Discovery and development of direct thrombin inhibitors the binding site for the globular amino-terminal domain and exosite 1 is the binding site for the acidic carboxy-terminal domain of hirudin. Native hirudin, a 65-amino-acid polypeptide, is produced in the parapharyngeal glands of medicinal leeches. Hirudins today are produced by recombinant biotechnology using yeast. These recombinant hirudins lack a sulfate group at Tyr-63 and are therefore called desulfatohirudins. They have a 10-fold lower binding affinity to thrombin compared to native hirudin, but remain a highly specific inhibitor of thrombin and have an inhibition constant for thrombin in the picomolar range. Renal clearance and degradation account for the most part
Salivary duct stricture Salivary duct stricture Salivary duct stricture (also termed salivary duct stenosis) is narrowing of the duct of a major salivary gland. Strictures are the second most common cause of chronic obstructive sialadenitis, after salivary stones. In line with this, strictures may give rise to the "meal time syndrome", where there is pain and swelling of the involved salivary gland upon salivary stimulation with the sight, smell and taste of food. In other cases, there is irregular and intermittent pain and swelling of the gland which is not related to meal times. Typically the swelling is present upon waking or occurs