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Biomedical subjects

N Lander

Publications and source records attributed to N Lander.

At least 19 recordsLinked to original sources

Current perceptions of Canadian autologous blood donors.

BACKGROUND AND OBJECTIVES: We determined the perceptions and motivations of autologous donors to establish their regard for this process and the new blood system established in 1999 in Canada. MATERIALS AND METHODS: Patients were surveyed before and after orthopaedic, cardiac, urological or gynecological procedures. RESULTS: Patients (n = 100; 57 men and 43 women) ranged in age from 19 to 83 years. Most had finished high school, and 21 had a university degree. Eighty-four had undergone previous surgery and 27 a previous transfusion. Fifty-one had been blood donors and 17 had been autologous donors. Specialists suggested donation to 78 of the patients. Seventy-two participated because they knew that their blood would be there. Three had a mistrust of the blood provider. Sixty-six believed that there is still a risk of receiving contaminated blood. Sixty-nine thought any risk was > or = 1 in 100,000; however, 16 thought the risk was < 1 in 1000. Postsurgery, 83 were happy to have donated their blood and 77 would do it again. Many felt that it improved their outcome. Most felt an increased sense of safety. Eighty-three patients were confident that the Canadian blood system had improved, but 17 were unsure. CONCLUSIONS: Concern about the safety of the allogeneic blood supply still drives the wish to autodonate. The process gives patients a sense of control and security. A large proportion of people felt that the Canadian blood system had improved, as determined by this 2003 study.

Adult↗

Perceptions and motivations of Canadian autologous blood donors.

Preoperative autologous blood donation in Canada has increased in the last decade due to concerns about allogeneic blood safety. As economic policies necessitate the validation of autologous blood donation, it is important to assess potential changes. This study examines the motivations and perceptions of patients participating in a Canadian autologous blood donation programme. The study was conducted at the Ottawa Hospital, Civic Campus. Questionnaires were developed and then administered to 100 consecutive adult autologous blood donors. The questionnaires assessed patient demographics, motivation for participation and perceptions about blood safety. Autologous donation was presented to 82% of patients as an option by their physicians. However, 59% of all patients felt that they were motivated to donate by their own fears. Patients (87%) also felt that directed blood donation should be offered due to their perception that directed donation is safer. Three-quarters of patients would be willing to pay for autologous donation. Patients are concerned about the safety of allogeneic blood and they are motivated to seek other alternatives despite the fact that allogeneic blood is very safe. These perceptions and motivations must be taken into account as health care policy changes are considered.

Adolescent↗

Enantiomeric cannabinoids: stereospecificity of psychotropic activity.

The 1,1-dimethylheptyl homolog of (-)-(3R,4R)-7-hydroxy-delta-6- tetrahydrocannabinol (compound II) is highly psychotropic in mice, rats and pigeons. The (+)-(3S,4S) enantiomer (III) was found to be psychotropically inactive at doses up to several thousand times those of the ED50 of (II).

Animals↗

Potential metabolic mutagens of caffeine and various methylxanthines.

Xanthine N-carbinols, potential metabolites of caffeine and other methylxanthines, have been synthesized, characterized, and derivatized. Such intermediates, the initial metabolites arising from the cytochrome P-450 oxidation of the nitrogen-bound methyl groups, may be viewed as biological N-carbinols capable of alkylating proteins and nucleic acids. Evaluation of these compounds against Salmonella typhimurium, strain TA100, has demonstrated that, in contrast to caffeine, 7-hydroxymethyltheophylline and the 3,7-bis(hydroxymethyl)-1-methylxanthine mixture did exhibit cytotoxicity. There was no evidence of mutagenesis and it is possible that the Ames assay system is not applicable to N-carbinols.

Animals↗

Method for testing the sterility of total nutrient admixtures.

A test for determining the sterility of a total nutrient admixture (TNA) containing equal quantities of 10% fat emulsion (Liposyn II), 8.5% amino acids injection, and 50% dextrose injection using the USP membrane filtration procedure was developed and evaluated. Membrane filter selection was determined by analysis of flow rates, membrane fluid compatibility, bubble point stability, and rinse fluid requirements. Microbial challenges employing five organisms (Bacillus subtilis, Escherichia coli, Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa) and both soybean casein digest and fluid thioglycollate media were used to confirm the ability of the test to detect low-level microbial contamination. A polyvinylidene fluoride membrane was determined to be the most appropriate of the membrane types studied because of its superior flow rate and membrane-fluid compatibility. Bubble point testing revealed no detrimental effects on the membrane. The potential problem of haziness caused by retention of the TNA by the membrane with subsequent release in the culture media (which could result in false-positive growth determinations) was diminished by using a sterile 0.1% peptone solution rinse and careful observation techniques. Performance of the sterility test by six hospital pharmacists required an average of 14.2 minutes. Sterility testing of alternate TNAs compounded with Intralipid and Nutralipid was not feasible because of prolonged filtration times. The basic USP membrane filtration procedure for large-volume injections can be used by hospital pharmacists for testing the sterility of TNAs. When fat emulsions are used in compounding, sterility-testing procedures specific to the emulsion product used should be developed and evaluated.

Culture Media↗

Stereochemical requirements for cannabimimetic activity.

The SAR of cannabimimetic activity in the cannabinoid series are reviewed with emphasis on the stereochemical requirements. Some new results are presented. The most important are that a, in humans, (-)-(1S)-delta-3-THC is much more active than (+)-(1R)-delta-3-THC; and b, with the 7-OH-delta-6-THC DMH enantiomers (32) and (33), the activity in several animal species resides completely in the (-)-(3R, 4R) enantiomer (32), the difference between the two enantiomers being up to several thousand times. The (3R,4R)-enantiomer (32) is much more active than delta-1- or delta-6-THC in animal tests, the exact level of activity depending on the test employed. The cannabimimetically inactive (+)-(3S,4S) enantiomer (33) was shown to be a potent analgetic in several animal tests. Thus, a complete dissociation between the cannabimimetic and the analgetic effects in a cannabinoid has been achieved, apparently for the first time.

Analgesics↗

Structure-anticonvulsant activity relationships of cannabidiol analogs.

Cannabidiol (CBD) exhibits anticonvulsant activity in experimental animals and in man. As part of a structure-activity study, analogs were prepared wherein the terpene unit, the aryl unit, and/or the side chain were modified. Thus, several pinenyl and carenyl derivatives, aryl ethers and acetates, and a variety of 1",1"-dialkylhexyl and 1",1"-dialkylheptyl analogs were synthesized. The compounds were evaluated for anti-convulsant activity in seizure susceptible (AGS) rats and for neurotoxicity in the rat rotorod (ROT) test. Comparisons of stereoisomers of CBD and several analogs revealed a general lack of stereoselectivity for anticonvulsant and other CNS properties of this class of compounds.

Animals↗

Cannabimimetic activity (delta 1-THC cue) of cannabidiol monomethyl ether and two stereoisomeric hexahydrocannabinols in rats and pigeons.

Animals (rats and pigeons) trained to discriminate between the presence and absence of the effects of delta 1-tetrahydrocannabinol (delta 1-THC; 3 and 0.56 mg/kg, respectively) were tested for generalization with graded doses of delta 1-THC as well as with two 7-hydroxyhexahydrocannabinol epimers which differ in the stereochemistry at the C-1 position only, and a cannabidiol (CBD)-like compound, cannabidiol monomethyl ether (CBDM). delta 1-THC produced dose/time related effects in both rats and pigeons. Both 7-hydroxyhexahydrocannabinols generalized with delta 1-THC in both species. Greater cannabimimetic activity was observed when the substituent at the C-1 position was equatorial (as in compound NL-105) than when the substituent was axial (compound NL-106) (for chemical structures see Fig. 1, below). Thus in the absence of other substituents the planarity at the C-1 position determines cannabimimetic activity. CBDM induced only vehicle appropriate responding at the doses of 3 and 10 mg/kg in both species; 30% delta 1-THC appropriate responding occurred with 17.5 mg/kg (only tested in pigeons), a dose which also appeared to excert rate depressant effects. Thus, like CBD, CBDM has a low degree of cannabimimetic activity.

Animals↗

Specific impairment of ADP-induced platelet aggregation by cannabinoids.

The structure-activity relationship of the inhibition of ADP-induced platelet aggregation by cannabinoids was studied. A marked specificity was revealed: derivatives in which the two asymmetric centers have a configuration opposite to that of the natural cannabinoids and have a dimethylheptyl (DMH) side-chain were most inhibitory. It is concluded that the mode of inhibition includes a specific interaction of the cannabinoids with some membrane proteins, possibly including the receptor for ADP.

Adenosine Diphosphate↗

Conformation, dynamics, and structural transitions of the TATA box region of self-complementary d[(C-G)n-T-A-T-A-(C-G)n] duplexes in solution.

Structural and kinetic features of the TATA box located in the center of the alternating self-complementary d(C-G-C-G-T-A-T-A-C-G-C-G) duplex (TATA 12-mer) and d(C-G-C-G-C-G-T-A-T-A-C-G-C-G-C-G) duplex (TATA 16-mer) have been probed by high-resolution proton and phosphorus NMR spectroscopy in aqueous solution. The imino exchangeable Watson-Crick protons and the nonexchangeable base protons in the TATA box of the TATA 12-mer and TATA 16-mer duplexes have been assigned from intra and inter base pair nuclear Overhauser effect (NOE) measurements. Imino proton line-width and hydrogen exchange saturation recovery measurements demonstrate that the dA X dT base pairs in the TATA box located in the center of the TATA 12-mer and TATA 16-mer duplexes are kinetically more labile than flanking dG X dC base pairs. The proton and phosphorus NMR parameters of the TATA 12-mer monitor a cooperative premelting transition in the TATA box prior to the onset of the melting transition to unstacked strands. Phosphorus NMR studies have been unable to detect any indication of a right-handed B DNA to a left-handed Z DNA transition for the TATA 12-mer duplex in saturated NaCl solution. By contrast, we do detect the onset of the B to Z transition for the TATA 16-mer in saturated NaCl solution. Proton and phosphorus NMR studies demonstrate formation of a loop conformation with chain reversal at the TATA segment for the TATA 12-mer and TATA 16-mer duplexes on lowering the DNA and counterion concentration. The imino protons (10-11 ppm) and phosphorus resonances (3.5-4.0 ppm; 4.5-5.0 ppm) of the loop segment fall in spectral windows well resolved from the corresponding markers in fully paired segments so tha it should be possible to identify loops in longer DNA helixes. The equilibrium between the loop and fully paired duplex conformations of the TATA 12-mer and TATA 16-mer is shifted toward the latter on addition of moderate salt.

Base Sequence↗

Activity of novel aminocannabinoids in baboons.

The axial and equatorial isomers of 7-(methylamino)hexahydrocannabinol (1 and 2) and 7-(dimethylamino)hexahydrocannabinol (3 and 4) were prepared by reductive amination of the corresponding cannabinoid aldehydes. The amines caused some tranquility in baboons but did not evoke the typical cannabimimetic syndrome caused by psychoactive cannabinoids. However the axial amines (1 and 3) but not the equatorial ones (2 and 4) caused bouts of scratching and yawning. The latter is a rare pharmacological effect hitherto not observed with other cannabinoids.

Animals↗

Anticonvulsant effects of the (-) and (+)isomers of cannabidiol and their dimethylheptyl homologs.

The anticonvulsant actions of the (-) and (+)isomers of cannabidiol and dimethylheptyl-cannabidiol were studied with the maximal electroconvulsive shock model in mice. The ratio of the times for hindlimb extension and fore limb flexion was recorded as an anticonvulsant index. All the cannabinoids were anticonvulsant. They also potentiated pentobarbitone sleeping time. The (+)isomer was more active than the (-)isomer. Possible mechanisms of actions on receptors or membranes are discussed.

Animals↗

Reduction of hippocampal acetylcholine turnover in rats treated with (-)-delta 8-tetrahydrocannabinol and its 1',2'-dimethyl-heptyl homolog.

The effects of (-)-delta 8-tetrahydrocannabinol (THC), (+)-delta 8-THC, and the dimethyl-heptyl (DMH) homolog of (-)-delta 8-THC (delta 8-THC-DMH) have been compared with the action of (-)-delta 9-THC on the turnover rate of acetylcholine in various brain areas. The data demonstrate that (-)-delta 8-THC-DMH, (-)-delta 9-THC and (-)- delta 8-THC all specifically reduce ther turnover rate of acetylcholine in the hippocampus in a dose-dependent manner ((-)-delta 8-THC-DMH > (-)-delta 9-THC > (-)-delta 8-THC) without altering the acetylcholine or choline content (except for high doses of (-)-delta 8-THC-DMH). The (+)-isomer of delta 8-THC fails to change any cholinergic parameter. The selectivity of action suggests that the tetrahydrocannabinoids may activate specific transmitter receptors which indirectly modulate the activity of the cholinergic neurons in the septal-hippocampal pathway.

Acetylcholine↗

Stereochemical requirements for cannabinoid activity.

Several pairs of cannabinoid isomers were synthesized and tested for psychotropic activity in rhesus monkeys. Two regularities were observed: (a) In the absence of the other substituents, the equatorial stereochemistry of the substituent at C-1 determines activity. (b) Two groups of THC-type cannabinoids which differ only in that the chemical groupings in one of them at C-1, C-2 are situated at C-1, C-6 in the other (but retain their stereochemistry) have almost equivalent psychotropic activity.

Animals↗

Chronic administration of cannabidiol to healthy volunteers and epileptic patients.

In phase 1 of the study, 3 mg/kg daily of cannabidiol (CBD) was given for 30 days to 8 health human volunteers. Another 8 volunteers received the same number of identical capsules containing glucose as placebo in a double-blind setting. Neurological and physical examinations, blood and urine analysis, ECG and EEG were performed at weekly intervals. In phase 2 of the study, 15 patients suffering from secondary generalized epilepsy with temporal focus were randomly divided into two groups. Each patient received, in a double-blind procedure, 200-300 mg daily of CBD or placebo. The drugs were administered for along as 4 1/2 months. Clinical and laboratory examinations, EEG and ECG were performed at 15- or 30-day intervals. Throughout the experiment the patients continued to take the antiepileptic drugs prescribed before the experiment, although these drugs no longer controlled the signs of the disease. All patients and volunteers tolerated CBD very well and no signs of toxicity or serious side effects were detected on examination. 4 of the 8 CBD subjects remained almost free of convulsive crises throughout the experiment and 3 other patients demonstrated partial improvement in their clinical condition. CBD was ineffective in 1 patient. The clinical condition of 7 placebo patients remained unchanged whereas the condition of 1 patient clearly improved. The potential use of CBD as an antiepileptic drug and its possible potentiating effect on other antiepileptic drugs are discussed.

Adult↗