Hyaline Membrane Disease Of Newborn Research Articles

Analysis of Efficacy of Hyaline Membrane Disease of Newborn Treated with Pulmonary Surfactant by Endotracheal Instillation

Objective To study the efficacy and safety of pulmonary surfactant used in hyaline membrane disease(HMD)of newborn treatment.Methods 67 cases of HMD children were treated.And pulmonary surfactant was used by intratracheal instillation.Clinical manifestation,blood gas analysis,X-ray chest film and complication before and after treatment were observed and recorded.Results 65 cases of children were recovered and discharged(97.01％),while 2 cases were dead.The PO2 increased significantly after the surfactant was given(P＜0.05),while the PCO2 decreased significantly(P＜0.05),and situation of skin cyanosis was relieved.X-ray chest films in 24 hours showed that 62 cases were improved(92.54％),while 4 cases were not obvious(5.97％),and there was hemorrhage image in the last 1 caes(1.49％).There were 5 cases of complication,involving 3 cases of pneumonia,1 case of intracranial hemorrhage and 1 case of pulmonary hemorrhage.Conclusion Clinical symptoms could be impurved rapidly,pulmonary oxygenation could be ameliorated,the need of mechanical ventilation could be lower and the rate of incidence of complication and death could be reduced effectively by using pulmonary surfactant early. Key words: Pulmonary surfactant; Hyaline membrane disease of newborn; Infant,newborn; Blood gas analysis

The chaperone activity and toxicity of ambroxol on Gaucher cells and normal mice

Gaucher disease (GD), caused by a defect of acid β-glucosidase (β-Glu), is one of the most common sphingolipidoses. Recently, ambroxol, an FDA-approved drug used to treat airway mucus hypersecretion and hyaline membrane disease in newborns, was identified as a chemical chaperone for GD. In the present study, we investigated the chaperone activity and toxicity of ambroxol on both cultured GD patient cells and normal mice. We found that ambroxol treatment significantly increased N370S, F213I, N188S/G193W and R120W mutant β-Glu activities in GD fibroblasts with low cytotoxicity. Additionally, we measured the β-Glu activity in the tissues of normal mice which received water containing increasing concentrations of ambroxol ad libitum for one week. No serious adverse effect was observed during this experiment. Ambroxol significantly increased the β-Glu activity in the spleen, heart and cerebellum of the mice. This result showed its oral availability and wide distribution and chaperone activity in the tissues, including the brain, and its lack of acute toxicity. These characteristics of ambroxol would make it a potential therapeutic chaperone in the treatment of GD with neurological manifestations.

Identification and Characterization of Ambroxol as an Enzyme Enhancement Agent for Gaucher Disease

Gaucher disease (GD), the most prevalent lysosomal storage disease, is caused by a deficiency of glucocerebrosidase (GCase). The identification of small molecules acting as agents for enzyme enhancement therapy is an attractive approach for treating different forms of GD. A thermal denaturation assay utilizing wild type GCase was developed to screen a library of 1,040 Food and Drug Administration-approved drugs. Ambroxol (ABX), a drug used to treat airway mucus hypersecretion and hyaline membrane disease in newborns, was identified and found to be a pH-dependent, mixed-type inhibitor of GCase. Its inhibitory activity was maximal at neutral pH, found in the endoplasmic reticulum, and undetectable at the acidic pH of lysosomes. The pH dependence of ABX to bind and stabilize the enzyme was confirmed by monitoring the rate of hydrogen/deuterium exchange at increasing guanidine hydrochloride concentrations. ABX treatment significantly increased N370S and F213I mutant GCase activity and protein levels in GD fibroblasts. These increases were primarily confined to the lysosome-enriched fraction of treated cells, a finding confirmed by confocal immunofluorescence microscopy. Additionally, enhancement of GCase activity and a reduction in glucosylceramide storage was verified in ABX-treated GD lymphoblasts (N370S/N370S). Hydrogen/deuterium exchange mass spectrometry revealed that upon binding of ABX, amino acid segments 243-249, 310-312, and 386-400 near the active site of GCase are stabilized. Consistent with its mixed-type inhibition of GCase, modeling studies indicated that ABX interacts with both active and non-active site residues. Thus, ABX has the biochemical characteristics of a safe and effective enzyme enhancement therapy agent for the treatment of patients with the most common GD genotypes.

Phosphatidylglycerol determination in the amniotic fluid from a PAD placed over the vulva: a method for diagnosis of fetal lung maturity in cases of premature ruptured membranes.

Four hundred and forty seven pregnant women with ruptured membranes, were prospectively studied in order to assess the diagnostic capacity of Phosphatidylglycerol (PhG) determination in amniotic fluid recovered from vulval pads in the diagnosis of Hyaline Membrane Disease (HMD). The identification of PhG was performed using one dimensional silica gel thin layer chromatography. The sensitivity of PhG determination in the diagnosis of HMD in newborns of the total population was found to be 88.2%, with a specificity of 76.9%. In the study population, the incidence of HMD was 7.6%, the negative predictive value was 98.8% and, the positive predictive value was 24.0%. When the 265 newborns of the gestational age group of less than or equal to 34 weeks is considered, we observed an incidence of HMD of 12.1%. The diagnostic capacity of PhG in this group was shown by a sensitivity of 87.5%, a specificity of 76.4%, a positive predictive value of 33.7% and a negative predictive value of 97.8%. This method of assessment of fetal lung maturity has a diagnostic capability similar to that described by other authors, who used amniotic fluid obtained vaginally or transabdominally. The procedure described here of amniotic fluid collection is non-invasive, harmless to the mother and fetus and simple to perform. The characteristics of this method, allow serial studies of the amniotic fluid to be carried out.

Hyaline membrane disease in the newborn: Diagnosis by ultrasound

The authors report a new method of diagnosing hyaline membrane disease (HMD) in newborns: ultrasound. Babies with HMD display a specific pattern with retrohepatic hyperechogenicity on abdominal ultrasound. The specificity of the pattern was verified in 40 prematures with respiratory distress syndrome. The sign was present in 24, and in 22 of these the final diagnosis was moderate or marked HMD. In the last 2, mild HMD was suggested. The pattern was absent in the 16 others, none of whom had HMD. The pattern probably results from an ultrasound artifact: summation of multiple aerated airways surrounded by collapsed alveoli. Follow-up examinations were possible in 13 babies with HMD. Hyperechogenicity disappeared in 8 of these patients within 6-9 days and in 3 within 10-20 days; it persisted for 60 and 70 days in 2 with bronchopulmonary dysplasia. In conclusion, retrohepatic hyperechogenicity in newborns is pathognomonic for HMD and allows an instant diagnosis. The persistence of the pattern could be a useful criterion for evaluation of the prognosis.

Effects of oxidant air pollutants on pulmonary surfactant using two isolation procedures.

Approximately three decades ago, pulmonary surfactant (PS) was shown to lower the surface tension of the liquid layer lining the lung's alveolar surface. It is important in preventing alveolar collapse and pulmonary edema and abnormalities is PS are associated with hyaline membrane disease in newborns and respiratory distress syndrome in adults. A number of studies have investigated the effects of oxidant exposure on the chemical composition of lavage fluids from which cellular debris has been removed by low speed centrifugation; however, few of these studies have incorporated additional centrifugation steps for isolation of PS from the lavage fluid. The goal of our work was to determine whether or not additional centrifugation steps in the isolation of PS from the lavage fluid would alter either the fatty acid composition, or the observed changes in it, on exposure to the combination of the air pollutants, O{sub 3} and NO{sub 2}. We found that both the initial composition and the observed changes on exposure were sensitive to the use of additional sucrose density gradient centrifugation (SDGC) steps.