Orexin A decreases lipid peroxidation and apoptosis in a novel hypothalamic cell model

Current data support the idea that hypothalamic neuropeptide orexin A (OxA; hypocretin 1) mediates resistance to high fat diet-induced obesity. We previously demonstrated that OxA elevates spontaneous physical activity (SPA), that rodents with high SPA have higher endogenous orexin sensitivity, and that OxA-induced SPA contributes to obesity resistance in rodents. Recent reports show that OxA can confer neuroprotection against ischemic damage, and may decrease lipid peroxidation. This is noteworthy as independent lines of evidence indicate that diets high in saturated fats can decrease SPA, increase hypothalamic apoptosis, and lead to obesity. Together data suggest OxA may protect against obesity both by inducing SPA and by modulation of anti-apoptotic mechanisms. While OxA effects on SPA are well characterized, little is known about the short- and long-term effects of hypothalamic OxA signaling on intracellular neuronal metabolic status, or the physiological relevance of such signaling to SPA. To address this issue, we evaluated the neuroprotective effects of OxA in a novel immortalized primary embryonic rat hypothalamic cell line. We demonstrate for the first time that OxA increases cell viability during hydrogen peroxide challenge, decreases hydrogen peroxide-induced lipid peroxidative stress, and decreases caspase 3/7 induced apoptosis in an in vitro hypothalamic model. Our data support the hypothesis that OxA may promote obesity resistance both by increasing SPA, and by influencing survival of OxA-responsive hypothalamic neurons. Further identification of the individual mediators of the anti-apoptotic and peroxidative effects of OxA on target neurons could lead to therapies designed to maintain elevated SPA and increase obesity resistance.     

Who drops out of treatment for post-traumatic stress disorder?

Significant proportions of participants drop out of cognitive behaviour therapy for post-traumatic stress disorder (PTSD). This study indexed the pretreatment characteristics of civilian trauma survivors who remained in (n = 95) and dropped out (n = 33) of therapy for chronic PTSD. Therapy involved either cognitive behaviour therapy or supportive counselling. Participants who dropped out of therapy had higher scores on the Impact of Event Scale – Avoidance and the Catastrophic Cognitions Questionnaire, controlling for the influence of pretreatment PTSD severity. These finding suggest that retaining participants in therapy for PTSD may be enhanced by focusing initial therapy attention on modification of catastrophic cognitive styles and avoidance tendencies.     

Linking Gambling and Trauma: A Phenomenological Hermeneutic Case Study Using Almaas’ Transformation of Narcissism Approach

The purpose of this article is to examine the phenomenon of pathological gambling and addiction from the perspective of writer and teacher A.H Almaas. By drawing on his Diamond Mind approach we trace the origin of addictive behaviors and pathological gambling to narcissistic wounding, which constitutes the loss of connection with the Essential Identity. A phenomenological hermeneutic methodology was applied in the research process in which Penny, the subject of this case study, willingly shared her life journey through addiction. A thematic analysis clustered into 5 themes revealed a link between her experiences of childhood trauma, addiction, pathological gambling, and the manifestation of fundamental narcissism.     

Are sperm capacitation and apoptosis the opposite ends of a continuum driven by oxidative stress?

This chapter explores the possibility that capacitation and apoptosis are linked processes joined by their common dependence on the continued generation of reactive oxygen species (ROS). According to this model capacitation is initiated in spematozoa following their release into the female reproductive tract as a consequence of intracellular ROS generation, which stimulates intracellular cAMP generation, inhibits tyrosine phosphatase activity and enhances the formation of oxysterols prior to their removal from the sperm surface by albumin. The continued generation of ROS by capacitating populations of spermatozoa eventually overwhelms the limited capacity of these cells to protect themselves from oxidative stress. As a result the over-capacitation of spermatozoa leads to a state of senescence and the activation of a truncated intrinsic apoptotic cascade characterized by enhanced mitochondrial ROS generation, lipid peroxidation, motility loss, caspase activation and phosphatidylserine externalization. The latter may be particularly important in instructing phagocytic leukocytes that the removal of senescent, moribund spermatozoa should be a silent process unaccompanied by the generation of proinflammatory cytokines. These observations reveal the central role played by redox chemistry in defining the life and death of spermatozoa. A knowledge of these mechanisms may help us to engineer novel solutions to both support and preserve the functionality of these highly specialized cells.     

Outcome of Laparoscopic Cholecystectomy in Patients 80 Years and Older

Advanced age is associated with an increase in postoperative complications. This study assesses the indications and outcome for laparoscopic cholecystectomy (LC) in patients aged 80 years or older. Consecutive, unselected patients aged 80 years or over undergoing LC between 1991 and 2000 were included. A retrospective case review enabled analysis of clinical and operative factors together with in-hospital morbidity, 30-day mortality, and duration of hospital stay. A series of 117 patients, 79 women and 38 men with a median age of 83 years (range 80–93 years), underwent LC. Indications for LC were chronic cholecystitis in 62 (53%) patients, acute cholecystitis in 28 (24%), gallstone pancreatitis in 12 (10%), and other conditions in 15 (13%). Six (5%) patients required conversion to an open procedure. Overall, 26 (22%) patients developed a postoperative complication. There were no bile leaks or bile duct injuries. One patient, with gangrenous cholecystitis, died after LC. The median postoperative hospital stay was 3 days (range 1–31 days). LC can be performed safely with low morbidity in patients over age 80 years.This study was presented to the Association of Surgeons of Great Britain and Ireland Annual Meeting, Dublin, Ireland, 2002. It was published in abstract form in the British Journal of Surgery 2002;89(S1):3.     

Components of the Gut Microbiome That Influence Bone Tissue-Level Strength

Modifications to the constituents of the gut microbiome influence bone density and tissue-level strength, but the specific microbial components that influence tissue-level strength in bone are not known. Here, we selectively modify constituents of the gut microbiota using narrow-spectrum antibiotics to identify components of the microbiome associated with changes in bone mechanical and material properties. Male C57BL/6J mice (4 weeks) were divided into seven groups (n = 7–10/group) and had taxa within the gut microbiome removed through dosing with: (i) ampicillin; (ii) neomycin; (iii) vancomycin; (iv) metronidazole; (v) a cocktail of all four antibiotics together (with zero-calorie sweetener to ensure intake); (vi) zero-calorie sweetener only; or (vii) no additive (untreated) for 12 weeks. Individual antibiotics remove only some taxa from the gut, while the cocktail of all four removes almost all microbes. After accounting for differences in geometry, whole bone strength was reduced in animals with gut microbiome modified by neomycin (−28%, p = 0.002) and was increased in the group in which the gut microbiome was altered by sweetener alone (+39%, p < 0.001). Analysis of the fecal microbiota detected seven lower-ranked taxa differentially abundant in animals with impaired tissue-level strength and 14 differentially abundant taxa associated with increased tissue-level strength. Histological and serum markers of bone turnover and trabecular bone volume per tissue volume (BV/TV) did not differ among groups. These findings demonstrate that modifications to the taxonomic components of the gut microbiome have the potential to decrease or increase tissue-level strength of bone independent of bone quantity and without noticeable changes in bone turnover. © 2021 American Society for Bone and Mineral Research (ASBMR).