Oral vitamin B(12 )therapy in the primary care setting: a qualitative and quantitative study of patient perspectives

BACKGROUND: Although oral replacement with high doses of vitamin B(12 )is both effective and safe for the treatment of B(12 )deficiency, little is known about patients' views concerning the acceptability and effectiveness of oral B(12). We investigated patient perspectives on switching from injection to oral B(12 )therapy. METHODS: This study involved a quantitative arm using questionnaires and a qualitative arm using semi-structured interviews, both to assess patient views on injection and oral therapy. Patients were also offered a six-month trial of oral B(12 )therapy. One hundred and thirty-three patients who receive regular B(12 )injections were included from three family practice units (two hospital-based academic clinics and one community health centre clinic) in Toronto. RESULTS: Seventy-three percent (63/86) of respondents were willing to try oral B(12). In a multivariate analysis, patient factors associated with a "willingness to switch" to oral B(12 )included being able to get to the clinic in less than 30 minutes (OR 9.3, 95% CI 2.2–40.0), and believing that frequent visits to the health care provider (OR 5.4, 95% CI 1.1–26.6) or the increased costs to the health care system (OR 16.7, 95% CI 1.5–184.2) were disadvantages of injection B(12). Fifty-five patients attempted oral therapy and 52 patients returned the final questionnaire. Of those who tried oral therapy, 76% (39/51) were satisfied and 71% (39/55) wished to permanently switch. Factors associated with permanently switching to oral therapy included believing that the frequent visits to the health care provider (OR 35.4, 95% CI 2.9–432.7) and travel/parking costs (OR 8.7, 95% CI 1.2–65.3) were disadvantages of injection B(12). Interview participants consistently cited convenience as an advantage of oral therapy. CONCLUSION: Switching patients from injection to oral B(12 )is both feasible and acceptable to patients. Oral B(12 )supplementation is well received largely due to increased convenience. Clinicians should offer oral B(12 )therapy to their patients who are currently receiving injections, and newly diagnosed B(12)-deficient patients who can tolerate and are compliant with oral medications should be offered oral supplementation

The interplay between endoplasmic reticulum stress and inflammation

Endoplasmic reticulum (ER) stress may be both a trigger and consequence of chronic inflammation. Chronic inflammation is often associated with diseases that arise because of primary misfolding mutations and ER stress. Similarly, ER stress and activation of the unfolded protein response (UPR) is a feature of many chronic inflammatory and autoimmune diseases. In this review, we describe how protein misfolding and the UPR trigger inflammation, how environmental ER stressors affect antigen presenting cells and immune effector cells, and present evidence that inflammatory factors exacerbate protein misfolding and ER stress. Examples from both animal models of disease and human diseases are used to illustrate the complex interactions between ER stress and inflammation, and opportunities for therapeutic targeting are discussed. Finally, recommendations are made for future research with respect to the interaction of ER stress and inflammation

ER stress and the unfolded protein response in intestinal inflammation

Although there have been advances in our understanding of carcinogenesis and development of new treatments, cancer remains a common cause of death. Many regulatory pathways are incompletely understood in cancer development and progression, with a prime example being those related to the endoplasmic reticulum (ER). The pathological sequelae that arise from disruption of ER homeostasis are not well defined. The ER is an organelle that is responsible for secretory protein biosynthesis and the quality control of protein folding. The ER triggers an unfolded protein response (UPR) when misfolded proteins accumulate, and while the UPR acts to restore protein folding and ER homeostasis, this response can work as a switch to determine the death or survival of cells. The treatment of cancer with agents that target the UPR has shown promising outcomes. The UPR has wide crosstalk with other signaling pathways. Multi-targeted cancer therapies which target the intersections within signaling networks have shown synergistic tumoricidal effects. In the present review, the basic cellular and signaling pathways of the ER and UPR are introduced; then the crosstalk between the ER and other signaling pathways is summarized; and ultimately, the evidence that the UPR is a potential target for cancer therapy is discussed. Regulation of the UPR downstream signaling is a common therapeutic target for different tumor types. Tumoricidal effects achieved from modulating the UPR downstream signaling could be enhanced by phosphodiesterase 5 (PDE5) inhibitors. Largely untapped by Western medicine for cancer therapies are Chinese herbal medicines. This review explores and discusses the value of some Chinese herbal extracts as PDE5 inhibitors