Biological activity of fluorinated 3,4-dihydroisoquinolines

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 26, No. 1, pp. 44–45, January, 1992.     

Correction of hypercholesterolemia and dyslipoproteinemia by plasmapheresis in patients with stenocardia resistant to drug therapy

Plasmapheresis was used to correct blood lipid composition in patients with angina at rest and angina of effort (functional classes 3-4). In addition to a drop in total cholesterol and triglycerides, cholesterol in low and very-low-density lipoproteins fell abruptly, while high-density-lipoprotein cholesterol, on the contrary, increased considerably. Clinical improvement of the patients was also recorded.     

Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused most often by mutations in the vasopressin V2 receptor (AVPR2). We studied a family which included a female patient with NDI with symptoms dating from infancy. The patient responded to large doses of desmopressin (dDAVP) which decreased urine volume from 10 to 4 I/day. Neither the parents nor the three sisters were polyuric. The patient was found to be a compound heterozygote for two novel recessive point mutations in the aquaporin-2 (AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near to the NPA motif conserved in all aquaporins. Osmotic water permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2 was not increased over water control, while expression of L22V cRNA increased the Pf to approximately 60% of that for wild-type AQP2. Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wild-type AQP2 showed endosome and plasma membrane staining. Water permeability assays showed a high Pf in cells expressing wild-type and L22V AQP2. This study indicates that AQP2 mutations can confer partially responsive NDI.      

Acetaminophen (paracetamol) levels in human tears.

This study was designed to measure acetaminophen (paracetamol) levels in tears, and to compare it to serum levels. Paracetamol levels were measured in 20 paired tears and serum samples from 10 healthy volunteers, 1 and 2 hours after ingesting 1.5 g paracetamol. Tears were collected using glass microcapillary tubes while stimulating the conjunctiva with a small sponge placed in the lower fornix. Blood samples were taken simultaneously. The samples were analyzed for paracetamol levels using homogeneous enzyme immunoassay. Tears and serum paracetamol levels 1 hour after ingestion were 16.3 microg/mL +/- 7.2 (mean +/- SD), and 21.4 microg/mL +/- 7.7 (mean +/- SD) respectively. Tears and serum levels 2 hours after ingestion were 14.4 microg/mL +/- 7.8 (mean +/- SD), and 17 microg/mL +/- 7.6 (mean +/- SD) respectively. Tears and serum paracetamol levels of all the 20 paired samples (1 h and 2 h after ingestion) were 15.35 microg/mL +/- 7.4, and 19.25 microg/mL +/- 7.8, respectively (mean +/- SD). There was a strong and highly significant correlation between paracetamol levels in serum and in tears 1 and 2 hours after ingestion (r = 0.8, p = 0.005, r = 0.85, p = 0.002 respectively). Mean +/- SD ratio of tears/serum paracetamol levels 1 hour and 2 hours after ingestion were 0.77 +/- 0.21 and 0.81 +/- 0.25 respectively. Delta tears (difference in mean levels at 1 and 2 hours) paracetamol levels is significantly correlated with delta serum levels (r = 0.7, p = 0.025). A reliable, convenient, and feasible noninvasive method is described for measuring paracetamol in tears. There is no information in the literature about tears paracetamol secretion, and little information of tears drugs concentration.     

Adaptogen Action of Preparations from Inonutus obliquus

Pharmaceutical Chemistry Journal -