Monoamine Oxidase Inhibition by Plant-Derived β-Carbolines; Implications for the Psychopharmacology of Tobacco and Ayahuasca

The monoamine oxidases (MAOs) are flavin-containing amine oxidoreductases responsible for metabolism of many biogenic amine molecules in the brain and peripheral tissues. Whereas serotonin is the preferred substrate of MAO-A, phenylethylamine is metabolized by MAO-B, and dopamine and tyramine are nearly ambivalent with respect to the two isozymes. β-Carboline alkaloids such as harmine, harman(e), and norharman(e) are MAO inhibitors present in many plant materials, including foodstuffs, medicinal plants, and intoxicants, notably in tobacco (Nicotiana spp.) and in Banisteriopsis caapi, a vine used in the Amazonian ayahuasca brew. The β-carbolines present in B. caapi may have effects on neurogenesis and intrinsic antidepressant properties, in addition to potentiating the bioavailability of the hallucinogen N,N-dimethyltryptamine (DMT), which is often present in admixture plants of ayahuasca such as Psychotria viridis. Tobacco also contains physiologically relevant concentrations of β-carbolines, which potentially contribute to its psychopharmacology. However, in both cases, the threshold of MAO inhibition sufficient to interact with biogenic amine neurotransmission remains to be established. An important class of antidepressant medications provoke a complete and irreversible inhibition of MAO-A/B, and such complete inhibition is almost unattainable with reversible and competitive inhibitors such as β-carbolines. However, the preclinical and clinical observations with synthetic MAO inhibitors present a background for obtaining a better understanding of the polypharmacologies of tobacco and ayahuasca. Furthermore, MAO inhibitors of diverse structures are present in a wide variety of medicinal plants, but their pharmacological relevance in many instances remains to be established. Keywords: Banisteriopsis caapi; Nicotiana; ayahuasca; dimethyltryptamine (DMT); harmine; monoamine oxidase (MAO); tobacco; β-carbolines

Monoamine Oxidase Inhibition by Plant-Derived β-Carbolines; Implications for the Psychopharmacology of Tobacco and Ayahuasca.

The monoamine oxidases (MAOs) are flavin-containing amine oxidoreductases responsible for metabolism of many biogenic amine molecules in the brain and peripheral tissues. Whereas serotonin is the preferred substrate of MAO-A, phenylethylamine is metabolized by MAO-B, and dopamine and tyramine are nearly ambivalent with respect to the two isozymes. β-Carboline alkaloids such as harmine, harman(e), and norharman(e) are MAO inhibitors present in many plant materials, including foodstuffs, medicinal plants, and intoxicants, notably in tobacco (Nicotiana spp.) and in Banisteriopsis caapi, a vine used in the Amazonian ayahuasca brew. The β-carbolines present in B. caapi may have effects on neurogenesis and intrinsic antidepressant properties, in addition to potentiating the bioavailability of the hallucinogen N,N-dimethyltryptamine (DMT), which is often present in admixture plants of ayahuasca such as Psychotria viridis. Tobacco also contains physiologically relevant concentrations of β-carbolines, which potentially contribute to its psychopharmacology. However, in both cases, the threshold of MAO inhibition sufficient to interact with biogenic amine neurotransmission remains to be established. An important class of antidepressant medications provoke a complete and irreversible inhibition of MAO-A/B, and such complete inhibition is almost unattainable with reversible and competitive inhibitors such as β-carbolines. However, the preclinical and clinical observations with synthetic MAO inhibitors present a background for obtaining a better understanding of the polypharmacologies of tobacco and ayahuasca. Furthermore, MAO inhibitors of diverse structures are present in a wide variety of medicinal plants, but their pharmacological relevance in many instances remains to be established

United States Response to Questionnaire Concerning \u3cem\u3eCopyright, Competition and Innovation\u3c/em\u3e

ALAI-USA is the U.S. branch of ALAI (Association Littèraire et Artistique Internationale). ALAI-USA was started in the 1980\u27s by the late Professor Melville B. Nimmer, and was later expanded by Professor John M. Kernochan

Low Self-Reported Physical Function Status Was an Excellent Predictor of Adverse Postoperative Course in Older Veterans Having Knee and Hip Surgery

Objectives: To measure the association between functional status and an adverse postoperative course. Design: Retrospective cohort study. Setting: Veterans Affairs Medical Center. Participants: Older adults who underwent total hip and knee replacement (THR and TKR) at a VA facility from 2002-2009. To be included, subjects must have completed the Veteran Rand-12 (VR-12) within six months of surgery. VR-12 is a general purpose 12 item health quality survey nearly identical to the SF-12 for which the summary score of physical health called physical component score (PCS) is normed to a value of 50 for US adults with standard deviation of 10. Measurements: We measured the association of PCS split into quartiles with the outcomes major complication (cardiac arrest, myocardial infarction, stoke, respiratory failure, pneumonia, pulmonary embolism, sepsis, and renal failure), discharge to nursing home, and readmission. We checked our association for confounding by age, race, surgery type, facility volume, duration of time between collection of PCS and surgery, and clustering by facility. Results: We identified 3,542 THR and TKR surgeries for which PCS information was available. The very lowest quartile of PCS (values 4.9-24.2) predicted a 2.7 fold increase in odds of major complications, 2.1 fold increase in odds of discharge to nursing home, and a 1.9 fold increase in odds of readmission compared with highest quartile (PCS 38.9-61). The next lowest quartile (PCS 24.3-31.8) also predicted elevated rates of major complication and readmission. Conclusions: Very low PCS predicts greater than a 2 fold increase in major complication and readmission after total hip and knee replacement. Future research should re-measure the effect of very low PCS in populations not addressed by our study including women, patients having non-orthopedic surgery, and nonveterans

Splenic infarction: an update on William Osler\u27s observations.

BACKGROUND: Osler taught that splenic infarction presents with left upper abdominal quadrant pain, tenderness and swelling accompanied by a peritoneal friction rub. Splenic infarction is classically associated with bacterial endocarditis and sickle cell disease. OBJECTIVES: To describe the contemporary experience of splenic infarction. METHODS: We conducted a chart review of inpatients diagnosed with splenic infarction in a Jerusalem hospital between 1990 and 2003. RESULTS: We identified 26 cases with a mean age of 52 years. Common causes were hematologic malignancy (six cases) and intracardiac thrombus (five cases). Only three cases were associated with bacterial endocarditis. In 21 cases the splenic infarction brought a previously undiagnosed underlying disease to attention. Only half the subjects complained of localized left-sided abdominal pain, 36% had left-sided abdominal tenderness; 31% had no signs or symptoms localized to the splenic area, 36% had fever, 56% had leukocytosis and 71% had elevated lactate dehydrogenase levels. One splenectomy was performed and all patients survived to discharge. A post hoc analysis demonstrated that single infarcts were more likely to be associated with fever (20% vs. 63%, p \u3c 0.05) and leukocytosis (75% vs. 33%, P = 0.06) CONCLUSIONS: The clinical presentation of splenic infarction in the modern era differs greatly from the classical teaching, regarding etiology, signs and symptoms. In patients with unexplained splenic infarction, investigation frequently uncovers a new underlying diagnosis

A systematic review of mobility instruments and their measurement properties for older acute medical patients

<p>Abstract</p> <p>Background</p> <p>Independent mobility is a key factor in determining readiness for discharge for older patients following acute hospitalisation and has also been identified as a predictor of many important outcomes for this patient group. This review aimed to identify a physical performance instrument that is not disease specific that has the properties required to accurately measure and monitor the mobility of older medical patients in the acute hospital setting.</p> <p>Methods</p> <p>Databases initially searched were Medline, Cinahl, Embase, Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials without language restriction or limits on year of publication until July 2005. After analysis of this yield, a second step was the systematic search of Medline, Cinahl and Embase until August 2005 for evidence of the clinical utility of each potentially suitable instrument. Reports were included in this review if instruments described had face validity for measuring from bed bound to independent levels of ambulation, the items were suitable for application in an acute hospital setting and the instrument required observation (rather than self-report) of physical performance. Evidence of the clinical utility of each potentially suitable instrument was considered if data on measurement properties were reported.</p> <p>Results</p> <p>Three instruments, the Elderly Mobility Scale (EMS), Hierarchical Assessment of Balance and Mobility (HABAM) and the Physical Performance Mobility Examination (PPME) were identified as potentially relevant. Clinimetric evaluation indicated that the HABAM has the most desirable properties of these three instruments. However, the HABAM has the limitation of a ceiling effect in an older acute medical patient population and reliability and minimally clinically important difference (MCID) estimates have not been reported for the Rasch refined HABAM. These limitations support the proposal that a new mobility instrument is required for older acute medical patients.</p> <p>Conclusion</p> <p>No existing instrument has the properties required to accurately measure and monitor mobility of older acute medical patients.</p

Within-treatment changes in a novel addiction treatment program using traditional Amazonian medicine

Aims: The therapeutic use of psychedelics is regaining scientific momentum, but similarly psychoactive ethnobotanical substances have a long history of medical (and other) uses in indigenous contexts. Here we aimed to evaluate patient outcomes in a residential addiction treatment center that employs a novel combination of Western and traditional Amazonian methods. Methods: The study was observational, with repeated measures applied throughout treatment. All tests were administered in the center, which is located in Tarapoto, Peru. Data were collected between 2014 and 2015, and the study sample consisted of 36 male inpatients who were motivated to seek treatment and who entered into treatment voluntarily. Around 58% of the sample was from South America, 28% from Europe, and the remaining 14% from North America. We primarily employed repeated measures on a psychological test battery administered throughout treatment, measuring perceived stress, craving frequency, mental illness symptoms, spiritual well-being, and physical and emotional health. Addiction severity was measured on intake, and neuropsychological performance was assessed in a subsample from intake to at least 2 months into treatment. Results: Statistically significant and clinically positive changes were found across all repeated measures. These changes appeared early in the treatment and were maintained over time. Significant improvements were also found for neuropsychological functioning. Conclusion: These results provide evidence for treatment safety in a highly novel addiction treatment setting, while also suggesting positive therapeutic effects

Long-term change in respiratory function following spinal cord injury.

STUDY DESIGN: Retrospective study. OBJECTIVES: To model the effect of time since injury on longitudinal respiratory function measures in spinal cord injured-individuals and to investigate the effect of patient characteristics. SETTING: A total of 173 people who sustained a spinal cord injury between 1966 and April 2013 and who had previously participated in research or who underwent clinically indicated outpatient respiratory function tests at the Austin Hospital in Melbourne, Australia, were included in the study. At least two measurements over time were available for analysis in 59 patients. METHODS: Longitudinal data analysis was performed using generalised linear regression models to determine changes in respiratory function following spinal cord injury from immediately post injury to many years later. Secondly, we explored whether injury severity, age, gender and body mass index (BMI) at injury altered the time-dependent change in respiratory function. RESULTS: The generalised linear regression model showed no significant change (P=0.276) in respiratory function measured in (forced) vital capacity ((F)VC) after the spinal cord injury. However, significant (P30 kg m(-2).Spinal Cord advance online publication, 12 January 2016; doi:10.1038/sc.2015.233

Feasibility and impact of a post–discharge geriatric evaluation and management service for patients from residential care: the Residential Care Intervention Program in the Elderly (RECIPE)

BackgroundGeriatric evaluation and management has become standard care for community dwelling older adults following an acute admission to hospital. It is unclear whether this approach is beneficial for the frailest older adults living in permanent residential care. This study was undertaken to evaluate (1) the feasibility and consumer satisfaction with a geriatrician-led supported discharge service for older adults living in residential care facilities (RCF) and (2) its impact on the uptake of Advanced Care Planning (ACP) and acute health care service utilisation.MethodsIn 2002&ndash;4 a randomised controlled trial was conducted in Melbourne, Australia comparing the geriatrician&ndash;led outreach service to usual care for RCF residents. Patients were recruited during their acute hospital stay and followed up at the RCF for six months. The intervention group received a post-discharge home visit within 96 hours, at which a comprehensive geriatric assessment was performed and a care plan developed. Participants and their families were also offered further meetings to discuss ACPs and document Advanced Directives (AD). Additional reviews were made available for assessment and management of intercurrent illness within the RCF. Consumer satisfaction was surveyed using a postal questionnaire.ResultsThe study included 116 participants (57 intervention and 59 controls) with comparable baseline characteristics. The service was well received by consumers demonstrated by higher satisfaction with care in the intervention group compared to controls (95% versus 58%, p&thinsp;=&thinsp;0.006).AD were completed by 67% of participants/proxy decision makers in the intervention group compared to 13% of RCF residents prior to service commencement. At six months there was a significant reduction in outpatient visits (intervention 21 (37%) versus controls 45 (76%), (p&thinsp;&lt;&thinsp;0.001), but no difference in readmissions rates (39% intervention versus 34% control, p&thinsp;=&thinsp;0.6). There was a trend towards reduced hospital bed-day utilisation (intervention 271 versus controls 372 days).ConclusionIt is feasible to provide a supported discharge service that includes geriatrician assessment and care planning within a RCF. By expanding the service there is the potential for acute health care cost savings by decreasing the demand for outpatient consultation and further reducing acute care bed-days.<br /