Carfentanil exposure could cause severe ventilatory depression associated with muscle stiffness, hypoxemia/hypercapnia (due to hypoventilation) and hypothermia; however, its effect on inspiratory motor drive alone (without these associated effects) has not been investigated. This, along with the inhibitory impact of opioids on hypoxic and hypercapnic ventilation, allows us to determine the impacts of carfentanil on the phrenic nerve (PN) activities before and during hypoxia and hypercapnia in this study. Two groups of anesthetized and spontaneously breathing rats were initially exposed to aerosolized vehicle (Ctrl) and carfentanil (1.7 mg/m3) for 10 min. After vagotomy, paralysis and artificial ventilation, the peak and frequency of integrative PN activity (∫PN and fR), minute PN (MPN = ∫PN × fR), arterial blood pressure (ABP) and heart rate (HR) were recorded before and during hypoxia (10% O2 for 1 min) and hypercapnia (10% CO2 for 3 min). Our results showed that: 1) carfentanil significantly reduced MPN and ∫PN by ~50% and led to hypertension without change in fR and HR; 2) hypoxia enhanced MPN, ∫PN and fR and decreased ABP and hypercapnia brought about similar PN responses with HR decreased in the Ctrl rats; and 3) carfentanil strikingly attenuated the MPN, fR and ∫PN during both chemical challenges and exacerbated the hypotension during hypoxia and the bradycardia during hypercapnia. Our results suggest that carfentanil greatly suppresses the inspiratory motor drive, at least partially, via attenuating the chemoreflexes to substantially contribute to carfentanil-induced ventilatory depression and failure.
The intersection of epidemiology and medical science forms the basis of a public health approach to challenging health issues. Although initial conceptions of epidemiology predominantly focused on infectious diseases, the epidemiological approach has been applied successfully to non-infectious or non-communicable diseases including those health issues related to substance use. However, unlike an infectious disease or even a chronic condition such as cancer, substance use is more dynamic with changing forms of the external agent—psychoactive substances-- and the variety of sources for these ‘agents’ that may vary geographically (within and across communities), as well as sociologically (involving a variety of social groups across time and space). As such, the dynamic nature of substance use warrants an epidemiologically-informed system for its prevention and treatment, that includes on-going monitoring and dynamic and timely surveillance systems designed to identify emerging patterns of use that have implications for prevention and treatment, such as new ways to administer substances (e.g., injecting crack cocaine), new ‘mixtures’ of substances (e.g., changing the composition of substances such as mixing fentanyl with heroin or Adderall), new types of substances, and new user groups. This paper demonstrates how this type of epidemiologic information can inform the structure and function of a national comprehensive substance use service delivery system to address the issue on a population level.
Human papillomavirus (HPV) is a common sexually transmitted infection that can lead to a range of serious health issues, including cervical cancer
Oxytocin is a neuropeptide that has potential for the development as an anti-alcoholism treatment. Clinical studies have recently found that intranasal oxytocin treatment reduces alcohol withdrawal symptoms or craving in alcohol-dependent patients with high anxiety. In rodents, activation of oxytocin receptor by systemic or central administration of oxytocin decreases alcohol reward, consumption and cue-induced alcohol seeking behaviors. The neurobiological interaction between oxytocin and mu opioid receptors (MOR) has been well established: MOR agonists or endogenous beta-endorphin inhibit oxytocin release and neuronal activity. Here we explored whether oxytocin under MOR antagonism by naltrexone can enhance the reduction of alcohol intake by oxytocin alone after 3-week excessive alcohol drinking in an intermittent access alcohol (IAA) mouse model or after 1-week abstinence in mouse alcohol deprivation effect (ADE) model. For a genetic control for naltrexone effect, neuronal proopiomelanocortin enhancer (nPE) knockout mice with brain-specific beta-endorphin deficiency were further studied with oxytocin. We found that administration of oxytocin at 0.1 mg/kg [but not 0.01 or 0.03 mg/kg] decreased alcohol intake and preference. When oxytocin co- administered with naltrexone, oxytocin at 0.01-0.03 mg/kg with low doses of naltrexone (0.5 or 1 mg/kg) reduced alcohol drinking more profoundly than the sub-effective doses of oxytocin alone. Alcohol “relapse” in the ADE was prevented by either oxytocin alone or co-administration of oxytocin with naltrexone. The oxytocin effect was confirmed in nPE-/- mice, suggesting independent mechanisms by which oxytocin and naltrexone reduced alcohol drinking. Our study suggests that oxytocin in combination with low-dose naltrexone offers a novel strategy in alcoholism treatment.
Background:Depression in the peripartum period is prevalent in low-income-countries. The identification of women needing referral is often lacking and on the other hand, women in need of support and treatment do not make use of existing support.Objectives:To identify risk factors for fetal and postnatal consequences of depression in pregnancy and to investigate further management once women at risk have been identified.Methods:The Safe Passage Study was a large prospective multicenter international study. Extensive information, including the Edinburgh postnatal depression scale (EPDS), was collected during the study. At risk women were referred to the study's social worker (SW). Women were categorized according to risk on their EPDS results. Risk categories were characterized and investigated for infant outcomes.Results:Data from 5,489 women were available for analysis and revealed a 51% prevalence of prenatal depression. Fourteen percent of at-risk women attended SW appointments, while 36% accepted the SW referral but persistently failed to attend. At risk women were significantly younger, had less formal education, had lower monthly income, and lived in more crowded conditions. They used significantly more alcohol and cigarettes. Their infants had shorter gestational ages, lower birth weights and were more growth restricted. Infants of depressed women who missed appointments weighed less and were more growth restricted.Conclusion:Women with high EPDSs had less favorable socioeconomic conditions, used more alcohol or tobacco during pregnancy, and their infants weighed less with more growth restriction. Women who repeatedly missed their appointments came from the poorest socioeconomic conditions and their infants had worse birth outcomes.
