Cannabinoids are the constituents of the marijuana plant (cannabis sativa) of which the major active ingredient is delta-9-tetrahydrocannabinol (delta 9-THC). Rapid progress has been achieved in marijuana research in the last five years than in the thousands of years that marijuana has been used in human history. For many decades therefore, research on the molecular and neurobiological bases of the physiological and neurobehavioral effects of marijuana was hampered by the lack of specific research tools and technology. The situation has started to change with the availability of molecular probes and other recombinant molecules that have led to major advances. Recent advances include the cloning of the cDNA sequences encoding the rat, human and the mouse peripheral and CNS cannabinoid receptors. In addition a putative ligand, anandamide, thought to represent the endogenous cannabis-like substance that binds the cannabinoid receptors, has been isolated from the brain. This achievement has opened a whole new neurochemical system particularly as the physiological and pharmacological properties of anandamide indicate a possible neuromodulatory or neurotransmitter role. The recent demonstration of a potent and selective antagonist for CBl receptors may become an important and powerful investigative tool. Future progress on the neurobiology of cannabinoid research may include data on the use of antisense strategies and gene targeting approach to further understand the mechanism(s) of action of cannabinoids which has been slow to emerge. We conclude that these are exciting times for cannabis research which has given us anandamide--a substance of inner bliss.

Animals↗

PubMedDate not supplied

Leishmania mexicana amazonensis: differential display analysis and cloning of mRNAs from attenuated and infective forms.

The virulence of Leishmania mexicana is determined by the concerted action of several parasite molecules. These cells lose their infectivity to host macrophages after prolonged cultivation in axenic growth media. Both virulent and attenuated variants of the parasite cells were cloned. The differential display reverse transcription-polymerase chain reaction technique was employed to understand whether this natural attenuation of the parasite cells is accompanied by differential expression of selected genes in those cells. Twelve different dinucleotide-anchored oligo(dT) antisense primers were used to make cDNAs from poly(A)+ mRNAs isolated from a clonal population of virulent and avirulent cells following a protocol optimized for Leishmania mRNAs. Those cDNAs were subjected to amplifications using each of the three different arbitrary decanucleotide primers and the corresponding anchored oligo(dT) primer. This procedure revealed four virulent-specific cDNA probes and one avirulent-specific cDNA probe. Differential expressions of these genes were confirmed by northern hybridization using the cloned cDNA probes. These results indicate that differential expression of genes may be the key in determining the molecular basis of leishmanial virulence.

Animals↗

PubMedDate not supplied

A specific and sensitive radioimmunoassay for human choriogonadotropin.

A specific and sensitive radioimmunoassay for human choriogonadotropin (hCG) has been developed using rabbit antiserum to chemical analogs of beta subunit of human chorionic gonadotropin prepared by controlled reduction and S-alkylation of its disulfide linkages. The assay was highly specific for hCG as the binding of [125I]-hCG to the antibody was not affected by standard human lutropin, by human male serum, postpartum serum from women, serum from post-menopausal women and human menopausal gonadotropin (Pergonal). The assay was highly sensitive, the minimal detection limit in terms of highly purified hCG (L-129, 12500 IU/mg) being 1 ng/ml or 0.2 ng/tube (or 12 mlU/ml in terms of WHO 2nd international reference preparation of hCG). Using this assay we were unable to detect any immunoreactive hCG in human tissues like lung, liver and colon. The high specificity, sensitivity, accuracy and reproducibility of the assay make this a highly desirable radioimmunoassay for human choriogonadotropin.

Chorionic Gonadotropin↗

PubMedDate not supplied

Compelled weightbearing in persons with hemiparesis following stroke: the effect of a lift insert and goal-directed balance exercise.

The hypotheses have been tested that 1) symmetry of weightbearing in persons who have sustained a stroke could be improved by the addition of a lift to the shoe on the non-paretic lower limb and 2) compelled weightbearing resulting from the addition of a lift in conjunction with targeted exercise helps to overcome the learned disuse of the paretic limb. Weightbearing on the paretic side was measured in eight persons with hemiparesis during quiet standing and in conditions of compelled weight shift. Compelled weight shifts were applied with special lifts to the shoe on the non-paretic limb of the subjects. An increase in symmetrical weightbearing was recorded in conditions of compelled weight shifts: 10-mm lift provided the best symmetry of bipedal standing. We suggest that improved symmetry of bipedal standing obtained with the lift of the non-paretic limb would help in overcoming the learned disuse of the affected limb. Pre- and post-test results of a person with hemiparesis who was wearing a shoe lift on the non-paretic limb during a 6-week physical therapy program showed statistically significant improvement of walking speed, stride length, and weightbearing. Such findings support the idea of using compelled weightbearing via lifting and targeted exercise during treatment.

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