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Cholecystokinin and Neuroendocrine Secretion
Published in Craig A. Johnston, Charles D. Barnes, Brain-Gut Peptides and Reproductive Function, 2020
Joseph G. Verbalis, Edward M. Stricker
In considering what central pathways might mediate inhibition of food intake following peripheral injections of CCK, two potential candidates stand out. The first of these includes the spectrum of neural pathways activated by stress responses. Observations that peripheral injection of CCK in rats increases secretion of OT, prolactin, and ACTH is consistent with the concept that this represents a neuroendocrine stress response to a viscerally aversive agent. However, this may be too simplistic an explanation to account for the observed OT secretion. Specifically, it is well known that all stressors do not stimulate secretion of OT in rats. For example, hypoglycemia and hypothermia do not stimulate OT secretion (Gibbs, 1986), and it is noteworthy that both of these stressors are known to increase rather than decrease food intake. Thus, central oxytocinergic pathways seem to be activated by stressors that decrease food intake, but not by stressors that do not change or even increase food intake. In this regard, it is interesting to note that intracerebroventricular CRH also has been shown to be a potent inhibitor of food intake (Morley and Levine, 1982), that stress-induced hypothalamic CRH secretion has been shown to mediate the anorexia accompanying various stress states (Lenz et al., 1988), and that intracerebroventricular injection of CRH has been shown to cause an increase in pituitary OT secretion (Bruhn et al., 1986). Thus, these observations may represent another example of activation of the oxytocinergic component of the stress response that may be more specifically associated with inhibition of food intake.
The treatment of hepatocellular carcinoma with SP94 modified asymmetrical bilayer lipid-encapsulated Cu(DDC)2 nanoparticles facilitating Cu accumulation in the tumor
Published in Expert Opinion on Drug Delivery, 2023
Hao Liu, Yihan Kong, Xue Liang, Zixu Liu, Xueting Guo, Bing Yang, Tian Yin, Haibing He, Jingxin Gou, Yu Zhang, Xing Tang
The optimal way to design a novel drug is to start with an old one. Repurposing existing drugs to treat cancer is a shortcut to overcome the expensive and lengthy drug development process [7,8]. Disulfiram (DSF) has been employed as a safe and effective alcohol-aversive agent for treating alcohol dependence since 1948 [9,10]. In recent years, numerous investigations have shown that DSF exerts an excellent copper-dependent anticancer effect [11–15]. Copper ion has been found as vital trace element of life and involves several aspects of cellular metabolism in living organisms (e.g. the energy production of the mitochondria and the promotion of angiogenesis [16]). In serum and tissues of numerous types of human cancers, copper levels were found to be higher than that of the normal tissues. However, the absolute copper level in tumors is till insufficient to increase the chemotherapeutic activity of DSF.
Promising treatment strategies to combat Staphylococcus aureus biofilm infections: an updated review
Published in Biofouling, 2020
P. S. Seethalakshmi, Riya Rajeev, George Seghal Kiran, Joseph Selvin
Disulfiram is an FDA approved medication used as an aversive agent in patients with chronic alcoholism (Ellis and Dronsfield 2013). Recent studies have proven that disulfiram has antimicrobial potential against antibiotic-resistant bacteria such as Mycobacterium tuberculosis and S. aureus (Horita et al. 2012; Long 2017). Disulfiram eradicated S. aureus biofilms much more effectively than the antibiotics levofloxacin, and vancomycin (Thakare et al. 2019). Besides biofilms, intracellular reservoirs of S. aureus can also lead to recurrent infections (Fowler et al. 2005). Disulfiram showed efficient elimination of intracellular S. aureus from infected mouse macrophage cells and a reduced bacterial load in mouse models. The MIC value of disulfiram did not differ with respect to virulence factors and was equally effective against antibiotic-resistant and sensitive strains of S. aureus, suggesting a novel inhibitory mechanism (Thakare et al. 2019). Given below is a summary of drugs that have been repurposed as anti-biofilm agents of S. aureus (Table 2; Figure 3).
Domiciliary alcohol detoxification outcomes: a study from Goa, India
Published in Journal of Addictive Diseases, 2020
Saumitra Nemlekar, Pooja Gaonkar, Anil Rane
The regimen followed in the above sample was fixed dose outpatient detoxification. The key findings of our study were unfavorable outcome in 65% that is nearly 2 out of 3 patients did not complete treatment. Success rates even in highly structured intensive outpatient treatment programs were at 64%.11 Of this 72% had dropped out of treatment at some time of their follow up. At three years the same cohort had abstention rates of only 43%.11 Studies have been unable to find predictors of outcomes or confirm the roles of such determinants.11–13 The reasons for unfavorable outcomes in alcohol include prior detoxification, multiple treatments, higher levels of depression and anxiety and suicidal attempts prior to treatment. Patient factors identified have been socio-economic level, lower education and earlier onset. Most importantly treatment dropout has been found to significantly predict relapse with robust evidence of relapse being highest in nonresidential and outpatient treatment settings.14–16 One study reported use of adjuvant medications (aversive agent (disulfiram)), older age, frequent drinking and severe alcohol dependence to be associated with better outcome at four weeks.17