In recent years, interest in the relationship between gut microbiota and disease states has grown considerably. Indeed, several strategies have been employed to modify the microbiome through the ...administration of different diets, by the administration of antibiotics or probiotics, or even by transplantation of feces. In the present manuscript, we focus specifically on the potential application of probiotics, which seem to be a safe strategy, in the management of digestive, pain, and emotional disorders. We present evidence from animal models and human studies, notwithstanding that translation to clinic still deserves further investigation. The microbiome influences gut functions as well as neurological activity by a variety of mechanisms, which are also discussed. The design and performance of larger trials is urgently needed to verify whether these new strategies might be useful not only for the treatment of disorders affecting the gastrointestinal tract but also in the management of emotional and pain disorders not directly related to the gut.
Public concern on mental health has noticeably increased given the high prevalence of neuropsychiatric disorders. Cognition and emotionality are the most affected functions in neuropsychiatric ...disorders, i.e., anxiety disorders, depression, and schizophrenia. In this review, most relevant literature on the role of the endocannabinoid (eCB) system in neuropsychiatric disorders will be presented. Evidence from clinical and animal studies is provided for the participation of CB1 and CB2 receptors (CB1R and CB2R) in the above mentioned neuropsychiatric disorders. CBRs are crucial in some of the emotional and cognitive impairments reported, although more research is required to understand the specific role of the eCB system in neuropsychiatric disorders. Cannabidiol (CBD), the main non-psychotropic component of the Cannabis sativa plant, has shown therapeutic potential in several neuropsychiatric disorders. Although further studies are needed, recent studies indicate that CBD therapeutic effects may partially depend on facilitation of eCB-mediated neurotransmission. Last but not least, this review includes recent findings on the role of the eCB system in eating disorders. A deregulation of the eCB system has been proposed to be in the bases of several neuropsychiatric disorders, including eating disorders. Cannabis consumption has been related to the appearance of psychotic symptoms and schizophrenia. In contrast, the pharmacological manipulation of this eCB system has been proposed as a potential strategy for the treatment of anxiety disorders, depression, and anorexia nervosa. In conclusion, the eCB system plays a critical role in psychiatry; however, detrimental consequences of manipulating this endogenous system cannot be underestimated over the potential and promising perspectives of its therapeutic manipulation.
Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis. In the present study we have investigated the long-term effects of ...administering increasing doses of delta-9-tetrahydrocannabinol THC; 2.5, 5, 10 mg/kg; i.p. from postnatal day (pnd) 28 to 45, alone and/or in conjunction with 3,4-methylenedioxymethamphetamine MDMA; two daily doses of 10 mg/kg every 5 days; s.c. from pnd 30 to 45, in both male and female Wistar rats. When tested one day after the end of the pharmacological treatment (pnd 46), MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze. In the long-term, cognitive functions in the novel object test were seen to be disrupted by THC administration to female but not male rats. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied (80 dB), whereas in combination with THC it induced a similar decrease at 75 dB. THC decreased hippocampal Arc expression in both sexes, while in the frontal cortex this reduction was only evident in females. MDMA induced a reduction in ERK1/2 immunoreactivity in the frontal cortex of male but not female animals, and THC decreased prepro-orexin mRNA levels in the hypothalamus of males, although this effect was prevented when the animals also received MDMA. The results presented indicate that adolescent exposure to THC and/or MDMA induces long-term, sex-dependent psychophysiological alterations and they reveal functional interactions between the two drugs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cannabinoid agonists induce complex and often contradictory effects on anxiety in humans and experimental animals. The data from animal tests provide evidence of dose-dependent bidirectional ...modulation of anxiety by the cannabinoid system and the importance of environmental context. The mechanisms mediating the effects of cannabinoids on anxiety-related responses appear to involve CB
1 and non-CB
1 cannabinoid receptors. In addition, the CRH, GABA
A, cholecystokinin, opioid and serotonergic systems have also been implicated. Brain regions such as the amygdala, hippocampus and cortex, directly involved in the regulation of emotional behavior, contain high densities of CB
1 receptors. Mutant mice lacking CB
1 receptors show anxiogenic-like and depressive-like phenotypes in several tests, as well as profound alterations in their adrenocortical activity. Pharmacological blockade of CB
1 receptors induces anxiety in rats, and inhibition of anandamide metabolism produces anxiolytic-like effects. Thus, the endocannabinoid system appears to play a pivotal role in the regulation of emotional states and may constitute a novel pharmacological target for anti-anxiety therapy.
The endocannabinoid system is involved in several physiological and pathological states including anxiety, depression, addiction and other neuropsychiatric disorders. Evidence from human and rodent ...studies suggests that exposure to early life stress may increase the risk of psychopathology later in life. Indeed, maternal deprivation (MD) (24 h at postnatal day 9) in rats induces behavioural alterations associated with depressive-like and psychotic-like symptoms, as well as important changes in the endocannabinoid system. As most neuropsychiatric disorders first appear at adolescence, and show remarkable sexual dimorphisms in their prevalence and severity, in the present study, we analysed the gene expression of the main components of the brain cannabinoid system in adolescent (postnatal day 46) Wistar male and female rats reared under standard conditions or exposed to MD. For this, we analysed, by real-time quantitative PCR, the expression of genes encoding for CB1 and CB2 receptors, TRPV1 and GPR55 (Cnr1, Cnr2a, Cnr2b, Trpv1, and Gpr55), for the major enzymes of synthesis, N-acyl phosphatidyl-ethanolamine phospholipase D (NAPE-PLD) and diacylglycerol lipase (DAGL) (Nape-pld, Dagla and Daglb), and degradation, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) (Faah, Magl and Cox-2), in specific brain regions, that is, the frontal cortex, ventral and dorsal striatum, dorsal hippocampus and amygdala. In males, MD increased the genetic expression of all the genes studied within the frontal cortex, whereas in females such an increase was observed only in the hippocampus. In conclusion, the endocannabinoid system is sensitive to early life stress at the gene expression level in a sex-dependent and region-dependent manner, and these changes are already evident in the adolescent brain.
Sensory processing dysfunction (SPD) is characterized by a behaviorally observed difference in the response to sensory information from the environment. While the cerebellum is involved in normal ...sensory processing, it has not yet been examined in SPD. Diffusion tensor imaging scans of children with SPD (
= 42) and typically developing controls (TDC;
= 39) were compared for fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) across the following cerebellar tracts: the middle cerebellar peduncles (MCP), superior cerebellar peduncles (SCP), and cerebral peduncles (CP). Compared to TDC, children with SPD show reduced microstructural integrity of the SCP and MCP, characterized by reduced FA and increased MD and RD, which correlates with abnormal auditory behavior, multisensory integration, and attention, but not tactile behavior or direct measures of auditory discrimination. In contradistinction, decreased CP microstructural integrity in SPD correlates with abnormal tactile and auditory behavior and direct measures of auditory discrimination, but not multisensory integration or attention. Hence, altered cerebellar white matter organization is associated with complex sensory behavior and attention in SPD, which prompts further consideration of diagnostic measures and treatments to better serve affected individuals.
An estimated 20% to 30% of the global population has suffered a vertiginous episode. Among them, 20% do not receive a clear diagnosis. Improved methods, indicators and metrics are necessary to assess ...the sensory systems related to balance, especially when patients are undergoing treatment for vertiginous episodes. Patients with balance disorders should be monitored for changes at the individual level to gather objective information. In this study, we evaluate the use of the MCQ-Balance (Measure, Classify and Qualify) assessment for examining a patient's balance progression using tests to measure static balance control and dynamic postural balance with a stabilometric platform.
The MCQ-Balance assessment comprises three stages: (i) measuring the progression of each variable between two separate and consecutive days (called sessions) using the Magnitude-Based Decision analysis; (ii) classifying the progression of the patient's balance with a score; and (iii) qualifying the progression of the patient's balance from the resulting scores using a set of rules. This method was applied to 42 patients with balance disorders of peripheral or central origin characterised by vertigo as the cardinal symptom. Balance progression was measured using the MCQ-Balance assessment over the course of three months, and these results were compared with the assessment of a clinical expert.
The MCQ-Balance assessment showed an accuracy of 83.4% and a Cohen's Kappa coefficient of 0.752 compared to the assessment of a clinical expert.
The MCQ-Balance assessment facilitates the monitoring of patient balance and provides objective information that has the potential to improve medical decision making and the adjustment of individual treatment.
Wernicke’s encephalopathy (WE) is a neurologic disease caused by vitamin B1 or thiamine deficiency (TD), being the alcohol use disorder its main risk factor. WE patients present limiting motor, ...cognitive, and emotional alterations related to a selective cerebral vulnerability. Neuroinflammation has been proposed to be one of the phenomena that contribute to brain damage. Our previous studies provide evidence for the involvement of the innate immune receptor Toll-like (TLR)4 in the inflammatory response induced in the frontal cortex and cerebellum in TD animal models (animals fed with TD diet TDD and receiving pyrithiamine). Nevertheless, the effects of the combination of chronic alcohol consumption and TD on TLR4 and their specific contribution to the pathogenesis of WE are currently unknown. In addition, no studies on TLR4 have been conducted on WE patients since brains from these patients are difficult to achieve. Here, we used rat models of chronic alcohol (CA; 9 months of forced consumption of 20% (w/v) alcohol), TD hit (TDD + daily 0.25 mg/kg i.p. pyrithiamine during 12 days), or combined treatment (CA + TDD) to check the activation of the proinflammatory TLR4/MyD88 pathway and related markers in the frontal cortex and the cerebellum. In addition, we characterized for the first time the TLR4 and its coreceptor MyD88 signature, along with other markers of this proinflammatory signaling such as phospo-NFκB p65 and IκBα, in the postmortem human frontal cortex and cerebellum (gray and white matter) of an alcohol-induced WE patient, comparing it with negative (no disease) and positive (aged brain with Alzheimer’s disease) control subjects for neuroinflammation. We found an increase in the cortical TLR4 and its adaptor molecule MyD88, together with an upregulation of the proinflammatory signaling molecules p-NF-ĸB and IĸBα in the CA + TDD animal model. In the patient diagnosed with alcohol-induced WE, we observed cortical and cerebellar upregulation of the TLR4/MyD88 pathway. Hence, our findings provide evidence, both in the animal model and the human postmortem brain, of the upregulation of the TLR4/MyD88 proinflammatory pathway in alcohol consumption–related WE.
Albuminuria is common in patients with heart failure and associated with worse outcomes. The underlying pathophysiological mechanism of albuminuria in heart failure is still incompletely understood. ...The association of clinical characteristics and biomarker profile with albuminuria in patients with heart failure with both reduced and preserved ejection fractions were evaluated.
Two thousand three hundred and fifteen patients included in the index cohort of BIOSTAT-CHF were evaluated and findings were validated in the independent BIOSTAT-CHF validation cohort (1431 patients). Micro-albuminuria and macro-albuminuria were defined as urinary albumincreatinine ratio (UACR) 30 mg/gCr and 300 mg/gCr in spot urines, respectively. The prevalence of micro- and macro-albuminuria was 35.4 and 10.0, respectively. Patients with albuminuria had more severe heart failure, as indicated by inclusion during admission, higher New York Heart Association functional class, more clinical signs and symptoms of congestion, and higher concentrations of biomarkers related to congestion, such as biologically active adrenomedullin, cancer antigen 125, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (all P 0.001). The presence of albuminuria was associated with increased risk of mortality and heart failure (re)hospitalization in both cohorts. The strongest independent association with log UACR was found for log NT-proBNP (standardized regression coefficient 0.438, 95 confidence interval 0.350.53, P 0.001). Hierarchical clustering analysis demonstrated that UACR clusters with markers of congestion and less with indices of renal function. The validation cohort yielded similar findings.
In patients with new-onset or worsening heart failure, albuminuria is consistently associated with clinical, echocardiographic, and circulating biomarkers of congestion.
Nutritional disorders are frequent in patients with chronic pulmonary obstructive disease (COPD) and have negative health impacts. This study aimed to explore the value of the European Society of ...Clinical Nutrition and Metabolism (ESPEN) definition of malnutrition (and/or its individual components) to predict hospitalizations and mortality at 2 years, and to determine the prevalence of malnutrition in COPD patients referred to pulmonary rehabilitation.
The study was a prospective analysis of 118 patients with COPD free of exacerbations and/or hospital admissions in the previous two months. Main outcome variables were mortality, hospital admissions, and length of stay at 2-year follow-up; main covariates were malnutrition assessment according to the ESPEN definition and its components: unintentional weight loss, body mass index, and fat-free mass index (FFMI). Body composition was assessed by bioimpedance analysis. Kaplan-Meier survival curves and linear regression analyses were performed, adjusting for age and airflow obstruction as potential confounders.
The observed prevalence of malnutrition was 24.6%. Malnutrition was associated with increased mortality risk (HR = 3.9 95% CI: 1.4–10.62). FFMI was independently associated with increased mortality (HR = 17.0 95% CI: 2.24–129.8), which persisted after adjustment for age and lung function (adjusted HR = 13.0 95% CI: 1.67–101.7). Low age-related body mass index was associated with increased risk of hospital admissions.
Malnutrition according to ESPEN criteria, highly prevalent in patients with stable COPD referred to pulmonary rehabilitation, was associated with 4 times greater mortality risk after 2 years. Low FFMI was associated with a 17-fold increase in mortality risk, suggesting independent predictive value.
•The prevalence of malnutrition according to ESPEN criteria in patients with stable COPD was 24.6%.•Malnutrition is associated with 3.9-fold increased risk of mortality at 2-year follow-up.•Fat-free mass index was associated with 17 times greater risk of mortality, the highest factor of all ESPEN components.•Low age-related body mass index was the only component associated with increased risk of hospital admissions.
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