Optimization of a previously disclosed sorbitol dehydrogenase inhibitor (SDI, II) for potency and duration of action was achieved by replacing the metabolically labile N,N‐dimethylsulfamoyl group with a variety of heterocycles. Specifically, this effort led to a series of novel, in vitro potent SDIs with longer serum half‐lives and acceptable in vivo activity in acutely diabetic rats (e.g., 62, 67, and 69). However, the desired in vivo potency in chronically diabetic rats, ED90 less than or equal to 5 mg/kg/day, was achieved only through further modification of the piperazine linker. Several members of this family, including 86, showed better than the targeted potency with ED90 values of 1‐2 mg/kg/day. Compound 86 was further profiled and found to be a selective inhibitor of sorbitol dehydrogenase, with excellent pharmacodynamic/pharmacokinetic properties, demonstrating normalization of sciatic nerve fructose in a chronically diabetic rat model for approximately 17 h, when administered orally at a single dose of 2 mg/kg/day.
We report a pathologically documented case of infarction of the dominant thalamus with extensive involvement of the ventral lateral, ventral posterolateral, and lateral posterior nuclei and some involvement of the pulvinar. This patient exhibited linguistic impairment with features fairly typical for thalamic lesions. He also demonstrated a severe ideomotor apraxia. The preservation of repetition, syntax, and implicit memory despite severe naming deficits in patients with thalamic lesions suggests the possibility that thalamic involvement in cognitive function involves processes underlying declarative as opposed to nondeclarative (eg, implicit or procedural) memory. The occurrence of apraxia with thalamic lesions may be consistent with this hypothesis if it is accepted that only actual tool use approaches a pure skill that involves only nondeclarative memory, while other aspects of praxis implicate declarative memories.
MethodsCase report The patient was a 66-year-old male with a long history of hypertension, who, while working in the sun, became weak and collapsed. At the time of hospital admission examination showed confusion, a mixed transcortical aphasia, right hemiparesis and right hemisensory deficit. Ten days after admission neurological examination revealed a mild right facial weakness, a right hemiparesis with arm weaker than leg and distal muscles weaker than proximal muscles, and a right hemisensory deficit for graphaesthesia and stereognosis, vibration, pin and touch sensation. Grasp, suck, and root responses were present. Reflexes were enhanced and the Babinski sign was present bilaterally. Cerebellar examination was within normal limits. CT revealed a radiolucent area confined to the left thalamus. Three days after electrophysiological recordings were made the patient suffered cardiorespiratory arrest from which he could not be resuscitated.Postmortem examination of the brain revealed atherosclerosis involving the major cerebral arteries with marked involvement of the left posterior cerebral artery just distal to the junction of the left posterior communicating artery. A thrombus was found in this region which extended for approximately 1-0 cm. This thrombus apparently occluded perforating vessels which serve portions of the thalamus.
Antibiotic usage has rendered neurosyphilis uncommon, and cerebral gummas are rare. Reduced awareness of cerebral gummas and abolition of serologic screening can delay diagnosis of this treatable disease. Diagnostic confusion between syphilitic and nonsyphilitic cerebral mass lesions can be increased by apparent resolution of a gumma during steroid therapy. Such an occurrence in a young woman emphasizes the need for serologic testing for syphilis in diagnosing cerebral mass lesions. A trial of conservative therapy using penicillin (with or without prednisone) should be considered for patients with intracerebral mass lesions and positive serologic findings.
Since the techniques of column, paper, thin layer, and gas chromatography are playing a rapidly increasing role in horticultural laboratories and in the interests of horticulturists, two papers on chromatography technique are presented in this issue. W. E. Ballinger and Eleanor P. Maness of North Carolina State University offer an improvement in paper chromatography which has enabled them to materially increase laboratory productivity in the separation of anthocyanins from blueberries. M. Allen Stevens of Campbell Research Institute briefly, but concisely, surveys the principles of gas chromatography and illustrates several horticultural research potentials with this new medium.
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