Browsing by Subject "sex differences"

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    ItemOpen Access
    An In Vivo Definition of Brain Histamine Dynamics Reveals Critical Neuromodulatory Roles for This Elusive Messenger.
    (International journal of molecular sciences, 2022-11) Berger, Shane N; Baumberger, Beatrice; Samaranayake, Srimal; Hersey, Melinda; Mena, Sergio; Bain, Ian; Duncan, William; Reed, Michael C; Nijhout, H Frederik; Best, Janet; Hashemi, Parastoo
    Histamine is well known for mediating peripheral inflammation; however, this amine is also found in high concentrations in the brain where its roles are much less known. In vivo chemical dynamics are difficult to measure, thus fundamental aspects of histamine's neurochemistry remain undefined. In this work, we undertake the first in-depth characterization of real time in vivo histamine dynamics using fast electrochemical tools. We find that histamine release is sensitive to pharmacological manipulation at the level of synthesis, packaging, autoreceptors and metabolism. We find two breakthrough aspects of histamine modulation. First, differences in H3 receptor regulation between sexes show that histamine release in female mice is much more tightly regulated than in male mice under H3 or inflammatory drug challenge. We hypothesize that this finding may contribute to hormone-mediated neuroprotection mechanisms in female mice. Second, a high dose of a commonly available antihistamine, the H1 receptor inverse agonist diphenhydramine, rapidly decreases serotonin levels. This finding highlights the sheer significance of pharmaceuticals on neuromodulation. Our study opens the path to better understanding and treating histamine related disorders of the brain (such as neuroinflammation), emphasizing that sex and modulation (of serotonin) are critical factors to consider when studying/designing new histamine targeting therapeutics.
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    Females have Lower Knee Strength and Vertical Ground Reaction Forces During Landing than Males Following Anterior Cruciate Ligament Reconstruction at the Time of Return to Sport.
    (International journal of sports physical therapy, 2022-01) Sullivan, Zachary B; Sugarman, Barrie S; Faherty, Mallory S; Killelea, Carrie; Taylor, Dean C; Le, Daniel; Toth, Alison P; Riboh, Jonathan C; Diehl, Lee H; Wittstein, Jocelyn R; Amendola, Annunziato; Sell, Timothy C

    Purpose

    There is a high rate of second anterior cruciate ligament (ACL) injury (ipsilateral graft or contralateral ACL) upon return-to-sport (RTS) following ACL reconstruction (ACLR). While a significant amount of epidemiological data exists demonstrating sex differences as risk factors for primary ACL injury, less is known about sex differences as potential risk factors for second ACL injury. The purpose of this study is to determine if there are sex-specific differences in potential risk factors for second ACL injury at the time of clearance for RTS.

    Methods

    Ten male and eight female athletes (age: 20.8 years ±6.3, height: 173.2 cm ±10.1, mass: 76.6 kg ±18.3) participated in the study following ACLR at time of RTS (mean 10.2 months). Performance in lower extremity isokinetic and isometric strength testing, static and dynamic postural stability testing, and a single leg stop-jump task was compared between the sexes.

    Results

    Normalized for body weight, males had significantly greater isokinetic knee flexion (141±14.1 Nm/kg vs. 78±27.4 Nm/kg, p=0.001) and extension strength (216±45.5 Nm/kg vs. 159±53.9 Nm/kg, p=0.013) as well as isometric flexion (21.1±6.87% body weight vs. 12.5±5.57% body weight, p=0.013) and extension (41.1±7.34% body weight vs. 27.3±11.0% body weight, p=0.016) strength compared to females. In the single-leg stop jump task, males had a greater maximum vertical ground reaction force during landing (332±85.5% vs. 259±27.4% body weight, p=0.027) compared to females.

    Conclusions

    Based on these results, there are significant differences between sexes following ACLR at the time of RTS. Lower knee flexion and extension strength may be a potential risk factor for second ACL injury among females. Alternatively, the increased maximum vertical force observed in males may be a potential risk factor of second ACL injury in males. Although these results should be interpreted with some caution, they support that rehabilitation programs in the post-ACLR population should be individualized based on the sex of the individual.

    Level of evidence

    Level 3.
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    ItemOpen Access
    Ketamine Differentially Attenuates Alcohol Intake in Male Versus Female Alcohol Preferring (P) Rats.
    (Journal of drug and alcohol research, 2017-01) Rezvani, Amir H; Levin, Edward D; Cauley, Marty; Getachew, Bruk; Tizabi, Yousef
    Although various pharmacological tools in combating addiction to alcohol are available, their efficacy is limited. Hence, there is a critical need for development of more effective medications. Recent advances in the field have identified the glutamatergic system as a potential novel target for intervention in addictive behaviors. Hence, we evaluated the effects of acute administration of low (subanesthetic) doses of ketamine, an NMDA receptor antagonist, on alcohol intake and alcohol preference in both male and female rats. Adult alcohol preferring (P) rats were exposed to two-bottle choice (ethanol 10% and water) for at least three weeks following a nine-day training period and the effects of various doses of ketamine (5 mg/kg, 7.5 mg/kg, and 10 mg/kg, injected subcutaneously, SC) on consumption of alcohol over various time periods during a 24 h interval were measured. Our results indicate that ketamine treatment significantly reduced both alcohol intake and preference in a time- and dose-dependent manner in both sexes. Moreover, a differential sensitivity between the sexes was observed. Thus, although alcohol intake was higher in males, female rats responded much more strongly to the highest dose of ketamine than males in the initial time periods. It is concluded that glutamatergic receptor manipulations may be of therapeutic potential in addiction to alcohol and that different sexes may respond differentially to such treatments.
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    Optimal Versus Realized Trajectories of Physiological Dysregulation in Aging and Their Relation to Sex-Specific Mortality Risk.
    (Front Public Health, 2016) Arbeev, Konstantin G; Cohen, Alan A; Arbeeva, Liubov S; Milot, Emmanuel; Stallard, Eric; Kulminski, Alexander M; Akushevich, Igor; Ukraintseva, Svetlana V; Christensen, Kaare; Yashin, Anatoliy I
    While longitudinal changes in biomarker levels and their impact on health have been characterized for individual markers, little is known about how overall marker profiles may change during aging and affect mortality risk. We implemented the recently developed measure of physiological dysregulation based on the statistical distance of biomarker profiles in the framework of the stochastic process model of aging, using data on blood pressure, heart rate, cholesterol, glucose, hematocrit, body mass index, and mortality in the Framingham original cohort. This allowed us to evaluate how physiological dysregulation is related to different aging-related characteristics such as decline in stress resistance and adaptive capacity (which typically are not observed in the data and thus can be analyzed only indirectly), and, ultimately, to estimate how such dynamic relationships increase mortality risk with age. We found that physiological dysregulation increases with age; that increased dysregulation is associated with increased mortality, and increasingly so with age; and that, in most but not all cases, there is a decreasing ability to return quickly to baseline physiological state with age. We also revealed substantial sex differences in these processes, with women becoming dysregulated more quickly but with men showing a much greater sensitivity to dysregulation in terms of mortality risk.
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    Sources of Misused Prescription Opioids and Their Association with Prescription Opioid Use Disorder in the United States: Sex and Age Differences.
    (Substance use & misuse, 2020-01-24) Park, Ji-Yeun; Wu, Li-Tzy
    Background: Prescription opioid (PO) misuse and prescription opioid use disorder (POUD) are a national crisis in the USA. To inform strategies for reducing the PO epidemic, research is needed on the sources of misused POs and their association with POUD. Methods: Past-year PO misusers aged ≥12 (N = 6033) from the 2015 to 2016 National Surveys on Drug Use and Health were analyzed. The most recent source of misused POs was assessed. Logistic regression analyses were used to determine the association between the sources of misused POs and past-year POUD. All analyses were stratified by age groups for each sex. Results: Overall, the most common sources of misused POs were obtaining from friends/relatives for free (40.27%) and physicians (36.59%). Males had a higher prevalence of buying POs from friends/relatives or drug dealers/strangers than females. Significant age differences also emerged. Buying POs from drug dealers/strangers (vs. obtaining POs free from friends/relatives) was strong predictor of past-year POUD in both sexes. In the sex- and age-stratified analyses, significant associations of past-year POUD with (1) buying from drug dealers/strangers emerged among males aged 18+ and females aged 26+; (2) buying from friends/relatives emerged among males aged 12+ and females aged 18-25; (3) obtaining from physicians emerged among males aged 18+ and females aged 26+. Conclusions: Our findings indicate different risk profiles for POUD across sex and age groups with different diversion sources. Prevention and treatment programs for POUD should be tailored to consider sex and developmental age differences in sources of opioids.