Renal cell cancer and sorafenib: skin toxicity and treatment outcome

We describe the case of a young man with refractory renal cell carcinoma who achieved an objective response in a metastatic lesion after biotherapy with the multikinase inhibitor sorafenib and also developed a severe skin reaction. The patient had been previously treated with various combinations of immunochemotherapy without any clinical benefit. We performed a brief review of the literature where similar cases were documented with the use of various anti-EGFR agents. The hypothesis of the correlation of skin toxicity with disease response is not new, but in the absence of any strong evidence remains controversial.     

Loss of the endothelial glycocalyx links albuminuria and vascular dysfunction

Patients with albuminuria and CKD frequently have vascular dysfunction but the underlying mechanisms remain unclear. Because the endothelial surface layer, a meshwork of surface-bound and loosely adherent glycosaminoglycans and proteoglycans, modulates vascular function, its loss could contribute to both renal and systemic vascular dysfunction in proteinuric CKD. Using Munich-Wistar-Fromter (MWF) rats as a model of spontaneous albuminuric CKD, multiphoton fluorescence imaging and single-vessel physiology measurements revealed that old MWF rats exhibited widespread loss of the endothelial surface layer in parallel with defects in microvascular permeability to both water and albumin, in both continuous mesenteric microvessels and fenestrated glomerular microvessels. In contrast to young MWF rats, enzymatic disruption of the endothelial surface layer in old MWF rats resulted in neither additional loss of the layer nor additional changes in permeability. Intravenous injection of wheat germ agglutinin lectin and its adsorption onto the endothelial surface layer significantly improved glomerular albumin permeability. Taken together, these results suggest that widespread loss of the endothelial surface layer links albuminuric kidney disease with systemic vascular dysfunction, providing a potential therapeutic target for proteinuric kidney disease.     

Synthesis and Pharmacological Activity of 1,6-Bisaryl-2,5-bis(aminomethyl)-1,6-hexanedione Dihydrochlorides. Synthesis of 1,8-bisaryl-2,7-bis(aminomethyl)-1,8-octanedione Dihydrochlorides

Pharmaceutical Chemistry Journal -     

Synthesis of 2-(4-substituted phenyl)-3-[4-substituted piperazino(piperidino)]propan-1-ol dihydrochlorides and their effects on adenosine deaminase activity

Aminomethylation of 4-substituted acetophenones yielded a series of β-amino-4-substituted propiophenones. Reduction of these with lithium alumohydride in dry ether produced 1-(4-substituted phenyl)-3-[4-substituted piperazino(piperidino)]propan-1-ols, which were then converted to the corresponding dihydrochlorides. The abilities of these compounds to inhibit adenosine deaminase, a key enzyme in purine metabolism in living organisms, were studied. Some of the compounds had quite marked inhibitory effects on the enzyme. The abilities of the compounds synthesized here to inhibit adenosine deaminase were found to depend on their structure. It is of note that virtually all the compounds inhibited the high molecular weight form of the enzyme to a significantly lesser extent than the low molecular weight form.     

Synthesis and biological properties of 2-(4-chlorophenyl)-3-morpholin-4-yl-(4-alkoxyphenyl)alkanol hydrochlorides

New 2-(4-chlorophenyl)-3-morpholin-4-yl-1-(4-alkoxyphenyl)propan-1-ones were synthesized via aminomethylation of 2-(4-chlorophenyl)-1-(4-alkoxyphenyl)ethanones. Reduction of the former by lithium aluminum hydride produced 2-(4-chlorophenyl)-3-morpholin-4-yl-1-(4-alkoxyphenyl)propan-1-ols. Reaction of them with Grignard reagents gave 2-(4-chlorophenyl)-1-morpholin-4-yl-3-(4-alkoxyphenyl)alkan-3-ols. The synthesized compounds exhibited pronounced anticonvulsive and some peripheral n-cholinolytic activities while showing no antibacterial activity.     

A late recognition of tapia syndrome

Tapia syndrome is characterized by concurrent paralysis of the recurrent laryngeal and hypoglossal nerves. The mechanism is associated with airway manipulation in 70% of patients and is attributed to compression or stretching of these nerves. Diagnosis is based on recognition of the concurrent paralyses and investigations to exclude central or vascular causes. Treatment is supportive, with emphasis on empiric corticosteroids and dysphagia therapy. Recovery is excellent in 30% of patients, incomplete in 39% of patients, and none in over 26% of patients. A case of a 48‐year‐old woman is described, who was diagnosed with Tapia syndrome 3 years after the suspected injury. Laryngoscope, 123:2423–2427, 2013