepted for publication in MNRA