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Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand gated ion channels, which are found at the neuromuscular junction and in the central and peripheral nervous systems. The channels can be assembled from fourteen known subunits. The exact combination and function of all the channels are still not determined but in the CNS certain combinations have been identified which appear to modulate the release of specific neurotransmitters. Non-specific nAChR agonists like nicotine and epibatidine, have been shown to have interesting pharmacology but their clinical value is limited by their undesirable side effects. Selective ligands for different receptor subtypes have been reported and these compounds are probably the best tools for determining the function of the subtypes. The expectation is that some receptor subtype selective nAChR ligands will be clinically useful for the treatment of a broad range of CNS disorders. The development of stable cell lines functionally expressing specific combinations of subunits has greatly improved our understanding of ligand specificity. There have also been advances in the modelling of the ligand binding site, thanks to the discovery of a homologous snail ACh binding protein the X-ray structure of which was determined in 2001. These techniques should lead to rapid advances in the development of truly subtype selective ligands. In this review we describe recent progress in the area and describe the first 1000 fold selective low molecular weight ligands from the AstraZeneca group. We also comment on the first subtype specific channel modulators.

A simple method for the determination of human corneal epithelial permeability to fluorescein is presented. The method consists of applying a 1% sodium fluorescein solution to the cornea for 3 minutes by means of an eye bath, rinsing the eye, and measuring corneal fluorescence by fluorophotometry. The permeability value is calculated from the corneal fluorescein concentration immediately after the bathing period.Mean permeability value determined in 86 eyes of 46 volunteers aged 15 to 67 years (mean 30.9 years) was 0.038 nm/s ± 0.017 SD. No significant correlation with age was found (corr. coeff. = 0.17, P = 0.28).The reproducibility was within 10%.

Uncomplicated urogenital and concomitant oropharyngeal gonorrhea in 424 male and female patients was treated in a randomized comparative study with 0.5 g of cefodizime (89 men and 54 women), 1 g of cefodizime (87 men and 52 women), or 1 g of cefotaxime (86 men and 56 women). The cure rates were 100% for men and women in the group given 0.5 g of cefodizime, 100% for men and women in the group given 1 g of cefodizime, and 99% for men and 100% for women in the group given 1 g of cefotaxime. The MICs of cefodizime and cefotaxime for the isolate of Neisseria gonorrhoeae ranged from 0.004 to 0.06 micrograms/ml. Chlamydia trachomatis was isolated before treatment in 15% and after treatment in 13% of all patients. Side effects, such as nausea, diarrhea, abdominal pain, genital candidiasis, and pain at the site of injection, developed in 4% of the patients given cefodizime. Side effects, such as vertigo, genital candidiasis, fatigability, and diarrhea, developed in 4% of the patients treated with cefotaxime. In both groups of patients, the side effects were mild and transient. Cefodizime and cefotaxime are safe and effective agents in the treatment of uncomplicated urogenital gonorrhea.

Two useful methods for determination of the decay curve of non-protein bound fluorescein (NPBF) in plasma up to 1 hour after intravenous fluorescein injection are described and evaluated. The course of NPBF is approximated in method 1 by a sum of two exponential decay functions and in method 2 by a power of time function. The parameters in these functions are calculated with the use of concentration values measured in two blood samples taken at about 5 min. and 60 min. after injection. Calculations in method 1 include the amount of fluorescein injected.

The effect of the local anaesthetics oxybuprocaine (OBu) and tetracaine (Tetra) and the preservatives chlorhexidine (CH) and benzalkonium chloride (BAK) on corneal epithelial permeability was studied by fluorophotometry in normal human eyes. Five instillations of one drop ophthalmic solution of the compounds were administered to one eye at 2-minute intervals; a control solution was instilled into the fellow eye.The increase in corneal epithelial permeability, expressed as the permeability ratio between the treated and control eye, was not significant after instillation of the anaesthetics. The preservatives and the combination OBu+CH increased corneal epithelial permeability significantly (P < 0.05). OBu+BAK and Tetra+BAK increased permeability to a far greater extent (P < 0.005).

The permeability of the blood retinal barrier (PBRB) and the diffusion coefficient into the anterior chamber (kd) in 20 insulin dependent (ID) and in 11 non-insulin dependent (NID) diabetics with various degrees of retinopathy were determined by fluorophotometry with a 25% accuracy. The difference of PBRB and the kd values between the NID and the ID patients was not significant (p > 0.05 and p > 0.22).

THE ability of lung tissue from various species to synthesise and release parent prostaglandins (PGs) has been well established1,2and metabolic conversions of PGs occur rapidly after very efficient uptake from the circulation3,4. Using an isolated perfusion system to allow uptake of the PG precursor, arachidonic acid (1-14C labelled), the sensitised guinea pig lungs released a number of radiolabelled substances following challenge with specific antigen5. Our attempts to characterise these substances and prepare sufficient material for biological testing have revealed at least two compounds which have not been previously described and others not previously seen in this release system.

The condition of the corneal epithelium of 57 non-, 18 soft-, 29 gas-permeable-and 26 hard contact lens-wearing eyes was investigated by fluorophotometric determination of the corneal epithelial permeability.The mean permeability values for non-, soft-, gas-permeable-and hard contact lens-wearing eyes were 0.040 nm/s + 0.017 SD, 0.02U nm/s + 0.009 SD, 0.028 nm/s + 0.017 SD and 0.044 nm/s + 0.020 SD, respectively. The mean permeability values for soft and gas-permeable contact lens-wearing eyes were significantly lower than that for non contact lens-wearing eyes (-40%, p < 0.0001 and-30%, p < 0.005); no significant difference was found between the mean values for hard and non contact lens-wearing eyes (p=0.38).

From 1982 to 1985 the 19S IgM-Fluorescent Treponemal Antibody Absorption (19S-IgM-FTA-ABS) test gave a positive result in 19 children. These 19 children plus one dizygotic twin sister were evaluated. Seventeen children were diagnosed as having congenital syphilis and treated. Clinical evidence was seen in 10 children, CSF abnormalities in seven, radiological abnormalities in eight. Of the 17 children treated, only one did not meet the Center for Disease Control (CDC) criteria of a compatible case of congenital syphilis. Of the children not diagnosed as having congenital syphilis, one child was considered to be a compatible case of congenital syphilis according to the CDC-criteria. The CDC-criteria may be a valuable aid in diagnosing congenital syphilis. Guidelines for adequate therapy are given. [ABSTRACT FROM PUBLISHER]

The safety and efficacy of intralesionally administered interferon alfa-2b were assessed in 11 patients suffering from condylomata acuminata for four to 10 months for whom application of podophyllum resin had proved unsuccessful. Three warts from each patient were injected with 10(6) IU interferon alfa-2b three times a week for three weeks. Treatment was followed by a 13 week observation period. Interferon alfa-2b treatment resulted in a highly significant (p less than 0.0001) reduction in the mean size of the treated warts, which decreased from an initial size of 29 mm2 to 2-3 mm2 by week 16. In six out of the 10 patients completing the trial, both the test condylomata and adjacent control warts cleared completely; a recurrence was observed in one of these six patients. Influenza like symptoms (headache and myalgia) were the most common side effects reported, though they were mild in nature and not disabling. These results corroborate those of previous trials with interferon preparations and indicate that its antiviral activity makes it a possible treatment for this sexually transmitted disorder. [ABSTRACT FROM PUBLISHER]

During 1982-5 the 19S (IgM) fluorescent treponemal antibody absorption (19S (IgM) FTA-ABS) test gave positive results in 19 children. The parental histories were analysed. As five of the children were adopted, 14 pregnancies were evaluated. Mothers of foreign origin and extramarital pregnancies were found to be over-represented. Of 13 women who attended for pregnancy checkup, three were not serologically screened for syphilis. In four the infection had developed late in the course of pregnancy. In at least four treatment had not been given or had been inadequate or too late. At least two had positive 19S (IgM) FTA-ABS test results that did not indicate congenital syphilis. The possibility of false positive 19S (IgM) FTA-ABS test results is pointed out. As the male sexual partners of four of the 14 mothers had presented elsewhere with early syphilis at the time of their partner's pregnancy, adequate contact tracing appears to be important to prevent congenital syphilis in future. [ABSTRACT FROM PUBLISHER]