ABSTRACT
Diabetic retinopathy and acromegaly are diseases associated with excess action of GH and its effector IGF-I, and there is a need for improved therapies. We have designed an optimised 2'-O-(2-methoxyethyl)-modified phosphorothioate oligodeoxynucleotide, ATL 227446, and demonstrated its ability to suppress GH receptor mRNA in vitro. Subcutaneous injections of ATL 227446 reduced GH receptor mRNA levels, GH binding activity and serum IGF-I levels in mice after seven days of dosing. The reduction in serum IGF-I could be sustained for over ten weeks of dosing at therapeutically relevant levels, during which there was also a significant decrease in body weight gain in antisense-treated mice relative to saline and mismatch control-treated mice. The findings indicate that administration of an antisense oligonucleotide to the GH receptor may be applicable to human diseases in which suppression of GH action provides therapeutic benefit.
Subject(s)
Insulin-Like Growth Factor I/analysis , Oligonucleotides, Antisense/administration & dosage , Oligonucleotides/administration & dosage , Receptors, Somatotropin/analysis , Weight Gain/drug effects , Animals , Cells, Cultured , Gene Expression/genetics , Growth Hormone/metabolism , Injections, Subcutaneous , Insulin-Like Growth Factor I/antagonists & inhibitors , Liver/cytology , Liver/metabolism , Male , Mice , Mice, Inbred BALB C , RNA, Messenger/analysis , Receptors, Somatotropin/antagonists & inhibitorsABSTRACT
Inicialmente, la esteatohepatitis se consideró expresión exclusiva del abuso crónico de alcohol, hasta hace algunos años considerada una entidad poco común, los últimos estudios muestran que la esteatohepatitis no alcoholica, es el diagnóstico más común en pacientes que presentan anormalidades persistentes en los exámenes laboratoriales de función hepática.
Subject(s)
Humans , Male , Female , Alcoholism , BoliviaABSTRACT
A retrospective study of the newborns who were submitted to mechanical ventilation at the Neonatal Intermediate Care Unit was made between July 1991 and June 1994. Mechanical ventilation in such a unit should be transitory and not exceed 24 hours. Information concerning pregnancy, labour, neonates, type of ventilation and its problems was gathered. Forty seven neonates were ventilated. The average ventilation time was six hours (1-20 hours). The main cause of ventilation was hyaline membrane disease which occurred in 24% of all cases. Mortality observed was 16.6% and some sequellae were registered which were related not only to ventilation but also to the basic pathology in 26% of cases.
