Background6-Shogaol is one of the major compounds in the ginger rhizome that may contribute to its anti-inflammatory properties. Confirmation of this contribution was sought in this study in Sprague- Dawley rats (200–250 g) treated with a single injection (0.5 ml of 1 mg/ml) of a commercial preparation of complete Freund's Adjuvant (CFA) to induce monoarthritis in the right knee over a period of 28 days. During this development of arthritis, each rat received a daily oral dose of either peanut oil (0.2 ml-control) or 6-shogaol (6.2 mg/Kg in 0.2 ml peanut oil).ResultsWithin 2 days of CFA injection, the control group produced maximum edematous swelling of the knee that was sustained up to the end of the investigation period. But, in the 6-shogaol treated group, significantly lower magnitudes of unsustained swelling of the knees (from 5.1 ± 0.2 mm to 1.0 ± 0.2 mm, p < 0.002, n = 6) were produced during the investigation period. Unsustained swelling of the knees (from 3.2 ± 0.6 mm to 0.8 ± 1.1 mm, p < 0.00008, n = 6) was also produced after 3 days of treatment with indomethacin (2 mg/Kg/day) as a standard anti-inflammatory drug, but during the first 2 days of drug treatment swelling of the knees was significantly larger (11.6 ± 2.0 mm, p < 0.0002, n = 6) than either the controls or the 6-shogaol treated group of rats. This exaggerated effect in the early stage of indomethacin treatment was inhibited by montelukast, a cysteinyl leukotriene receptor antagonist. Also, 6-shogaol and indomethacin were most effective in reducing swelling of the knees on day 28 when the controls still had maximum swelling. The effect of 6-shogaol compared to the controls was associated with significantly lower concentration of soluble vascular cell adhesion molecule-1 (VCAM-1) in the blood and infiltration of leukocytes, including lymphocytes and monocytes/macrophages, into the synovial cavity of the knee. There was also preservation of the morphological integrity of the cartilage lining the femur compared to damage to this tissue in the peanut oil treated control group of rats.ConclusionFrom these results, it is concluded that 6-shogaol reduced the inflammatory response and protected the femoral cartilage from damage produced in a CFA monoarthritic model of the knee joint of rats.
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase, which is an essential player in regulating cell migration, invasion, adhesion, proliferation, and survival. Its overexpression and activation have been identified in sixty-eight percent of epithelial ovarian cancer patients and this is significantly associated with higher tumor stage, metastasis, and shorter overall survival of these patients. Most recently, a new role has emerged for FAK in promoting resistance to taxane and platinum based therapy in ovarian and other cancers. The development of resistance is a complex network of molecular processes that makes the identification of a targetable biomarker in platinum and taxane resistant ovarian cancer a major challenge. FAK overexpression upregulates ALDH and XIAP activity in platinum-resistant and increases CD44, YB1, and MDR-1 activity in taxane-resistant tumors. FAK is therefore now emerging as a prognostically significant candidate in this regard, with mounting evidence from recent successes in preclinical and clinical trials using small molecule FAK inhibitors. This review will summarize the significance and function of FAK in ovarian cancer, and its emerging role in chemotherapeutic resistance. We will discuss the current status of FAK inhibitors in ovarian cancers, their therapeutic competencies and limitations, and further propose that the combination of FAK inhibitors with platinum and taxane-based therapies could be an efficacious approach in chemotherapeutic resistant disease.
c-kit is a classical proto-oncogene that encodes a receptor tyrosine kinase (RTK) that responds to stem cell factor (SCF). C-KIT signaling is a critical regulator of cell proliferation, survival, and migration and is implicated in several physiological processes, including pigmentation, hematopoiesis and gut movement. Accumulating evidence suggests that dysregulated c-KIT function, caused by either overexpression or mutations in c-kit, promotes tumor development and progression in various human cancers. In this review, we discuss the most important structural and biological features of c-KIT, as well as insights into the activation of intracellular signaling pathways following SCF binding to this RTK. We then illustrate how different c-kit alterations are associated with specific human cancers and describe recent studies that highlight the contribution of c-KIT to cancer stemness, epithelial-mesenchymal transition and progression to metastatic disease in different experimental models. The impact of tyrosine kinase inhibitors in treating c-KIT-positive tumors and limitations due to their propensity to develop drug resistance are summarized. Finally, we appraise the potential of novel therapeutic approaches targeting c-KIT more selectively while minimizing toxicity to normal tissue.
Background: Lesbian, gay, bisexual, and transgender (LGBT) seniors are generally a medically underserved population that faces unique healthcare challenges. When compared to younger patients, LGBT seniors are at a greater risk for social isolation and have higher rates of smoking, disability, physical and mental distress, and lack of access to healthcare services. They are often reluctant to discuss their sexual orientations and gender identities with healthcare providers due to fear of discrimination and receiving inferior care based on prior unsatisfactory experiences with untrained or insensitive healthcare providers. Furthermore, recent research has revealed that only about 50% of primary care providers indicated confidence in providing culturally competent LGBT healthcare, highlighting the need for more LGBT proficiency training in medical school curricula.
Objectives: The aim of this study was to provide early intervention training to first-year medical students regarding best practices for equitable healthcare for LGBT seniors through integrative, small group, case-based discussions. The impact of this activity on the knowledge and attitudes of medical students regarding LGBT healthcare was also assessed.
Methods: First-year medical students participated in a two-hour small group, case-based discussion. Each group consisted of seven to eight students with one of seven facilitators who were invited members of the LGBT community. Students were provided with two clinical case scenarios related to treatment of LGBT senior patients. Students were given a pre/post-session knowledge and attitude survey to assess the impact of the session on their attitudes and understanding of the importance of providing equitable healthcare to LGBT patients. A rubric was also used by facilitators to evaluate level of student engagement and professionalism.
Results: A total of 51 first-year medical students attended the session and 38 (74.5%) completed the pre/post surveys. There was diverse representation in our student demographic with 5.2% of respondents identifying as LGBT. Survey results showed a significant increase in knowledge confidence and attitudes following the session. Students’ attitudes regarding determinants of health status changed significantly for nine of the 13 (69%) survey items. In addition, their confidence in knowledge regarding healthcare barriers, health issues, and practices for LGBT culturally competent care significantly increased post-session. Data from our assessment rubrics also show that students were highly professional and engaged with the LGBT facilitators.
Conclusion: Our study provides some evidence that case-based training of medical students regarding issues that affect health of LGBT seniors can improve attitudes and sensitize them to the unique needs of this population. Through this activity, the students indicated their desire to learn more about the topics covered and to receive further training in this field of study. While the study wa...
A crude extract of the leaves Justicia pectoralis reduced the formation of histamine-induced wheals in sensitized guinea pigs (p < 0.05) and also reduced histamine-induced tracheal smooth muscle contractions (p < 0.05). It blocked the effect of contraction produced by histamine in the airways; this property supports folklore claims for its use as an antihistamine.
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