Affinity profiles of BTM-1086 and BTM-1041 at muscarinic receptor subtypes and at H1- and alpha 1-receptors

The affinities of the (+) and (-) enantiomers of the antimuscarinic benzothiazepinone derivative, cis-2,3-dihydro-3-(4-methyl-1-piperazinylmethyl)-2-phenyl-1,5-benzoth iazepin-4 (5H)-one (BTM-1041 and BTM-1086), for muscarinic receptor subtypes, histamine H1-receptors and alpha 1-adrenoceptors were determined in vitro using isolated organs: field-stimulated rabbit vas deferens (M1-receptors), guinea-pig left atrium (M2-receptors), guinea-pig ileum (M3- and histamine H1-receptors) and rat vas deferens (alpha 1-adrenoceptors). We also assessed the binding profile of BTM-1041 and BTM-1086 at muscarinic receptor subtypes in guinea-pig cortex (M1), heart (M2) and salivary glands (M3) as well as at alpha 1-adrenoceptors in rat cerebral cortex. Functional and binding experiments showed that the (-) enantiomer (BTM-1086) had a high affinity (pA2 = 7.98-8.81; pKi = 8.31-9.15) for the three muscarinic receptor subtypes, whereas the (+) enantiomer (BTM-1041) showed a low antimuscarinic potency (pA2 = 4.87-5.31; pKi = 4.85-5.55). This results in an extremely high stereoselectivity for these optical isomers [-)/(+) ratios = 1023 to 6918). The affinity of the (-) enantiomer BTM-1086 was lower for both histamine H1- and alpha 1-receptors than for muscarinic receptors, whereas the reverse was true for the (+) enantiomer, BTM-1041. Thus, the stereochemical demands for the two optical isomers were most stringent at muscarinic receptors but were inverse and less pronounced at histamine H1- and alpha 1-receptors (stereoselectivity ratios = 0.16-0.22).     

Choreoacanthocytosis in a Chinese patient--a case report

A 50-year old Chinese woman with the rare neurological disorder of Choreoacanthocytosis is described. Her illness is characterised by seizures, buccolingual dyskinesia, choreiform movements, arreflexia and mild sensorimotor polyneuropathy. Acanthocytes were present in her peripheral blood in large numbers but the serum lipid profile was normal. Her features are consistent with those so far described in Caucasian and Japanese patients. The disease differs from Huntington's chorea in that there are acanthocytes, peripheral neuropathy, and metal function remains relatively intact.     

Schistosomiasis caused by Schistosoma mansoni in Baringo District, Kenya: case report

Schistosomiasis caused by Schistosoma mansoni has not been reported in Baringo District of Rift Valley Province. The intermediate host (Biomphalaria species) though has been reported to occur along the shores of the lakes in this region. Three children from Baringo District were diagnosed to have schistosomiasis caused by S. mansoni by finding ova in their stools. They gave no history of visiting an endemic area. There are many dams being built for land reclamation, creating favourable conditions for the spread of the disease, in presence of the intermediate and definitive host. Studies on the current status of the disease and malacology should be undertaken in order to control the spread of the disease at an early stage.     

Melatonin and Sperm Motility/Melatonin und Spermatozoenmotilität

Several substances can interfere with microtubular function eg. colchicine. Melatonin, a hormone secreted by the pineal gland has similar effects as colchicine on microtubules. In this study melatonin levels were determined in both plasma and seminal plasma of patients with good or impaired motility and forward progression. There was no statistically significant difference between the mean plasma and seminal plasma values of patients with good or impaired motility and forward progression. There was no correlation between seminal plasma melatonin and impaired motility or any other semen parameter. There was also no correlation between plasma and seminal plasma concentrations of melatonin. High seminal plasma melatonin concentrations were not necessarily associated with impaired sperm motility. From these it is concluded that seminal plasma melatonin plays no important role in sperm motility.     

Motor nerve conduction velocity distributions in man: results of a new computer-based collision technique

A new computer-based collision technique for direct measurement of the human motor nerve conduction velocity distribution is described. In contrast to previous collision techniques, the test muscle response is progressively cancelled to a null using an arrangement of proximal and distal stimuli which eliminates distortion of the test response caused by transient changes in nerve and muscle fibre conduction. The increased sensitivity of this new technique permits accurate measurement of the slowest 1% of alpha motor nerve fibres. We have used our modified collision technique to determine motor nerve conduction velocity distributions for the median nerve in 20 normal subjects aged between 19 and 59 (mean 35) years. 150% maximal stimulus intensities were used, with a controlled limb temperature of 35 degrees C. Group mean velocities (+/- S.D.) for the fastest (95%), mean (50%) and slowest (5% and 1%) motor fibres were 59.1 +/- 3.0, 56.9 +/- 2.9, 52.7 +/- 3.1 and 51.2 +/- 3.7 m/sec respectively. Data are also presented for the ulnar and peroneal nerves.     

Ameloblastoma with multiple delayed recurrences: a case report

The ameloblastoma is a tumor arising predominantly in the mandible from odontogenic epithelium, and is locally invasive. It is rarely malignant; but even when benign, it causes gross local destruction and expansion of tissue. Growth is persistent, and recurrence may occur more than a decade after presumed total resection. Surgical resection should include a reasonable margin of healthy tissue whenever possible. Late patient presentation due to a paucity of symptoms, and insiduous tumor growth patterns render complete removal of the ameloblastoma difficult. Follow-up examinations should span a prolonged period, exceeding 10-15 years.