Cholesterol Feeding and Gallbladder Muscle Contractility
William J. Snape, Stephen M. Collins in Effects of Immune Cells and Inflammation on Smooth Muscle and Enteric Nerves, 2020
We and others have tested the hypothesis that contact of altered bile with the gallbladder mucosa, not the systemic effects, results in reduced contractility. Fridhandler et al.10 and we found that intestinal muscle is not altered by cholesterol feeding.13 The maximal contractile force in response to carbachol, potassium, and calcium (in chemically skinned muscle) was not altered. Furthermore, one of the biochemical steps leading up to contraction, myosin light chain-20 phosphorylation also was not altered. If systemic effects were involved, one might expect changes in intestinal muscle as well. This was not seen. We recently tested the hypothesis another way. If contact with altered bile is the mechanism, then limiting contact should prevent the reduced contractility and formation of stones. Prairie dogs were surgically prepared to divert bile around the gallbladder.14 Another group underwent sphincterotomy, a procedure shown to reduce bile storage in the gallbladder and to prevent stone formation. Each group was further divided so that some animals were fed cholesterol diet and some were fed control diet. After 8 days, gallbladder muscle contractility was determined. Cholesterol feeding had no effect on contractility in those animals with bile diversion. Also, little to no bile and no stones were found in any of their gallbladders. Thus, these studies suggest that the abnormal bile induced by cholesterol feeding must come into contact with the gallbladder mucosa in order to affect function. This indicates a local rather than a systemic effect.
Regulatory Issues in Drug Delivery to the Eye
Glenn J. Jaffe, Paul Ashton, P. Andrew Pearson in Intraocular Drug Delivery, 2006
A number of the drug delivery systems deliver medications for a very long period of time; sometimes over a number of years. Rather than launching into large, expensive, and resource-consuming trials with implants that deliver the drug for many years, it is often prudent to prove that the drug is effective over a shorter period of time. Although an implant can be filled with drug and deliver the compound for several years, it may make sense to start studies with implants that last for less time. Similarly, this will also demonstrate that the drug is active when administered to a specific location. For example, just because a drug works when delivered systemically does not mean that it will work equally as well if the drug is delivered into the vitreous, even if similar intravitreal levels are achieved with both systemic and intravitreal drug delivery. Some drugs may have a systemic effect contributing to their efficacy. For other drugs, drug levels at the level of the retinal pigment epithelium (RPE) may be more important than intravitreal drug levels.
Skin Aging Clock and Its Resetting by Light-Emitting Diode Low-Level Light Therapy
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
First of all, LED-LLLT works at the systemic level benefiting areas of the body not directly targeted. This has been well demonstrated, particularly in a study on the indirect healing of standardized burns in the rat and mouse model using the systemic effect [56]. On post-burn day 7, all of the indirectly irradiated wounds were at least 70% healed, and some 40% were fully healed compared with the control wounds. It is believed that photoproducts created by light–cell interaction in the irradiated tissue are carried by the vascular or lymphatic system throughout the body, thereby accelerating the healing of the wounds in the treated animals even though they were not directly irradiated. The blood vascular system is another good candidate for the systemic effect. In a study on the axial pattern flap in the rat model, treatment group animals were treated with 830 nm LLLT aimed at the iliolumbar feeder artery for the flap, while control animals were treated in exactly the same way but without actual irradiation [57]. At 90 min after a single treatment, speckle Doppler flowmetry showed increased full-flap perfusion in the treated animals but not in the control animals, which was matched by statistically significantly better flap survival in the treated group.
Cytokine storm associated coagulation complications in COVID-19 patients: Pathogenesis and Management
Published in Expert Review of Anti-infective Therapy, 2021
Shreya R. Savla, Kedar S. Prabhavalkar, Lokesh K. Bhatt
The presence of an associated coagulopathy and/or the presence of certain anti-phospholipid antibodies have been recently observed in some cases of COVID-19 patients with multiple infarcts [125]. These patients have displayed evidences of ischemia in hands and lower limbs, and bilateral cerebral infarcts in many vascular areas [125]. On hospitalization, laboratory findings of these patients included thrombocytopenia, increased prothrombin time and partial thromboplastin time, leucocytosis, increased level of D-dimer and fibrinogen, and the presence of anti-beta2 glycoprotein IgA and IgG antibodies and anti-cardiolipin IgA antibodies. An important finding was the negative detection of Lupus anticoagulant [125]. These observations point toward a systemic coagulopathy. However, there is a possibility of the lungs being the point of origin of this coagulopathy, which eventually spreads into other vital organs. Hence, it suggests that the etiology of mortality may not be restricted to an uncontrolled inflammatory response but may also include a localized coagulation disorder, which eventually takes systemic effect. Figure 3 highlights the generation and types of coagulation complications, which develop as a result of SARS-CoV-2 mediated cytokine storm.
The effect of oxytocin massage and music on breast milk production and anxiety level of the mothers of premature infants who are in the neonatal intensive care unit: A self-controlled trial
Published in Health Care for Women International, 2022
In our study, listening to music was found to increase the amount of milk more than oxytocin massage (Tables 2 and 3). At the same time, listening to music was the application that increased the breast milk quantity of the mothers more than oxytocin massage and control sessions. The review of the literature has indicated that there are studies addressing the effect of music and oxytocin massage on the release of breast milk separately, but that there is no study in which both of them are examined and compared together. By reducing the occupation of the brain, music allows the mind to relax, brain waves to reduce, more blood to go to the brain. The relaxed mind reduces unnecessary physical stimuli and is effective in the better functioning of the organism (Boşnak et al., 2017). Music is not just about senses. Therefore, it has a positive and systemic effect on human organism (Torun, 2016). Due to this effect, music may have increased the release of milk by relaxing the mothers’ bodies and enhancing the release of oxytocin. Oxytocin massage is thought to have affected oxytocin release, but as it was applied locally, it may have stimulated oxytocin release less than the music intervention. This is the first study in which oxytocin massage and music interventions are compared.
Developing an instrument to assess patient preferences for benefits and risks of treating acute myeloid leukemia to promote patient-focused drug development
Published in Current Medical Research and Opinion, 2018
Jaein Seo, B. Douglas Smith, Elihu Estey, Ernest Voyard, Bernadette O’ Donoghue, John F. P. Bridges
The remaining eight attributes describe possible harms of chemotherapy treatments. Time in hospital for inpatient treatment was selected because over 60% of patients with AML spent time in hospital as inpatients, receiving either potentially curative or supportive treatment38. The need for blood transfusion was selected because essentially all patients with AML receive blood transfusions as a supportive therapy39–43. Fever, infection, nausea, vomiting, decreased appetite, and fatigue were identified as common adverse drug reactions with AML treatments44–51, and organ toxicity was included as a severe adverse drug reaction44,48,52,53. Mental health and chemobrain were included to capture overall patient well-being53–55.
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