Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans

Recently, the anti-addictive potential of ayahuasca, a dimethyltryptamine(DMT)- and β-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of the Northwest Amazon and currently by syncretic churches worldwide, has received increased attention. To better evaluate this topic, we performed a systematic literature review using the PubMed database to find quantitative studies (using statistical analysis) that assessed the effects of ayahuasca or its components in drug-related symptoms or disorders. We found five animal studies (using harmaline, harmine, or ayahuasca) and five observational studies of regular ayahuasca consumers. All animal studies showed improvement of biochemical or behavioral parameters related to drug-induced disorders. Of the five human studies, four reported significant reductions of dependence symptoms or substance use, while one did not report significant results. The mechanisms responsible for the anti-addictive properties of ayahuasca and its alkaloids are not clarified, apparently involving both peripheral MAO-A inhibition by the β-carbolines and central agonism of DMT at 5-HT2A receptors expressed in brain regions related to the regulation of mood and emotions. Although results are promising, controlled studies are needed to replicate these preliminary findings.     

Dietary total antioxidant capacity is associated with plasmatic antioxidant capacity,nutrient intake and lipid and DNA damage in healthy women

Dietary total antioxidant capacity (DTAC) seems to be associated with reducing risk of diseases. However, data about the influence of the DTAC on oxidative stress parameters are scarce. The aim of this study was to estimate the DTAC and its influence on plasma total antioxidant capacity (PTAC), and damage to lipids, proteins and DNA in healthy women. It was found a positive correlation between DTAC and PTAC in young and healthy subjects, where presumably the endogenous defenses are fully functional. DTAC and PTAC were positively correlated with the intake of known antioxidants, including vitamin C and polyphenols. The DTAC exhibited a negative correlation with lipid oxidative damage, while PTAC showed a negative correlation with DNA damage. This data contributes to better understanding of the recommended dietary antioxidant intake for promoting health.     

Inflammatory biomarkers in infective endocarditis: machine learning to predict mortality

Infective endocarditis (IE) is the cardiac disease with the highest rates of mortality. New biomarkers that are able to identify patients at risk for death are required to improve patient management and outcome. This study aims to investigate if cytokines, chemokines and growth factors measured at IE diagnosis can predict mortality. Patients with definite IE, according to the Duke’s modified criteria, were included. Using high-performance Luminex assay, 27 different cytokines, chemokines and growth factors were analyzed. Machine learning techniques were used for the prediction of death and subsequently creating a decision tree, in which the cytokines, chemokines and growth factors were analyzed together with C-reactive protein (CRP). Sixty-nine patients were included, 41 (59%) male, median age 54 [interquartile range (IQR) = 41–65 years] and median time between onset of the symptoms and diagnosis was 12 days (IQR = 5–30 days). The in-hospital mortality was 26% (n = 18). Proinflammatory cytokines interkeukin (IL)-15 and C-C motif chemokine ligand (CCL4) were found to predict death, adding value to CRP levels. The decision tree predicted correctly the outcome of 91% of the patients at hospital admission. The high-risk group, defined as CRP ≥ 72 mg/dL, IL-15 ≥ 5·6 fg/ml and CCL4 ≥ 6·35 fg/ml had an 88% in-hospital mortality rate, whereas the patients classified as low-risk had a mortality rate of 8% (P = < 0·001). Cytokines IL-15 and CCL4 were predictors of mortality in IE, adding prognostic value beyond that provided by CRP levels. Assessment of cytokines has potential value for clinical risk stratification and monitoring in IE patients.     

Calcium hydroxide barrier over the apical root-end of a type III dens invaginatus after endodontic and surgical treatment

AIM: To report the simultaneous endodontic and surgical treatment of a tooth associated with Oehlers type III dens invaginatus and a persistent periapical lesion, which comprised root-end resection, root-end filling and application of a calcium hydroxide barrier placed on the resected dentine surface. SUMMARY: Three root canals were identified in a tooth with a type III dens invaginatus, which presented with a necrotic pulp, wide foraminal opening and extensive periapical lesion, and with a previous history of acute abscess, intracanal exudate and fistula. After root canal preparation followed by intracanal application of calcium hydroxide pastes, the clinical-pathological status persisted. After periapical curettage and root-end resection, the root canals were filled, followed by root-end filling with Sealer 26 mixed with zinc oxide powder to a clay-like consistency. Calcium hydroxide paste was then applied over the exposed dentinal surface forming a covering over the root apex. At the 20-month follow-up examination the patient had no symptoms and no fistula; advanced periapical bone repair was obvious on the radiograph. KEY LEARNING POINTS: Because of the variable morphology and extent of invagination, type III dens invaginatus represents a challenge for conventional treatment, often leading to the need for a surgical approach. Sealer 26 thickened with zinc oxide powder provided satisfactory clinical properties for use as a root-end filling material. Application of a calcium hydroxide barrier over the resected root-end is a potential treatment option to encourage tissue repair.     

A Descriptive Analysis of the Relationships Between Social Context,Engagement and Stereotypy in Residential Services for People with Severe and Complex Disabilities

Observational data on 40 people with severe intellectual disabilities and sensory impairments were analysed to determine the relationship between user engagement, stereotypy and the nature of staff support received. The results indicated that (1) practical support was associated with an increased probability of engagement for 94% and decreased stereotypy for 98% of participants; (2) other forms of contact were associated with a decreased probability of engagement for 77% and decreased stereotypy for 79% of participants; (3) episodes of no contact were associated with significantly elevated rates of stereotypy in all participants; (4) practical support was significantly more likely to be associated with an increase in the odds of engagement than either no contact or other forms of contact; (5) no contact was significantly more likely to be associated with an increase in the odds of stereotypy than either practical support or other forms of contact; (6) practical support appeared to have more impact on engagement in less institutionalised services, services which experienced lower rates of staff sickness, and in services which provided more regularly scheduled social activities.     

Evidence for widespread infection of wild rats with hepatitis E virus in the United States.

Hepatitis E is an important medical pathogen in many developing countries but is rarely reported from the United States, although antibody to hepatitis E virus (anti-HEV) is found in > 1% of U.S. citizens. Zoonotic spread of the virus is suspected. Sera obtained from 239 wild rats trapped in widely separated regions of the United States were tested for anti-HEV. Seventy-seven percent of rats from Maryland, 90% from Hawaii, and 44% from Louisiana were seropositive for anti-HEV. Rats from urban as well as rural areas were seropositive and the prevalence of anti-HEV IgG increased in parallel with the estimated age of the rats, leading to speculation that they might be involved in the puzzling high prevalence of anti-HEV among some U.S. city dwellers. The discovery of a in rats in the United States and the recently reported discovery that HEV is endemic in U.S. swine raise many questions about transmission, reservoirs, and strains of HEV in developed countries.     

High prevalence of TT virus (TTV) infection in patients on maintenance hemodialysis: frequent mixed infections with different genotypes and lack of evidence of associated liver disease.

Recently, a novel DNA virus, TT virus (TTV), was identified in patients with post-transfusion non-A-G hepatitis. We analyzed the prevalence and clinical implications of TTV infection in a cohort of 96 Spanish patients on long-term hemodialysis. TTV DNA was detected by nested PCR in 51 (53%) of 96 patients, a prevalence significantly higher than that found in healthy blood donors. Persistent liver test abnormalities were found in only 2 (7.7%) of 26 patients infected with TTV alone, compared with 12 (75%) of 16 patients infected with hepatitis C or hepatitis B virus, or both (P < 0.01). Mixed infections with multiple strains of TTV, including different major genotypes, were common in patients on hemodialysis. These patients had received a significantly greater number of blood units (22.7 +/- 20) compared with patients apparently infected with a single strain of TTV (8.9 +/- 11) (P = 0.01). Phylogenetic analyses of TTV from infected patients identified strains of genotypes 1, 2, 3, and 4. In summary, TTV infection was common in patients on hemodialysis but was not associated with liver disease     

Endogenous nitric oxide acts as a natural antithrombotic agent in vivo by inhibiting platelet aggregation in the pulmonary vasculature.

Nitric oxide (NO) is a powerful vasodilator and an inhibitor of platelet aggregation in vitro. While the ability of NO to modulate vascular tone in vivo has been proven, only a few studies have assessed its platelet inhibitory activity in vivo. We have employed two complementary animal models of pulmonary platelet thromboembolism to assess the antithrombotic activity of endogenous NO in vivo. The inhibition of nitric oxide synthase (NOS) by L-NAME significantly potentiated while the administration of the NOS substrate L-arginine significantly reduced the accumulation of 111In-labelled platelets in the pulmonary vasculature of rabbits induced by intravenous collagen plus epinephrine. L-NAME or L-arginine did not, however, modify 111In-labelled erythrocyte distribution in lungs and phenylephrine had no effect on platelet accumulation following collagen + adrenaline, suggesting that the effects of L-NAME were not due to vasoconstriction but rather to a direct modification of platelet function. In mice, L-NAME significantly reduced the dose of collagen + adrenaline required to induce thromboembolic mortality, increased the fall in circulating platelets and increased the % of pulmonary vessels occluded by platelet thrombi. The effects of L-NAME were reversed by L-arginine but not by a dose of nicardipine exerting maximal vasodilatation. Phenylephrine did not potentiate collagen + adrenaline-induced mortality. In the pulmonary vasculature in vivo, endogenous NO inhibits collagen + adrenaline-induced aggregation and enhances platelet disaggregation. This natural modulator function of NO is exerted via a direct effect on platelets and not as a result of haemodynamic changes.