Direct modulation by androgens of the response of human bone cells (SaOS-2) to human parathyroid hormone (PTH) and PTH-related protein

We have reported previously that 17 beta-estradiol (E2) inhibits selectively the cAMP response to human (h) PTH and PTH-related protein (hPTHrP), but not to vasoactive intestinal peptide, in human osteoblast-like cells (SaOS-2). We have now extended these studies to investigate the actions of androgens on hPTH-stimulated accumulation of cAMP, and on the roles of new protein synthesis and pertussis toxin (PTox) substrates in the actions of steroid hormones on SaOS-2 cells. Pretreatment with testosterone (T) or 5 alpha-dihydrotestosterone (5 alpha-DHT) for 4-12 h at concentrations of 10(-12) to 10(-8) M inhibited significantly the cAMP response to hPTH by up to 50-70% of control. Like E2, the actions of T and 5 alpha-DHT were selective for hPTH or hPTHrP; there was no inhibition of the stimulatory action of vasoactive intestinal peptide. Two related steroids, 5 beta-DHT and 17 alpha-epitestosterone, did not inhibit the action of hPTH. Pretreatment of cells with cycloheximide, under conditions which inhibited protein synthesis by greater than 90%, reduced the cAMP response to hPTH but did not block the further inhibitory actions of E2, T, or 5 alpha-DHT. Pretreamtent of cells with PTox (100 ng/ml) for 24 h, enhanced the accumulation of cAMP stimulated by hPTH consistent with an action of PTox on Gi; however, the inhibitory actions of E2, T, and 5 alpha-DHT on PTH-stimulated cAMP accumulation were not attenuated by PTox. We conclude that androgens, as well as estrogens, act directly on human bone cells to modulate selectively an early effect of hPTH. The inhibitory actions of these steroid hormones do not appear to depend on new protein synthesis and may not involve a functionally active PTox substrate, presumably Gi.     

pH-dependent effects of lidocaine on defibrillation energy requirements in dogs

Lidocaine increases the energy required for ventricular defibrillation in dogs. Because sodium channel-blocking agents that are weak bases have pH-dependent electrophysiologic effects, we investigated the pH dependence of lidocaine (pKa, 7.9) on internal defibrillation energy requirements in 28 dogs with atrial spring and left ventricular patch electrodes. Results of defibrillation testing were used to derive 50% and 90% successful energy requirements (ED50 and ED90) using logistic regression and were compared with analysis of variance. Acidosis produced by hydrochloric acid infusion decreased the arterial pH from 7.40 +/- 0.05 (SD) to 7.18 +/- 0.03 (n = 8, p less than 0.01), but no significant change in ED90 was observed (14 +/- 4 to 16 +/- 6 J). Lidocaine infusion to therapeutic levels (4.2 +/- .07 micrograms/ml) at normal pH (7.42 +/- 0.02) increased ED90 from 13 +/- 3 to 17 +/- 3 J (n = 6, p less than 0.05), and subsequent acidosis (pH 7.19 +/- 0.02, p less than 0.01) exacerbated this effect of lidocaine on ED90 (22 +/- 5 J, p less than 0.05). Alkalosis produced by respirator hyperventilation increased the arterial pH from 7.41 +/- 0.03 to 7.60 +/- 0.03 (n = 8, p less than 0.01), with a fall in ED90 from 13 +/- 4 to 8 +/- 3 J (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Severe erythroblastopenia and hemolytic anemia during a hepatitis A infection

A 41-year-old woman had acute hepatitis A infection complicated with severe anemia due to selective erythroblastopenia and hemolysis. A mechanism involving a cellular immune reaction is suggested. The hematological complications resolved during steroid treatment. She later developed a transient seropositive arthritis.     

The use of pelvic ultrasonography in the evaluation of adolescents with pelvic inflammatory disease

To evaluate the use of pelvic ultrasonography in the diagnosis and management of female adolescents with pelvic inflammatory disease (PID), sonograms of 60 patients with PID were compared with those of 40 age-matched controls. Sonograms were evaluated for adnexal volume, adnexal adherence, uterine size, and the presence of cul-de-sac fluid. Eleven (19.3%) of the 57 patients with PID, in whom adequate sonograms were obtained, had tubo-ovarian abscesses; in seven of these patients, the abscesses were diagnosed ultrasonographically before suspected clinically. Even in those patients without tubo-ovarian abscesses, the mean (+/- SD) adnexal volume in the PID group was significantly larger than that of the control group (11.0 +/- 6.8 cm3 vs 5.2 +/- 2.7 cm,3 respectively). Adnexal adherence, uterine size, and the presence of cul-de-sac fluid were not useful in differentiating patients with PID from normal controls. Pelvic ultrasonography can be a useful adjunct in the diagnosis and management of PID in adolescents and may, in some instances, provide diagnoses in the absence of clinical findings.     

A randomized multicenter study to determine the efficacy of activity restriction for preterm labor management in patients testing negative for fetal fibronectin.

OBJECTIVE: To assess the impact of activity restriction (AR) on the incidence of preterm birth in women treated for preterm labor testing negative for fetal fibronectin (fFN). STUDY DESIGN: Women who were diagnosed with preterm labor and tocolyzed with magnesium sulfate were concurrently screened with fFN for the purpose of subsequent management. Included were consenting patients with negative fFN, gestational age 23 0/7-33 6/7 weeks, cervical dilation < or =3 cm, and minimal vaginal bleeding. Patients were randomized to AR or no AR. Primary study outcome was incidence of preterm delivery and interval from randomization to delivery. RESULTS: A total of 73 women with negative fFN were randomized (36 with AR, 37 without AR). The overall preterm birth rate was 40%, with 44.4% of patients with AR and 35.1% of patients without AR delivering preterm, p=0.478. CONCLUSION: Maternal AR did not impact pregnancy outcome. The incidence of preterm birth in symptomatic women testing fFN negative was higher than previously reported.     

Novel azapeptide inhibitors of cathepsins B and K. Structural background to increased specificity for cathepsin B

Abstract: We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, K_i, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe ( 7 ) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7 . We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K.     

Functional results of the surgery of esophageal opening hernia]

The article presents an original method of laparoscopic anti-reflux surgery, immediate and long-term results of the treatment of 132 patients with esophageal opening hernia. It also describes the analysis of the life quality of patients with the gastroesophageal reflux disease before and after the surgery.     

Monte Carlo assessment of soil moisture effect on high-energy thermal neutron capture gamma-ray by 14N.

Among many conventional techniques, nuclear techniques have shown to be faster, more reliable, and more effective in detecting explosives. In the present work, neutrons from a 5 Ci Am-Be neutron source being in water tank are captured by elements of soil and landmine (TNT), namely (14)N, H, C, and O. The prompt capture gamma-ray spectrum taken by a NaI (Tl) scintillation detector indicates the characteristic photo peaks of the elements in soil and landmine. In the high-energy region of the gamma-ray spectrum, besides 10.829 MeV of (15)N, single escape (SE) and double escape (DE) peaks are unmistakable photo peaks, which make the detection of concealed explosive possible. The soil has the property of moderating neutrons as well as diffusing the thermal neutron flux. Among many elements in soil, silicon is more abundant and (29)Si emits 10.607 MeV prompt capture gamma-ray, which makes 10.829 MeV detection difficult. The Monte Carlo simulation was used to adjust source-target-detector distances and soil moisture content to yield the best result. Therefore, we applied MCNP4C for configuration very close to reality of a hidden landmine in soil.