Portable gamma-camera for the diagnosis of brain death diagnosis. / Minigammacámara portátil para el diagnóstico de muerte encefálica.

OBJECTIVE: To evaluate the feasibility of using the Sentinella® portable gamma-camera for the diagnosis of brain death (BD). DESIGN: A prospective, observational feasibility study was carried out. SETTING: Intensive Care Unit of a third level hospital. PATIENTS: Consecutive recording was made of the adults diagnosed with brain death based on clinical criteria following admission to the Intensive Care Unit in the period from January to December 2017. INTERVENTIONS: The procedure was performed at the patient bedside with the intravenous administration of technetium 99 metastable hexamethylpropylene amine oxime. The absence of perfusion in the cerebral hemispheres and brainstem was described as a pattern consistent with BD. The diagnosis was correlated to the transcranial Doppler and / or electroencephalographic findings. RESULTS: A total of 66.1% of the patients were men with an average age of 60 years [IQR: 51-72]. The most frequent causes resulting in BD were hemorrhagic stroke (48.2%, n=27), followed by traumatic brain injury (30.4%, n=17), ischemic stroke (10.7%, n=6) and post-cardiac arrest anoxic encephalopathy (7.1%, n=4). A clinical diagnosis of BD was made in all cases, and the portable gamma-camera confirmed the diagnosis in 100% of the patients with a pattern characterized by the absence of brain perfusion. In addition, the results were compared with the transcranial Doppler findings in 46 patients, confirming the presence of diastolic reverberation and / or systolic peaks. The electroencephalographic tracing was obtained in 10 cases, with the appearance of electrical silence, due to the absence of an acoustic window in the transcranial Doppler study. CONCLUSIONS: A portable gamma-camera could be a useful and feasible tool for the diagnosis of BD.

In vitro activity of uva-ursi against cytochrome P450 isoenzymes and P-glycoprotein.

Some natural health products (NHPs) affect drug metabolism enzymes and transport proteins, potentially affecting the safety and efficacy of the drug or other NHPs. This study was undertaken to characterize the effect of uva-ursi (Arctostaphylos uva-ursi) on cytochrome P450 isozyme (3A4, 3A5, 3A7, 2C19, and 19)-mediated metabolism and P-glycoprotein (P-gp) transport. Three bulk and 2 capsulated uva-ursi samples were obtained from commercial outlets. The capsules were batched, and herbal samples were ground to a common consistency. Aqueous and methanol extracts were freshly prepared. Cytochrome P450 isozyme-mediated metabolism was determined by using in vitro bioassays. P-gp transport function was determined by using a rhodamine 123 (Rh123) uptake test in human (THP-1) monocytes and human Caco-2 cells. All products were analyzed by HPLC for arbutin, gallic acid, myricitrin, and isoquercetin. A large variation was observed in the biomarkers found between the bulk and capsulated samples. Our data indicate that both the aqueous and methanol extracts of all 5 uva-ursi products showed high cytochrome P450 isozyme inhibition, with the exception of the methanol extracts against cytochromes P3A4 and P19, which had low to moderate activity. The aqueous extracts of uva-ursi showed an inhibitory effect on Rh123 efflux by P-gp at 1 h and an inductive effect at 18 h for both cell lines. Our results show that the uva-ursi herbal products tested here have pharmacological properties, including the potential capacity to affect drug safety and efficacy. Further studies are warranted against a wider range of cytochrome P450 isozymes and to determine whether these effects are clinically significant.

Pharmacokinetics, metabolism and toxicity of the plant-derived photoxin alpha-terthienyl.

The plant-derived insecticide, alpha-terthienyl was prepared by synthesis as 3',4'-di[14C]-alpha-terthienyl for pharmacokinetic and metabolism studies. When administered orally to rats at a single dose of 50 mg/kg, excretion of the labelled material was maximal one day after administration and declined to no measurable quantities by day 4. Two metabolites [1,4-di(2'-thienyl)1,4-butadione and 2-2'-bithiophene-5-carboxylic acid] and trace quantities of the parent material were isolated from the urine and chemically identified. These represent the first metabolites of alpha-terthienyl identified. In pilot acute and subacute trials, unlabelled alpha-terthienyl was non-toxic when administered orally to rats as the "ready to use" formulation (0.1% active ingredient). The pure compound had an LD50 of 110 mg/kg when administered intraperitoneally to rats. The results suggest that there is considerable separation with respect to mosquito larvae and non-target mammal sensitivity.

Antidiabetic plants and their active constituents.

Diabetes mellitus is a debilitating and often life-threatening disease with increasing incidence in rural populations throughout the world. A scientific investigation of traditional herbal remedies for diabetes may provide valuable leads for the development of alternative drugs and therapeutic strategies. Alternatives are clearly needed because of the inability of current therapies to control all of the pathological aspects of diabetes, and the high cost and poor availability of current therapies for many rural populations, particularly in developing countries. This review provides information on more than 1200 species of plants reported to have been used to treat diabetes and/or investigated for antidiabetic activity, with a detailed review of representative plants and some of great diversity of plant constituents with hypoglycemic activity, their mechanisms of action, methods for the bioassay of hypoglycemic agents, potential toxicity problems, and promising directions for future research on antidiabetic plants. The objective of this work is to provide a starting point for programs leading to the development of indigenous botanical resources as inexpensive sources for standardized crude or purified antidiabetic drugs, and for the discovery of lead compounds for novel hypoglycemic drug development.

Photoactive terthiophenes: the influence of serum on anti-HIV (human immunodeficiency virus) activities.

A number of carboxylic acid derivatives of the photoactive terthiophene, alpha-terthienyl, were found to possess impressive UVA-dependent activity against the human immunodeficiency virus, HIV-1; but only when assayed in the absence of serum, indicating that the latter contained interfering components. Good antiviral activity required a high rate of singlet oxygen production, in accordance with previous observations on thiophenes.

The anti-HIV activities of photoactive terthiophenes.

Various synthetic analogues of the naturally occurring terthiophene, alpha-terthienyl (alpha T), were evaluated for anti-human immunodeficiency virus (HIV) activity. The compounds were incubated individually with a known amount of the virus, with or without UVA radiation (long-wavelength ultraviolet) and residual virus was monitored for its ability to produce cytopathic effects in cell culture and the production of virus-specific protein (p24). The basic terthiophene structure was essential for good anti-HIV activity, although various side chains, such as alcohols, bromo, methyl, thiomethyl and trimethylsilyl groups, permitted retention of maximum activity. Under optimum conditions, as little as 12 ng/mL of these compounds (i.e. approximately 3 x 10(-8) M) could inactivate 10(3) infectious virions. None of the compounds however were more active than alpha T itself. In all cases, UVA radiation was essential. Several side chains decreased the antiviral efficacy, and some side chains abrogated the activity.

Structure-activity studies of photoactivated antiviral and cytotoxic tricyclic thiophenes.

The photoactivated antiviral and cytotoxic activities of the naturally occurring thiophene, alpha-terthienyl (1), and 15 synthetic analogues were evaluated against murine cytomegalovirus and Sindbis virus, and murine mastocytoma cells. After irradiation with near UV light, alpha-terthienyl and most of its analogues had significant toxicity, with minimum inhibitory concentrations in the range of 0.02-40 microM. In the absence of near UV irradiation, only one analogue had antiviral activity and five were cytotoxic. The most active analogues were those containing carboxylic acid, hydroxyl, or cyano substituents. Quantitative structure-activity relationship analysis of thiophene phototoxicity suggested that the rate of singlet oxygen production is the primary determinant of antiviral and cytotoxic activities. For phototoxicity against murine cytomegalovirus, a significant role for hydrophobicity was also demonstrated. Tricyclic thiophenes show significant potential for photochemotherapy of viral infections and cancer, and further evaluation in animal models is recommended.

A bioassay for inhibition of serotonin release from bovine platelets.

A bioassay was developed to study agents capable of inhibiting the release of serotonin from bovine blood platelets. It is a simple, inexpensive, and reproducible high-throughput bioassay suitable for quality control of feverfew, Tanacetum parthenium, a crude drug with proven migraine prophylactic activity that is being considered for governmental registration and regulation. The bioassay, which requires no experimental animals or human subjects, was used to assess the in vitro activity of T. parthenium samples grown from seed obtained from 10 different regions of Europe. The activity was found to vary significantly within and between samples, with no geographical correlation. Serotonin release inhibition was shown to be significantly correlated with the content of the germacranolide sesquiterpene lactone, parthenolide, although other sesquiterpene lactones from this plant and other members of the Asteraceae were also shown to be active. The activities of six other species of Tanacetum, as well as of Artemisia absinthium (wormwood) and Zingiber officinale (ginger), and two commercial drugs for migraine prophylaxis, verapamil hydrochloride and propranolol hydrochloride, were also assessed. The relevance of the bovine platelet serotonin release inhibition bioassay to antimigraine research is discussed.