The Past and Future of Psychedelic Science: An Introduction to This Issue.

Psychedelic plants and fungi have been used in indigenous medicinal traditions for millennia. Modern psychedelic research began when Albert Hofmann first synthesized lysergic acid diethylamide (LSD-25) in 1938. Five years later, became the first person to ingest LSD. Hofmann was unaware of the significance of his actions, and the effects they would set in motion. After a burgeoning period of scientific and cultural exploration in the1950s and '60s, psychedelic research was slowed to a near halt. Throughout the 1970s and '80s governmental interventions severely hampered global psychedelic research, despite evidence of the limited medical risks and therapeutic potential of psychedelics. After decades of persistent education and advocacy, rigorous research employing psychedelics as tools of discovery and healing are abundant today. Studies are taking place in research institutions and in private practice sites supported by non-profit and for-profit organizations, as well as individual investigators. This research includes clinical trials with MDMA-assisted therapy for the treatment of PTSD, alcoholism, and social anxiety, and psilocybin clinical studies for depression and addiction, as well as the ability of psychedelics to catalyze spiritual or mystical experiences and inspire creativity, and into the neuroscientific understanding the effects of psychedelic substances on our nervous system.

Increased orosomucoid in urine is an independent predictor of cardiovascular and all-cause mortality in patients with type 2 diabetes at 10 years of follow-up.

AIMS: To evaluate whether increased urinary orosomucoid excretion rate (UOER) is an independent predictor of cardiovascular and all-cause mortality in type 2 diabetes (T2DM) and type 1 diabetes (T1DM) at 10years of follow-up. METHOD: We followed 430 patients with T2DM and 148 patients with T1DM until emigration, death or November 2011. We measured UOER levels in overnight urine samples. RESULTS: Descriptive data are given in the article. In patients with T2DM and T1DM, all-cause mortality (log-rank test, p<0.01 for both types) and cardiovascular mortality (log-rank test, p<0.01 for T2DM and p=0.04 for T1DM) were significantly higher in patients with increased UOER. Normoalbuminuric patients with T2DM and increased UOER levels had higher all-cause and cardiovascular mortality (log-rank test, p<0.01 for both types). UOER was independently predictive of all-cause (HR 1.52; 95% CI 1.10-2.09; p=0.01) and cardiovascular (HR 2.31; 95% CI 1.46-3.66; p<0.01) mortality in patients with T2DM, but not in patients with T1DM. CONCLUSION: UOER is an independent predictor of all-cause and cardiovascular mortality even in normoalbuminuric patients with T2DM at 10years of follow-up. Further studies are needed in order to evaluate the prognostic and clinical relevance.

Increased urinary orosomucoid excretion is not related to impaired renal function in patients with type 2 diabetes.

OBJECTIVES: Increased urinary orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes at 5-years of follow-up. To further explore UOER in relation to local renal physiological phenomena, we studied renal glomerular and tubular functions in patients with type 2 diabetes and normal or increased UOER. METHODS: We performed a cross-sectional study of 40 patients with type 2 diabetes (normal UOER, n=16; increased UOER, n=24) who displayed no signs of cardiovascular disease and 21 healthy control persons. The renal clearance values of [(51)Cr]ethylenediaminetetraacetic acid ([(51)Cr]EDTA), lithium, orosomucoid, albumin, and sodium were measured. RESULTS: Patients with type 2 diabetes had normal glomerular filtration rate (GFR) measured by [(51)Cr]EDTA clearance. The clearance value of orosomucoid was highly increased in patients with increased UOER. The clearance values of albumin were similar in patients with increased UOER and in healthy controls. Investigations of renal tubular function revealed normal and similar levels of lithium clearance and proximal and distal reabsorption of sodium and water. Serum values of orosomucoid were higher in patients with increased UOER than in healthy controls (P<.001), but were still within reference limits, suggesting chronic low-grade inflammation. UOER was associated with increasing values of orosomucoid clearance (P<.0001) independently of serum orosomucoid. CONCLUSIONS: Patients with type 2 diabetes and increased UOER had normal GFR and showed no signs of renal glomerular or tubular dysfunction. We therefore hypothesize that increased levels of UOER may be caused by local renal production of orosomucoid due to chronic low-grade inflammation.

Sub-acute neuropathy in patients with African tick bite fever.

African tick bite fever (ATBF) caused by Rickettsia africae is an emerging health problem in travellers to sub-Saharan Africa. We here present 6 patients with evidence of long-lasting sub-acute neuropathy following ATBF contracted during safari trips to southern Africa. Three patients developed radiating pain, paresthaesia and/or motor weakness of extremities, 2 had hemi-facial pain and paresthaesia, and 1 developed unilateral sensorineural hearing loss. When evaluated 3-26 months after symptom onset, cerebrospinal fluid samples from 5 patients were negative for R. africae PCR and serology, but revealed elevated protein content in 3 and mild pleocytosis in 1 case. Despite extensive investigations, no plausible alternative causes of neuropathy could be identified. Treatment with doxycycline in 2 patients had no clinical effect. Given the current increase of international safari tourism to sub-Saharan Africa, more cases of sub-acute neuropathy following ATBF may well be encountered in Europe and elsewhere in the y to come.

Monitoring urinary orosomucoid in acute inflammation: observations on urinary excretion of orosomucoid, albumin, alpha1-microglobulin, and IgG.

BACKGROUND: Inflammation-associated proteinuria in acute, nonrenal disease is a common but poorly understood phenomenon. We performed an observational study of the urinary excretion of orosomucoid (alpha(1)-acid glycoprotein), albumin, alpha(1)-microglobulin (protein HC), and IgG to obtain quantitative and temporal data on these 4 proteins. METHODS: Urine samples were collected at daily intervals for up to 23 days from 6 patients with surgery-induced inflammation and at hourly intervals for a 24-h period from 7 sepsis patients. Urinary protein concentrations were assessed by immunoturbidimetry. RESULTS: During surgery-induced inflammation, the increase and decrease in orosomucoid excretion mirrored changes in plasma C-reactive protein. Values for all 4 urinary proteins were increased in sepsis patients. The observed maximum increases in urinary protein excretion relative to the upper reference values were 280-fold for orosomucoid, 98-fold for alpha(1)-microglobulin, 33-fold for albumin, and 26-fold for IgG. CONCLUSIONS: Orosomucoid, usually present in plasma and urine in much lower concentrations than albumin, is increased in urine to concentrations equal to or higher than albumin in proteinuria associated with acute inflammation. The pathophysiologic mechanisms responsible for this markedly increased excretion are unknown. Monitoring of urinary excretion of orosomucoid and other specific proteins, expressed as protein/creatinine ratios, may provide a window for clinically relevant real-time observation of changes in acute inflammatory processes. Orosomucoid in urine may be a more informative marker than albumin for inflammation.

A particle-enhanced turbidimetric immunoassay for quantitative determination of orosomucoid in urine: development, validation and reference values.

Increased urinary orosomucoid excretion rate (UOER) is an independent predictor of cardiovascular and all-cause mortality in patients with type 2 diabetes, as demonstrated by a conventional, immunoturbidimetric method. We wanted to optimize the method by developing a fully automated, particle-enhanced turbidimetric (PET) immunoassay with a lower detection limit, to allow assessment of orosomucoid in urine in healthy individuals and patients. A micro-particle-based immunoreagent was prepared for a PET immunoassay. The calibration was traceable to the certified reference material (CRM 470) for specific human serum proteins. We studied 69 healthy adults (28 men and 41 women) to establish reference values for the new assay. The detection limit of orosomucoid in urine was found to be 0.05 mg/l, about 20 times lower than for the conventional assay. Within-run imprecision [CV%, (level)] was 6.7% (0.23 mg/l), 1.0% (1.08 mg/l) and 1.0% (4.69 mg/l). Total imprecision [CV%, (level)] was 10.4% (0.23 mg/l), 3.9% (1.08 mg/l) and 3.4% (4.69 mg/l). Reference values [median (2.5-97.5 percentiles)] for UOER were 0.36 (0.07-2.04) microg/min and for urinary orosomucoid/creatinine ratio 0.04 (0.009-0.17) mg/mmol. We describe a fully automated, transferable, sufficiently precise, high-sensitivity assay for orosomucoid in urine and present reference values traceable to CRM 470.

Orosomucoid in urine predicts cardiovascular and over-all mortality in patients with Type II diabetes.

AIMS/HYPOTHESIS: Urinary orosomucoid excretion rate is increased in a substantial proportion of patients with Type II (non-insulin-dependent) diabetes mellitus and normal urinary albumin excretion rate. The aim of this study was to determine whether increased urinary orosomucoid excretion rate is predictive of increased mortality in patients with Type II diabetes. METHODS: In a cohort study including 430 patients with Type II diabetes, baseline urinary samples were analysed for orosomucoid and albumin. Mean follow-up was 2.4 years. RESULTS: We found that 188 (44 %) patients had normal and 242 (56 %) patients had increased urinary orosomucoid excretion rates. During the study period 41 patients died; out of these 23 patients died of cardiovascular diseases. Odds ratio for all-cause mortality was 2.50 (95 % CI 1.00-6.22) and odds ratio for cardiovascular mortality was 9.81 (1.31-73.6) having increased urinary orosomucoid excretion rate at baseline (odds ratios adjusted for age, sex, duration of diabetes, cardiovascular diseases, weight, medication, HbA1 c, plasma creatinine and urinary albumin excretion rate). Urinary albumin excretion rate was an independent predictor of all-cause mortality when urinary orosomucoid excretion rate was not included in the analysis. Subgroup analysis revealed that 39 % of the patients with normal urinary albumin excretion rate (n = 251) had increased urinary orosomucoid excretion rates and that these patients had a higher cardiovascular mortality (p = 0.007) than patients with normal urinary albumin excretion rate and normal urinary orosomucoid excretion rates. CONCLUSION/INTERPRETATION: We found that urinary orosomucoid excretion rate predicted all-cause and cardiovascular mortality in patients with Type II diabetes independently from other risk factors.