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Adipocyte Dec 2022Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that interacts via 5 G-protein coupled receptors, S1PR1-5, to regulate signalling pathways critical to...
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that interacts via 5 G-protein coupled receptors, S1PR1-5, to regulate signalling pathways critical to biological processes including cell growth, immune cell trafficking, and inflammation.We demonstrate that in Type 2 diabetic (T2D) subjects, plasma S1P levels significantly increased in response to the anti-diabetic drug, rosiglitazone, and, S1P levels correlated positively with measures of improved glucose homeostasis. In HFD-induced obese C57BL/6 J mice S1PR3 gene expression was increased in adipose tissues (AT) and liver compared with low fat diet (LFD)-fed counterparts. On a HFD, weight gain was similar in both S1PR3-/- mice and WT littermates; however, HFD-fed S1PR3-/- mice exhibited a phenotype of partial lipodystrophy, exacerbated insulin resistance and glucose intolerance. This worsened metabolic phenotype of HFD-fed S1PR3-/- mice was mechanistically linked with increased adipose inflammation, adipose macrophage and T-cell accumulation, hepatic inflammation and hepatic steatosis. In 3T3-L1 preadipocytes S1P increased adipogenesis and S1P-S1PR3 signalling regulated the expression of PPARγ, suggesting a novel role for this signalling pathway in the adipogenic program. These results reveal an anti-diabetic role for S1P, and, that S1P-S1PR3 signalling in the adipose and liver defends against excessive inflammation and steatosis to maintain metabolic homeostasis at key regulatory pathways.
Topics: Animals; Biological Phenomena; Diet, High-Fat; Fatty Liver; Humans; Inflammation; Lysophospholipids; Mice; Mice, Inbred C57BL; Obesity; Sphingosine; Sphingosine-1-Phosphate Receptors
PubMed: 35094654
DOI: 10.1080/21623945.2021.2021700 -
Journal of Diabetes Investigation May 2021A low insulin secretion capacity has been implicated in the high prevalence of non-obese diabetes in East Asians. As alcohol consumption alters insulin and glucose...
AIMS/INTRODUCTION
A low insulin secretion capacity has been implicated in the high prevalence of non-obese diabetes in East Asians. As alcohol consumption alters insulin and glucose metabolism, we tested the hypothesis that alcohol consumption contributes to impaired insulin secretion and glucose intolerance in lean/normal-weight non-diabetic Japanese men.
MATERIALS AND METHODS
This cross-sectional study was undertaken among the residents of Shika town, Japan, between 2011 and 2017. A total of 402 non-diabetic men, including participants with normal fasting plasma glucose (FPG) and impaired FPG (FPG 5.6-6.9 mmol/L), and aged ≥40 years, were examined. FPG, the homeostasis model assessment of insulin secretion capacity (HOMA-B) and alcohol consumption were evaluated and compared between the body mass index (BMI) <25 and BMI ≥25 groups.
RESULTS
HOMA-B levels were lower in the BMI <25 group than in the BMI ≥25 group. Alcohol consumption correlated with a low HOMA-B level regardless of BMI, and, thus, the HOMA-B levels of alcohol drinkers were significantly lower in the BMI <25 group. A multivariable logistic regression analysis showed that alcohol consumption, even light-to-moderate consumption (1-25 g/day), was associated with significantly low levels of HOMA-B and impaired FPG in the BMI <25 group. Among participants with impaired FPG, a low level of HOMA-B was observed in alcohol drinkers, but not in non-drinkers. In contrast, light-to-moderate alcohol consumption was not related to HOMA-B or FPG in the BMI ≥25-group.
CONCLUSION
Alcohol consumption, even a small amount, might contribute to reductions in HOMA-B levels and impaired FPG in lean/normal-weight Japanese men.
Topics: Aged; Alcohol Drinking; Alcohol-Related Disorders; Asian People; Blood Glucose; Body Mass Index; Cross-Sectional Studies; Fasting; Glucose Intolerance; Glycated Hemoglobin; Humans; Ideal Body Weight; Insulin Resistance; Insulin Secretion; Japan; Male; Middle Aged; Prediabetic State
PubMed: 32910554
DOI: 10.1111/jdi.13402 -
International Journal of Mental Health... 2022The COVID-19 pandemic has led to governments taking a number of restrictive measures. Confinement at home during the COVID-19 crisis could have major implications on...
The COVID-19 pandemic has led to governments taking a number of restrictive measures. Confinement at home during the COVID-19 crisis could have major implications on mental health and alcohol use behaviors among the whole population. The present study focuses on the role of individual characteristics, contextual factors, and mental health variables on alcohol consumption. A sample of 2871 adults (79% women) were recruited from the general population through an online self-report questionnaire. Sociodemographic data, lockdown conditions, occupational/physical activity, proximity of contamination, mental health (anxiety, depression, and intolerance of uncertainty), and alcohol consumption (frequency, quantity, and changes) have been assessed. Among participants, 49.1% of the population reported stable alcohol consumption, 24.5% reported a decreased in alcohol consumption since the beginning of the lockdown and 26.4% reported an increase in consumption. Our findings indicate that those individuals who increased their alcohol consumption during the lockdown are often older, working from home, more likely to have children, higher educated, and consume alcohol more frequently and in higher quantities. They also have a greater proximity to contamination and higher levels of anxiety and depression. Our results are discussed in terms of preventive implications.
PubMed: 33424513
DOI: 10.1007/s11469-020-00432-8 -
Respiratory Medicine Apr 2009Patients with COPD usually experience mucus hypersecretion as a result of airway inflammation and response to noxious stimuli. These in turn lead to worsening airway... (Review)
Review
Patients with COPD usually experience mucus hypersecretion as a result of airway inflammation and response to noxious stimuli. These in turn lead to worsening airway resistance, impaired airflow, increased work of breathing, dyspnoea and exercise intolerance. Mucus hypersecretion may also lead to increased exacerbations and poor health related quality of life (HRQL). Institution based pulmonary rehabilitation programs incorporating airway clearance techniques have been shown to improve HRQL, reduce dyspnoea and improve exercise tolerance but are often difficult to provide due to restricted accessibility and resource implications. This review examines the current evidence base and best clinical practice in the area of airway clearance. Mechanical devices such as the flutter valves, positive end expiratory pressure and high frequency chest wall oscillation (HFCWO) may be able to provide the benefits of improved airway clearance in the patient's home potentially with reduced demands on healthcare resources.
Topics: Diuretics, Osmotic; Exercise Therapy; Expectorants; High-Frequency Ventilation; Humans; Mannitol; Mucociliary Clearance; Physical Therapy Modalities; Positive-Pressure Respiration; Pulmonary Disease, Chronic Obstructive; Saline Solution, Hypertonic
PubMed: 19091536
DOI: 10.1016/j.rmed.2008.10.014 -
Journal of Clinical Medicine Oct 2021Auto-brewery syndrome (ABS) is a rare, unstudied, unknown, and underreported phenomenon in modern medicine. Patients with this syndrome become inebriated and may suffer... (Review)
Review
Auto-brewery syndrome (ABS) is a rare, unstudied, unknown, and underreported phenomenon in modern medicine. Patients with this syndrome become inebriated and may suffer the medical and social implications of alcoholism, including arrest for inebriated driving. The pathophysiology of ABS is reportedly due to a fungal type dysbiosis of the gut that ferments some carbohydrates into ethanol and may mimic a food allergy or intolerance. This syndrome should be considered in patients with chronic obstruction or hypomotility presenting with elevated breath and blood alcohol concentrations, especially after a high carbohydrate intake. A glucose challenge test should be performed as the confirmatory test. Treatment typically includes antifungal drugs combined with changes in lifestyle and nutrition. Additional studies are particularly needed on the human microbiome to shed light on how imbalances of commensal bacteria in the gut allow yeast to colonize on a pathological level.
PubMed: 34682761
DOI: 10.3390/jcm10204637 -
Revista Brasileira de Enfermagem 2018to analyze the discourse of women on the interface between marital violence and alcohol use by the partner.
OBJECTIVE
to analyze the discourse of women on the interface between marital violence and alcohol use by the partner.
METHOD
qualitative exploratory research, based on the methodological reference of oral history. We interviewed 19 women with a history of marital violence and involvement with drugs. The data were analyzed through discourse of the collective subject.
RESULTS
the participants' discourse points to consumption of alcohol by partners as a potentiating element of violent episodes, also experienced by their parents, signaling to its transgenerational character; it also calls attention to the danger of marital violence resulting from men's reactions to having their alcohol consumption questioned by their partners.
FINAL CONSIDERATIONS
the study identifies alcohol as a precipitating and/or potentiating factor of conjugal violence, as well as the intergenerational character of violence based on male domination and intolerance.
Topics: Adult; Aged; Alcohol Drinking; Female; Humans; Intimate Partner Violence; Male; Middle Aged; Qualitative Research
PubMed: 30365772
DOI: 10.1590/0034-7167-2017-0540 -
Cardiovascular Diagnosis and Therapy Feb 2020Hypertrophic cardiomyopathy is a genetically determined disorder resulting in left ventricular hypertrophy. In a majority of the estimated 20 million people affected... (Review)
Review
Hypertrophic cardiomyopathy is a genetically determined disorder resulting in left ventricular hypertrophy. In a majority of the estimated 20 million people affected worldwide, left ventricular outflow obstruction is present at rest or with provocation. The presence and degree of obstruction influence the symptomatic presentation, treatment strategies and prognosis of affected individuals. Pharmacologic therapy with beta-adrenergic blocking drugs and calcium channel blockers is the principal treatment strategy in symptomatic patients with left ventricular outflow obstruction but is ineffective in many patients. When symptoms of exertional shortness of breath, chest pain and/or syncope prove refractory to medical therapy and there is persisting left ventricular outflow obstruction, or when there is drug intolerance, septal reduction strategies (surgical myectomy and alcohol septal ablation) are quite effective. Selection of the optimal septal reduction strategy for a given patient has become controversial and is determined largely by the medical system providing treatment strategies for the patient. Regretably, there are no randomized trials comparing myectomy and ablation and none are anticipated. The comprehensive Hypertrophic Cardiomyopathy Guideline Statements published in 2011 and 2014 differ significantly with the earlier statement favoring surgical myectomy and the more recent statement giving equal class I status to the two septal reduction strategies in adult patients with drug-refractory symptoms. Recently published studies of long-term follow-up of patients after alcohol septal ablation in Europe, where surgical myectomy is rarely performed, confirm long-term safety and effectiveness with survival free of cardiac events exceeding 96% at 15 years. The lesser degree of discomfort and more rapid recovery associated with the minimally invasive catheter-based alcohol ablation procedure coupled with the recently published long-term safety data favor an increased use of this strategy in symptomatic adult patients with hypertrophic obstructive cardiomyopathy (HOCM).
PubMed: 32175226
DOI: 10.21037/cdt.2019.07.02 -
The Oncologist Apr 2016The goals of therapy in patients with polycythemia vera (PV) are to improve disease-related symptoms, prevent the incidence or recurrence of thrombosis, and possibly... (Review)
Review
UNLABELLED
The goals of therapy in patients with polycythemia vera (PV) are to improve disease-related symptoms, prevent the incidence or recurrence of thrombosis, and possibly delay or prevent the transformation into myelofibrosis or acute myeloid leukemia (AML). Cytoreductive therapies have been used in older patients and those with a history of thrombosis to achieve these goals. Hydroxyurea (HU) remains the first-line cytoreductive choice; however, up to one in four patients treated with HU over time will develop resistance or intolerance to HU. More importantly, patients who fail HU have a 5.6-fold increase in mortality and a 6.8-fold increase risk of transformation to myelofibrosis or AML; therefore, alternative therapies are needed for these patients. Interferon-α has been used in PV and has shown significant activity in achieving hematologic responses and decreasing JAK2 V617F mutation allele burden. JAK inhibition has also been investigated and recently garnered regulatory approval for this indication. In this review, we will discuss the current treatment options that are available for patients after HU and the novel therapies that are currently under investigation.
IMPLICATIONS FOR PRACTICE
The outcomes of PV patients who fail or who are intolerant of hydroxyurea are poor. Although pegylated interferon can be considered in younger patients, currently, ruxolitinib is the only U.S. Food and Drug Administration-approved agent in this setting, representing a viable option, leading to hematocrit control and a reduction in spleen size and constitutional symptoms. Although a small number of patients will achieve a molecular response with continuous treatment, the implications of such response on the clinical outcomes are still unknown. Patients whose disease is not adequately controlled with ruxolitinib, or who lose their response, can be treated with low-dose busulfan or pipobroman; however, they should be encouraged to participate in trials with novel therapies.
Topics: Busulfan; Cell Proliferation; Humans; Hydroxyurea; Janus Kinase 2; Leukemia, Myeloid, Acute; Nitriles; Polycythemia Vera; Primary Myelofibrosis; Pyrazoles; Pyrimidines; Thrombosis
PubMed: 26975864
DOI: 10.1634/theoncologist.2015-0380 -
The Journal of Pain Jul 2016The risk for misuse of opioid medications is a significant challenge in the management of chronic pain. The identification of those who may be at greater risk for...
UNLABELLED
The risk for misuse of opioid medications is a significant challenge in the management of chronic pain. The identification of those who may be at greater risk for misusing opioids is needed to facilitate closer monitoring of high-risk subgroups, and may help to identify therapeutic targets for mitigating this risk. The aim of this study was to examine whether distress intolerance-the perceived or actual inability to manage negative emotional and somatic states-was associated with opioid misuse in those with chronic pain. A sample of 51 participants prescribed opioid analgesics for chronic back or neck pain were recruited for a 1-time laboratory study. Participants completed measures of distress intolerance and opioid misuse, and a quantitative sensory testing battery. Results suggested that distress intolerance was associated with opioid misuse, even controlling for pain severity and negative affect. Distress intolerance was not associated with pain severity, threshold, or tolerance, but was associated with self-reported anxiety and stress after noxious stimuli. This study found robust differences in distress intolerance between adults with chronic pain with and without opioid medication misuse. Distress intolerance may be a relevant marker of risk for opioid misuse among those with chronic pain.
PERSPECTIVE
This study demonstrated that distress intolerance was associated with opioid misuse in adults with chronic pain who were prescribed opioids. Distress intolerance can be modified with treatment, and thus may be relevant not only for identification of risk for opioid misuse, but also for mitigation of this risk.
Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Catastrophization; Chronic Pain; Female; Humans; Hyperalgesia; Male; Middle Aged; Opioid-Related Disorders; Pain Measurement; Pain Perception; Pain Threshold; Prescription Drug Misuse; Psychiatric Status Rating Scales; Psychophysics; Self Report; Young Adult
PubMed: 27058161
DOI: 10.1016/j.jpain.2016.03.004 -
Emotion (Washington, D.C.) Jun 2023Overreliance on disengagement emotion regulation strategies (e.g., emotion avoidance, emotion suppression) has been shown to relate to poor clinical outcomes. Two traits...
Overreliance on disengagement emotion regulation strategies (e.g., emotion avoidance, emotion suppression) has been shown to relate to poor clinical outcomes. Two traits characterized by difficulties in goal-directed responses to emotion-urgency and distress intolerance-may help explain who is likely to disengage from emotion and when. These traits are associated with diverse forms of psychopathology and greater reliance on disengagement strategies. Gaps remain about how these traits relate to emotion regulation in daily life. The present study uses ecological momentary assessment (EMA) to determine the associations of urgency and distress intolerance with momentary high arousal negative affect and momentary attempts to regulate negative emotions. Participants ( = 101) were college students who endorsed at least weekly behaviors often characterized by emotion dysregulation (e.g., self-harm, binging/purging, alcohol/drug use). Participants completed trait measures at baseline and EMA surveys of momentary affect and emotion regulation, six times daily for 4 days. Results indicated that at certain levels, urgency and distress intolerance moderated the relationship between high arousal negative affect and disengagement from emotion: low urgency scores related to relatively greater disengagement from emotion following reported high arousal negative affect, whereas high distress intolerance scores related to relatively greater disengagement following high arousal negative affect. Findings support the role of both urgency and distress intolerance in the relationship between high arousal negative affect and disengagement, which implicates the utility of clinical interventions that focus on emotion regulation, especially during high arousal states. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Topics: Humans; Emotional Regulation; Ecological Momentary Assessment; Emotions; Arousal; Students
PubMed: 36048037
DOI: 10.1037/emo0001152