Lung development and the pulmonary surfactant system: Hormonal influences

The effect of hormones on developmental events is not a new area of scientific investigation. However, in the last decade, the developing lung has been the focus of an increasing amount of basic and applied research. Inadequate development of the newborn's respiratory system precludes extrauterine existence; indeed, such respiratory inadequacy has been a leading cause of death in premature infants. Tremendous strides have been made in understanding the basic cell biology of the developing lung. Much has been learned about the source, composition, and function of pulmonary surfactant, a surface-active material produced by the lung and essential to alveolar stability. Deficient stores of this material is a major etiologic factor in the respiratory distress syndrome of the newborn (RDS). This fact, coupled with observations that certain hormones can accelerate lung development and the consequent availability of adequate stores of pulmonary surfactant, has led to a large body of literature dealing with the effects of hormones (and other agents) on lung development. It is the purpose of this literature review (1) to discuss the various kinds of investigations which have linked surfactant synthesis to the type II pulmonary epithelial cell; and (2) to review the current status of research dealing with the effects of glucocorticoids and thyroid hormons on lung maturation.     

Intrarater Reliability of Functional Performance Tests for Subjects With Patellofemoral Pain Syndrome

OBJECTIVE: Patellofemoral pain syndrome (PFPS) is a common clinical entity seen by the sports medicine specialist. The ultimate goal of rehabilitation is to return the patient to the highest functional level in the most efficient manner. Therefore, it is necessary to assess the progress of patients with PFPS using reliable functional performance tests. Our purpose was to evaluate the intrarater reliability of 5 functional performance tests in patients with PFPS. DESIGN AND SETTING: We used a test-retest reliability design in a clinic setting. SUBJECTS: Two groups of subjects were studied: those with PFPS (n = 29) and those with no known knee condition (n = 11). The PFPS group included 19 women and 10 men with a mean age of 27.6 +/- 5.3 years, height of 169.80 +/- 10.5 cm, and weight of 69.59 +/- 15.8 kg. The normal group included 7 women and 4 men with a mean age of 30.3 +/- 5.2 years, height of 169.55 +/- 9.9 cm, and weight 69.42 +/- 14.6 kg. MEASUREMENTS: The reliability of 5 functional performance tests (anteromedial lunge, step-down, single-leg press, bilateral squat, balance and reach) was assessed in 15 subjects with PFPS. Secondly, the relationship of the 5 functional tests to pain was assessed in 29 PFPS subjects using Pearson product moment correlations. The limb symmetry index (LSI) was calculated in the 29 PFPS subjects and compared with the group of 11 normal subjects. RESULTS: The 5 functional tests proved to have fair to high intrarater reliability. Intrarater reliability coefficients (ICC 3,1) ranged from.79 to.94. For the PFPS subjects, a statistical difference existed between limbs for the anteromedial lunge, step-down, single-leg press, and balance and reach. All functional tests correlated significantly with pain except for the bilateral squat; values ranged from.39 to.73. The average LSI for the PFPS group was 85%, while the average LSI for the normal subjects was 97%. CONCLUSIONS: The 5 functional tests proved to have good intrarater reliability and were related to changes in pain. Future research is needed to examine interrater reliability, validity, and sensitivity of these clinical tests.     

Variable clinical presentation of lysosomal beta-mannosidosis in patients with null mutations

Beta-mannosidosis is an autosomal recessive lysosomal storage disease resulting from a deficiency of the lysosomal enzyme beta-mannosidase. The clinical manifestations of this disease in reported human cases are very heterogeneous ranging from relatively mild to moderately severe. This is in contrast with the severe prenatal onset seen in ruminant beta-mannosidosis. In humans, mental retardation, hearing loss, frequent infections, and behavioral problems are relatively common. Dysmorphology and skeletal involvement such as those seen in ruminants are unusual. The purpose of this study is to determine the range of clinical expression in human beta-mannosidosis resulting from null mutations. We determined that the beta-mannosidase gene consists of 17 exons. Intron-based PCR primers were designed and used to amplify each of the exons in genomic DNA isolated from patient fibroblasts. We identified two patients with null mutations. Results of the analysis showed that one patient was heterozygous for nonsense mutations G334T (E83X) in exon 2 and C1363T (Q426X) in exon 10, resulting in truncation of the deduced peptide sequence from 879 to 82 and 425 amino acids, respectively. The second patient was homozygous for a deletion mutation in exon 11 (1541delAT). This deletion causes a reading frame shift and 26 out of frame amino acids before a stop codon occurs in exon 12, resulting in truncation of the deduced peptide sequence from 879 to 510 amino acids. Because disease presentation in these patients with null mutations is very variable, ranging from mild to severe, we conclude that beta-mannosidosis in humans may indeed be milder than typical of other lysosomal storage disorders.     

Endothelial and vascular smooth muscle cell function on poly(lactic-co-glycolic acid) with nano-structured surface features

Biomaterials that successfully integrate into surrounding tissue should match not only the tissue's mechanical properties, but also its topography. The cellular response to a biomaterial may be enhanced in synthetic polymer formulations by mimicking the surface roughness created by the associated nano-structured extra-cellular matrix components of natural tissue. As a first step towards this endeavor, the goal of the present in vitro study was to use these design parameters to develop a synthetic, nano-structured, polymeric biomaterial that promotes cell adhesion and growth for vascular applications. In a novel manner, poly(lactic-co-glycolic acid) (PLGA) (50/50wt% mix) was synthesized to possess a range (from micron to nanometer) of surface features. Reduction of surface features was accomplished by treating conventional PLGA with various concentrations of NaOH for select periods of time. Results from cell experiments indicated that, compared to conventional PLGA, NaOH treated PLGA enhanced vascular smooth muscle cell adhesion and proliferation. However, PLGA prepared by soaking in NaOH decreased endothelial cell adhesion and proliferation compared to conventional PLGA. After further investigation, this finding was determined to be a result of chemical (and not topographical) changes during polymer synthesis. Surface chemistry effects were removed while retaining nano-structured topography by using polymer/elastomer casting methods. Results demonstrated that endothelial and smooth muscle cell densities increased on nano-structured cast PLGA. For these reasons, the present in vitro study provided the first evidence that nano-structured surface features can significantly improve vascular cell densities; such design criteria can be used in the synthesis of the next-generation of more successful tissue-engineered vascular grafts.     

Transdermal progesterone and its effect on vasomotor symptoms,blood lipid levels,bone metabolic markers,moods, and quality of life for postmenopausal women

OBJECTIVE: To determine whether transdermal progesterone cream has any effect on vasomotor symptoms, mood, sexual response, cardiovascular lipid levels, or bone mineral metabolic markers. DESIGN: A parallel, double-blind, randomized, placebo-controlled trial comparing the effect of a transdermal cream containing a progesterone (32 mg daily) with a placebo cream. Eighty postmenopausal women in the Menopause Centre at the Royal Hospital for Women, Sydney, were randomly allocated to receive either the progesterone cream or the placebo. They were evaluated using the Greene Climacteric Scale and the Menopause Quality of Life Questionnaire, as well as blood analysis for lipids and bone markers over a period of 12 weeks. Women were prescribed a cream containing either progesterone at 32 mg daily or a placebo cream for a period of 12 weeks. RESULTS: There was no detectable change in vasomotor symptoms, mood characteristics, or sexual feelings, nor was there any change in blood lipid levels or in bone metabolic markers, despite a slight elevation of blood progesterone levels. CONCLUSION: The use of the transdermal route to administer progesterone at 32 mg daily does not seem to allow sufficient hormone to enter the body to achieve a biological effect on lipid levels, bone mineral metabolic markers, vasomotor symptoms, or moods.