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1.
Geroscience ; 46(1): 517-530, 2024 Feb.
Article En | MEDLINE | ID: mdl-38153668

Treatment of Alzheimer's disease (AD) has been limited to managing of symptoms or anti-amyloid therapy with limited results and uncertainty. Seeking out new therapies that can reverse the effects of this devastating disease is important. Hyperbaric oxygen (HBO) therapy could be such a candidate as it has been shown to improve brain function in certain neurological conditions. Furthermore, the role sex plays in the vulnerability/resilience to AD remains equivocal. An understanding of what makes one sex more vulnerable to AD could unveil new pathways for therapy development. In this study, we investigated the effects of HBO on cognitive, motor, and affective function in a mouse model of AD (5xFAD) and assessed protein oxidation in peripheral tissues as a safety indicator. The motor and cognitive abilities of 5xFAD mice were significantly impaired. HBO therapy improved cognitive flexibility and associative learning of 5xFAD females but not males, but HBO had no effect other aspects of cognition. HBO also reversed AD-related declines in balance but had no impact on gait and anxiety-like behavior. HBO did not affect body weights or oxidative stress in peripheral tissues. Our study provides further support for HBO therapy as a potential treatment for AD and emphasizes the importance of considering sex as a biological variable in therapeutic development. Further investigations into the underlying mechanisms of HBO's sex-specific responses are warranted, as well as optimizing treatment protocols for maximum benefits.


Alzheimer Disease , Hyperbaric Oxygenation , Male , Mice , Animals , Female , Alzheimer Disease/drug therapy , Cognition , Oxygen , Oxidative Stress/physiology
2.
Geroscience ; 45(2): 747-756, 2023 04.
Article En | MEDLINE | ID: mdl-36525211

The World Health Organization estimates that by the year 2040, neurodegenerative diseases will be the second leading cause of death in developed countries, overtaking cancer-related deaths and exceeded only by cardiovascular disease-related death. The search for interventions has therefore become paramount to alleviate some of this burden. Based on pathways affected in neurodegenerative diseases, hyperbaric oxygen treatment (HBOT) could be a good candidate. This therapy has been used for the past 50 years for conditions such as decompression sickness and wound healing and has been shown to have promising effects in conditions associated with neurodegeneration and functional impairments. The goal of this review was to explore the history of hyperbaric oxygen therapy, its uses, and benefits, and to evaluate its effectiveness as an intervention in treating neurodegenerative diseases. Additionally, we examined common mechanisms underlying the effects of HBOT in different neurodegenerative diseases, with a special emphasis on epigenetics.


Hyperbaric Oxygenation , Neurodegenerative Diseases , Humans , Neurodegenerative Diseases/therapy , Wound Healing
3.
Endocrinology ; 162(11)2021 11 01.
Article En | MEDLINE | ID: mdl-34467976

Neurodegenerative diseases cause severe impairments in cognitive and motor function. With an increasing aging population and the onset of these diseases between 50 and 70 years, the consequences are bound to be devastating. While age and longevity are the main risk factors for neurodegenerative diseases, sex is also an important risk factor. The characteristic of sex is multifaceted, encompassing sex chromosome complement, sex hormones (estrogens and androgens), and sex hormone receptors. Sex hormone receptors can induce various signaling cascades, ranging from genomic transcription to intracellular signaling pathways that are dependent on the health of the cell. Oxidative stress, associated with aging, can impact the health of the cell. Sex hormones can be neuroprotective under low oxidative stress conditions but not in high oxidative stress conditions. An understudied sex hormone receptor that can induce activation of oxidative stress signaling is the membrane androgen receptor (mAR). mAR can mediate nicotinamide adenine dinucleotide-phosphate (NADPH) oxidase (NOX)-generated oxidative stress that is associated with several neurodegenerative diseases, such as Alzheimer disease. Further complicating this is that aging can alter sex hormone signaling. Prior to menopause, women experience more estrogens than androgens. During menopause, this sex hormone profile switches in women due to the dramatic ovarian loss of 17ß-estradiol with maintained ovarian androgen (testosterone, androstenedione) production. Indeed, aging men have higher estrogens than aging women due to aromatization of androgens to estrogens. Therefore, higher activation of mAR-NOX signaling could occur in menopausal women compared with aged men, mediating the observed sex differences. Understanding of these signaling cascades could provide therapeutic targets for neurodegenerative diseases.


Gonadal Steroid Hormones/physiology , Neurodegenerative Diseases/etiology , Oxidative Stress/physiology , Sex Characteristics , Aging/physiology , Androgens/metabolism , Androgens/physiology , Animals , Estrogens/metabolism , Estrogens/physiology , Female , Humans , Male , Neurodegenerative Diseases/epidemiology , Neurodegenerative Diseases/therapy
4.
Antibiotics (Basel) ; 10(2)2021 Feb 18.
Article En | MEDLINE | ID: mdl-33670731

A standardised Global Point Prevalence Survey (PPS) tool was used to determine the antimicrobial prescription pattern in the Ho Teaching Hospital on two separate occasions in a total of 14 wards in the hospital, including dedicated wards for paediatrics and neonates. Manually collected and anonymised data were entered, validated, analysed and reported using a web-based global PPS application. With 147 and 153 patients considered in the July 2019 and January 2020 surveys, respectively, 98 patients (66.7%) and 84 patients (54.9%) had received one or more antimicrobials. The prevalence of antimicrobial use in the adult wards was 64.3% (72/112) and 53.4% (63/118) in the first and second surveys, respectively. The prevalence in the paediatric wards was 60.0% (12/20) and 62.5% (10/16), respectively, in the two surveys, while that in the neonatal wards was 93.3% (14/15) and 57.9% (11/19), respectively. ß-lactams were the most used antibiotics in both periods. Malaria was the most common diagnosis requiring the use of antimicrobials in July 2019, accounting for 19.4% of the diagnoses, whereas in January 2020, it was skin and soft-tissue conditions (28.1%). This reflects a seasonal association between malaria and rainfall patterns. Out of the antimicrobials prescribed during each of the survey periods, 95% were used for empirical treatment, and this could be attributed to a number of reasons, including logistical challenges, among others, that require further exploration in the context of local, national and international policy recommendations.

5.
Antibiotics (Basel) ; 11(1)2021 Dec 22.
Article En | MEDLINE | ID: mdl-35052883

Antimicrobial resistance (AMR) is a significant problem in global health today, particularly in low- and middle-income countries (LMICs) where antimicrobial stewardship programmes are yet to be successfully implemented. We established a partnership between AMR pharmacists from a UK NHS hospital and in Ho Teaching Hospital with the aim of enhancing antimicrobial stewardship knowledge and practice among healthcare providers through an educational intervention. We employed a mixed-method approach that included an initial survey on knowledge and awareness before and after training, followed by qualitative interviews with healthcare providers conducted six months after delivery of training. This study was carried out in two phases in Ho Teaching Hospital with healthcare professionals, including pharmacists, medical doctors, nurses and medical laboratory scientists. Ethical approval was obtained prior to data collection. In the first phase, we surveyed 50 healthcare providers, including nurses (33%), pharmacists (29%) and biomedical scientists (23%). Of these, 58% of participants had engaged in continuous professional development on AMR/AMS, and above 95% demonstrated good knowledge on the general use of antibiotics. A total of 18 participants, which included four medical doctors, five pharmacists, four nurses, two midwives and three biomedical scientists, were interviewed in the second phase and demonstrated greater awareness of AMS practices, particularly the role of education for patients, as well as healthcare professionals. We found that knowledge and practice with AMS was markedly improved six months after the training session. There is limited practice of AMS in LMICs; however, through AMR-focused training, we demonstrated improved AMS skills and practice among healthcare providers in Ho Teaching Hospital. There is a need for continuous AMR training sessions for healthcare professionals in resource-limited settings.

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