Prospective comparison of the therapeutic effect of teriparatide with that of combined vertebroplasty with antiresorptive agents for the treatment of new-onset adjacent vertebral compression fracture after percutaneous vertebroplasty.

UNLABELLED: Most post-vertebroplasty new-onset adjacent vertebral compression fractures (VCFs) occur within 2-3 months, and antiresorptive agents do not significantly reduce the risk of their occurrence. In opposite mechanism, teriparatide directly stimulates bone formation and improves bone strength and quality faster. The therapeutic effect of teriparatide is better than that of vertebroplasty combined with an antiresorptive treatment and is a potentially useful therapy for new-onset adjacent VCFs after vertebroplasty. INTRODUCTION: Following vertebroplasty, patients are at increased risk of new-onset adjacent-level VCFs. The therapeutic effect of antiresorptive agents is too slow, and they are associated with the risk of new VCFs. Teriparatide markedly increases bone formation and strength and reduces the incidence of new-onset VCFs. This prospective cohort study compared the therapeutic effects of teriparatide with those of combined vertebroplasty and an anti-resorber for treating new-onset adjacent VCFs after vertebroplasty. METHODS: Fifty patients with adjacent VCFs were randomly assigned to two groups: teriparatide only (group A) and additional vertebroplasty combined with an antiresorptive agent (group B). Relevant clinical data of the two groups were prospectively compared. RESULTS: The 22 patients in group A were at higher risk of new VCFs than those in group B (22 patients); they were older and had more pre-existing fractures (p < 0.05). Patients treated with teriparatide had a significantly lower incidence of new-onset VCFs (odds ratio = 0.21; 95% confidence interval, 0.02-2.10). Teriparatide-mediated VCF reduction was 78.57%, which was markedly better than that of group B. The teriparatide group had a significant decrease in the visual analog scale and an increase in the Japanese Orthopedic Association low back pain score after 6 months of treatment (p < 0.05). The increase in lumbar spine BMD was marked in the teriparatide group (21.70% vs. 6.87%) after an 18-month treatment. CONCLUSIONS: Treatment of post-vertebroplasty adjacent VCFs with teriparatide (no new vertebroplasty) was more effective than that of repeated vertebroplasties combined with an anti-resorber.

Minimally invasive vertebroplasty in the treatment of pain induced by spinal metastatic tumor.

Spinal metastatic tumor is a common problem and represents a challenging problem in oncology practice. Patients with osteolytic metastases often suffer from intractable local and/or radicular pain. Percutaneous vertebroplasty is a minimally invasive, radiologically guided procedure whereby bone cement is injected into structurally weakened vertebrae to provide immediate biomechanical stability. Vertebroplasty is also used to relieve pain by stabilizing metastatically compromised vertebrae that are at risk of pathological burst fracture. In this retrospective study, a total of 57 patients (78 vertebrae) with spinal metastatic tumor were treated with PMMA vertebroplasty. The mean value of the visual analogue scale (VAS) was 8.1 +/- 0.67 preoperatively, and significantly decreased to 3.8 +/- 1.9 (1-8, p < 0.015) one day after vertebroplasty. The mean VAS value 6 months after vertebroplsty was 2.8 +/- 2.0 (p < 0.001). Mean injected bone cement amount in our study is 5.16 +/- 1.6 mL. The complication rate is about 21.8%, bone cement extravasation without neurological deficit is the most common complication. No new or adjacent vertebral fracture has occurred in more than 2 years follow-up. Percutaneous vertebroplasty is a minimally invasive procedure that offers a remarkable advantage of effective and immediate pain relief with few complications.

Natural abundance heteronuclear NMR studies of the T3 mini-loop hairpin in the terminal repeat of the adenoassociated virus 2.

A DNA hairpin containing a T3 loop, as occurs in the terminal repeat of a popular gene therapy vector (Adenoassociated Virus 2, AAV2), has been extensively studied using homo- and heteronuclear NMR experiments. Almost complete assignment of the proton and carbon resonances, including H5'(Pro-S) and H5'(Pro-R) protons, has been accomplished at natural abundance. NOESY spectra in H2O and D2O have revealed many unusual NOEs, which, when combined with the epsilon, beta, gamma, and chi torsion angles determined from heteronuclear 1H-13C, 1H-31P, and 13C-31P coupling constants, have allowed for a more detailed picture of the T3 mini-loop hairpin. The three loop thymidines are all unpaired, yet are highly structured when bracketed by a 5'-GC...GC-3' stem sequence. The structure determined in this manuscript is considerably different from several other structures reported so far. Contrary to an RNA oligomer with a central U3 sequence that has the tendency to form a duplex with three U*U mismatches, the d(GAAGC-TTT-GCTTC) sequence exists mostly as a hairpin under millimolar NMR conditions. Since T3 triloop was found to be an essential element for the site-specific non-homologous integration of the AAV2 virus, and modification of the T3 loop residue abolishes such capability, the structure we report here may be of biological significance.

Growth, pigment production and protease activity of Monascus purpureus as affected by salt, sodium nitrite, polyphosphate and various sugars.

The effect of different levels of salt, sodium nitrite, polyphosphate and various sugars on growth, pigment production, protease activity and culture pH caused by Monascus purpureus was studied in broth medium and ground meat. The addition of sodium chloride (> 50.0 g l(-1)) and polyphosphate (> 3.0g l(-1)) to broth medium decreased mycelial growth, pigment production and protease activity of M. purpureus, whereas low concentrations of sodium nitrite (< 0.2 g l(-1)) promoted mycelial growth and pigment production. When the basal medium and ground meat contained salt, 150.0 g l(-1), the mould growth was stopped. The medium with fructose as carbon source proved to be the most suitable for mycelium growth and pigment production, with maltose and glucose being the second most productive. When sucrose and lactose were used as carbon sources, mycelium growth and pigment production were inhibited but the protease activity increased significantly. The mould showed more tolerance to salt and polyphosphate in ground meat than in broth medium and used sucrose as a carbon source as well as glucose for growth and pigment production in the meat mixture.

Stable formation of a pyrimidine-rich loop hairpin in a cruciform promoter.

We have determined the solution structure of a TCC-loop hairpin in the cruciform promoter for the bacteriophage N4 virion RNA polymerase (N4 vRNAP). This hairpin and its complementary GGA-loop hairpin are extruded at physiological superhelical density and are required for vRNAP recognition. Contrary to its complementary GGA-loop, the three pyrimidines in the TCC-loop are all unpaired. However, with the help of two juxtaposed stem Watson-Crick G.C base-pairs, each nucleotide in the loop employs a special method to stabilize the hairpin structure. The resulting structures display extensive loop base-stacking rearrangement yet minor backbone distortion, which is largely accomplished through some loop zeta and alpha torsional angle changes. Consistent with the structural studies, UV melting of the GAAGCTCCGCTTC hairpin revealed a higher melting temperature (66 degrees C) than that of the GAACGTCCCGTTC hairpin (58 degrees C) with reversed stem G.C base-pairs, indicating significant contribution from the extra three loop-stem H-bonds. Thermodynamic parameters DeltaG degrees 25of the GAAGCTCCGCTTC hairpin and its complementary GAAGCGGAGCTTC hairpin are -4.1 and -4. 3 kcal/mol respectively, indicating approximately equal contribution of each hairpin to the cruciform formation of the N4 virion RNA polymerase promoter. No significant loop dynamics in the microsecond to millisecond NMR time-scale was observed, and the abundant well-defined exchangeable and non-exchangeable proton NOEs allowed us to efficiently determine a well-converged family for the final structures of the TCC-loop hairpin.

Structural studies of symmetric DNA undecamers containing non-symmetrical sheared (PuGAPu):(PyGAPy) motifs.

Interstrand purine-purine stacks originate from tandem sheared purine.purine pairing and represent one of the most important motifs in both DNA and RNA structures. Several RNA and DNA structures, solved recently in both solution and the solid state, contain these special motifs, which greatly increase the structural diversity of nucleic acid molecules. The direct evidence for the sheared purine-purine pairing at neutral pH in solution remains, however, elusive. In this manuscript, we have used high resolution NMR methods to study a series of symmetrical DNA duplexes containing two non-symmetrical 5'-(PuGAPu)/(PyGAPy)-3' motifs. Many strong- and medium-strength NOEs across the G.A base pair were detected in the H2O-NOESY spectra collected at a relatively low temperature (-5 degrees C). These NOEs, especially those from A-6NH2 to G-H1', G-H4', and G-2NH2, clearly define the proposed side-by-side sheared G.A pairing nature. Another interesting feature is the strong NOEs exhibited by the unpaired G-imino proton in the G.A pair to its own G-2NH2, which implies that G-2NH2 is involved in H-bonding with a base in the minor groove edge. The finding that non-symmetrical (PuGAPu):(PyGAPy) motif also form similarly stable structures loosens the requirement for a more restricted (PyGAPu)2 motif in forming the interstrand purine-purine stacks.

Stable sheared A.C pair in DNA hairpins.

Single-residue d(Pu1NPu2) (Pu1.Pu2=G.A, G.G or A.A) hairpin loops can be stably closed by sheared purine.purine pairs. These special motifs have been found in several important biological systems. We now extend these loop-closing base-pairs to a sheared purine. pyrimidine (A.C) pair at a neutral pH condition. High-resolution NMR spectroscopy, distance geometry, and molecular dynamics methods were used to study d(GTACANCGTAC) oligomers. Numerous idiosyncratic nuclear Overhauser enhancements, especially those across the A.C base-pair between C4NH2left and right arrow AH1', C4NH2left and right arrow AH2, and CH5left and right arrow AH2 proton pairs, clearly define the novel sheared nature of the closing A.C base-pair. This novel base-pair is possibly present in several biological systems and in two single-stranded DNA aptamers selected from oligonucleotide libraries.

Cross-strand purine-pyrimidine stack and sheared purine.pyrimidine pairing in the human HIV-1 reverse transcriptase inhibitors.

Cross-strand homo purine-purine (G-G or A-A) stacks and sheared purine.purine pairing have been found to be important motifs in nucleic acid duplex structures. We now report novel cross-strand purine-pyrimidine (A-C) and hetero purine-purine (G-A) stacks that are established from a sheared purine.pyrimidine (A.C) pair adjacent to a sheared G.A pair in the 5'-AA/GC-3' sequence. This "internal loop" sequence is conserved in two families of single-stranded DNA inhibitors of the reverse transcriptase of type 1 human immunodeficiency virus. The distorted backbone of these inhibitors, resulting from the unique helical twists and kinks in the 5'-AA/GC-3' sequence, may be responsible for the increased affinities of these single-stranded DNA inhibitors as compared with other regular B-form duplex substrates. Two simple rules have been generalized to account for all reported cross-strand stacks.

Maternal age-specific risk of Down syndrome in an Asian population: a report of the Taiwan Down Syndrome Screening Group.

This study is a novel approach in establishing the maternal age-specific risk for Down syndrome screening in an Asian population. The relative frequency by one-year maternal age interval in women who had live births in the Taiwan area between 1975 and 1995 was used as the age-specific distribution of women who had unaffected pregnancies. Data about Down syndrome live births were obtained from the Taiwan Down Syndrome Association to establish the age distribution of women who had Down syndrome live births. The relative frequencies and the likelihood ratio by one-year maternal age interval was calculated and smoothed by running median and moving average smoothing methods. The age-specific risk was established by multiplying the total population risk by the likelihood ratio of the specific maternal age. The total live births in the Taiwan area between 1975 and 1995 were 7,232,689. A total of 527 cases of Down syndrome live births were registered in the Taiwan Down Syndrome Association. A total of 466 cases (88.43 per cent) of Down syndrome live births occurred before age 35, which was higher than occidental reports. This study established the first sizeable database of maternal age-specific risk for Down syndrome in an Asian population.

[Effectiveness of videotape education for mothers of prematurity].

To investigate the effectiveness of an educational videotape on preterm mothers' knowledge, confidence, perceived stress, and social support, mothers who had given birth prematurely were recruited to participate in this study. Sixty-two mothers were randomly assigned to a control or experimental group. During hospitalization, mothers assigned to the experimental group received additional educational videotape which was designed by researchers for this particular study, regarding the knowledge and skills of caring for premature infants. While mothers in the control group received routine educational care. Both groups of mothers filled out the questionnaire including knowledge of prematurity, maternal confidence, perceived stress and perceived social support at three time periods (before discharge, one week after discharge, and one month after discharge). The findings indicated that mothers who received a videotape education reported having higher knowledge and confidence of caring for their preterm babies than mothers who were in the control group. Moreover, mothers in the experimental group perceived lower stress than the control group mothers when their babies were one month old. The scores of perception of stress, parity, and receiving a videotape education are the best predictors to maternal confidence a week after discharge. Further, the mothers' perception of stress, parity, and the perception of social support can predict and explain 47.1% of the variance of the maternal confidence. These results can apply to clinical practice for nursing mothers who have given preterm births. A convenient videotape education can improve mothers' knowledge and confidence of caring for their premature babies at home.

Calculating three-dimensional molecular structure of paliurine B from atom-atom distance and restrained energy minimization.

The conformation of paliurine B, a 13-membered cyclopeptide alkaloid isolated from Paliurus ramosissimus, has been determined from 2D NMR and distance geometry, followed by the restrained energy minimization calculation. The conformation of the 13-membered ring is well-defined but that of the acyclic dipeptide tail region is relatively disordered. In addition, the cavity in the 13-membered ring is just large enough to insert a magnesium ion but is a little small for calcium or sodium ions.

NMR study of the solution conformation of actinomycin D.

The solution conformation of actinomycin D, the Gram-positive antibiotic and DNA-binding drug, has been determined by 1H-NMR in deuterated dimethyl sulfoxide. The structure determination is based on the experimental data set of NOE restraints. Four structures were obtained from the distance geometry and restrained molecular dynamics calculation. The resultant structures satisfy the experimental restraints very well. These structures are found to be compatible with the X-ray crystal structures.