Pelvic pseudotumoral calcium pyrophosphate dihydrate deposition: an ultrastructural study

We analyzed large periarticular calcifications of the hips and pubis in a woman with diffuse primary chondrocalcinosis, symptomatic in the knees. Serial articular and periarticular biopsies were obtained during surgery for osteoporotic hip fracture. Histologic examination showed diffuse nonbirefringent clumps in red alizarin stained cartilage, capsula and tendon. Scanning electron microscopy with microanalysis indicated a calcium/phosphorus atomic ratio of about 1. Transmission electron microscopy, electron diffraction and Raman spectroscopy assessed calcium pyrophosphate dihydrate (CPPD) in cartilage, synovia, capsula, tendon and muscle. The cause of these hard to observe, bulky CPPD periarticular deposits, which resembled basic calcium phosphate on radiography, is still unclear.     

Beta-carotene in HIV infection: an extended evaluation

OBJECTIVE: Several small short-term intervention studies have suggested that beta-carotene supplementation in HIV-infected patients can increase the number of various immune cells including CD4 cells. This prospective double-blinded study was designed to investigate whether beta-carotene supplementation would result in this immuno-enhancement in a larger number of patients over a longer time period. METHODS: HIV-positive patients were randomly assigned to receive either 60 mg beta-carotene orally three times daily or a matched placebo. In addition, all patients received a multivitamin supplement. Patients were evaluated at baseline, 1 month, and 3 months for T-cell quantitative subsets, natural killer cells, HIV p24 antigen, beta-carotene levels, complete blood counts and chemistry batteries. Body weights and Karnofsky scores were evaluated at each visit. RESULTS: Seventy-two patients signed informed consent forms and entered the study. Except for serum beta-carotene concentration, there were no statistically significant differences (P < 0.05) between the treatment (60 mg beta-carotene three times daily and multivitamins) and placebo (placebo and multivitamins) groups at baseline or after either 1 or 3 months of treatment. DISCUSSION: Earlier studies suggesting that beta-carotene supplementation increased levels of immune cells in HIV-infected patients were not replicated in this study. The addition of a multivitamin supplement to both arms of this study may have masked any difference between the two groups. However, on the basis of the results of this study, we would not recommend supplementation with high doses of beta-carotene for HIV-infected patients.     

复吹转炉底吹不同气体时钢中氮的行为及吸氮动力学模拟研究

在感应炉上进行的底吹CO_2、N_2、CO_2+N_2的复吹模拟实验研究表明,熔池中氮的行为受底吹气体性质、脱碳速度和钢液氧化性的影响;钢液吸氮的动力学规律,随底吹气体的性质不同而有差别,底吹单一CO_2或N_2时,分别为二级反应和一级反应,并求得二级反应的速度常数和氮在钢液中的传质系数分别为K_(-1)=0.044(Wt%)~(-1)·cm·s~(-1),K_d=0.0308cm·s~(-1),底吹CO_2+N_2混合气体时,近似表观二级反应,其表观速度常数K_2=0.0406(Wt％)~(-1)cm·s~(-1)。     

Cyclopropane-derived peptidomimetics. Design, synthesis, evaluation, and structure of novel HIV-1 protease inhibitors

Toward establishing the general efficacy of using trisubstituted cyclopropanes as peptide mimics to stabilize extended peptide structures, the cyclopropanes 20a-d were incorporated as replacements into 9-13, which are analogues of the known HIV-1 protease inhibitors 14 and 15. The syntheses of 20a-d commenced with the Rh2[5(S)-MEPY]4-catalyzed cyclization of the allylic diazoesters 16a-d to give the cyclopropyl lactones 17a-d in high enantiomeric excess. Opening of the lactone moiety using the Weinreb protocol and straightforward refunctionalization of the intermediate amides 18a-d gave 20a-d. A similar sequence of reactions was used to prepare the N-methyl-2-pyridyl analogue 28. Coupling of 20a-d and 28 with the known diamino diol 22 delivered 9-13. Pseudopeptides 9-12 were found to be competitive inhibitors of wild-type HIV-1 protease in biological assays having Kis of 0.31-0.35 nM for 9, 0.16-0.21 nM for 10, 0.47 nM for 11, and 0.17 nM for 12; these inhibitors were thus approximately equipotent to the known inhibitor 14(IC50 = 0.22 nM) from which they were derived. On the other hand 13 (Ki = 80 nM) was a weaker inhibitor than its analogue 15 (Ki = 0.11 nM). The solution structures of 9 and 10 were analyzed by NMR spectroscopy and simulated annealing procedures that included restraints derived from homo- and heteronuclear coupling constants and NOEs; because of the molecular symmetry of9 and 10, a special protocol to treat the NOE data was used. The final structure was checked by restrained and free molecular dynamic calculations using an explicit DMSO solvent box. The preferred solution conformations of 9 and 10 are extended structures that closely resemble the three-dimensional structure of 10 bound to HIV-1 protease as determined by X-ray crystallographic analysis of the complex. This work convincingly demonstrates that extended structures of peptides may be stabilized by the presence of substituted cyclopropanes that serve as peptide replacements. Moreover, the linear structure enforced in solution by the two cyclopropane rings in the pseudopeptides 9-12 appears to correspond closely to the biologically active conformation of the more flexible inhibitors 14 and 15. The present work, which is a combination of medicinal, structural, and quantum chemistry, thus clearly establishes that cyclopropanes may be used as structural constraints to reduce the flexibility of linear pseudopeptides and to help enforce the biologically active conformation of such ligands in solution.     

六氢哒嗪中的灼烧残渣去除方法研究

六氢哒嗪制备过程中使用大量无机盐,直接导致了最终产品的灼烧残渣含量远远超标,本文研究了洗涤去除该无机盐的方法,通过该方法,可以使灼烧残渣含量小于0．01％。     

Validity of near-infrared interactance for estimating relative body fat in female high school gymnasts

The present investigation examined the validity of near-infrared interactance (NIR) estimates of relative body fat (% fat) from the Futrex-5000 (F5000), Futrex-5000A (F5000 A), and Futrex-1000 (F1000) instruments. Ninety-eight female high school gymnasts (X age+/-SD = 15.7+/-1.2 yr) participated in this investigation. Subsamples were used to cross-validate the F5000 (n = 52), F5000A (n = 46), and F1000 (n = 89) instruments. The NIR % fat estimates were validated against criterion % fat from underwater weighing (UWW) using the adult conversion constants of Brozek et al. (6) (UWWB) and the female age-specific constants of Lohman (23) (UWWL). The cross-validation statistical analysis included examination of the constant error (CE), standard error of estimate (SEE), r, and total error (TE). In addition, full-model multiple regression analyses were used to predict UWWB or UWWL from body weight (BW) and height (HT). BW and HT were correlated with % fat at R = 0.65-0.70, while the validity coefficients for the NIR instruments ranged from r = 0.40-0.78. The F5000 resulted in nonsignificant CE values (-0.3 % fat vs UWWB and 1.5 % fat vs UWWL; p > 0.008) as well as the lowest TE values (TE = 3.1 % fat vs UWWB and 4.0 % fat vs UWWL). All other NIR estimates of % fat resulted in TE values > or = 6.3 % fat. In addition, for all NIR instruments there were negative correlations for the plots of the CE versus the mean of predicted and criterion (UWWB and UWWL) % fat. Therefore, the present findings indicated that the F5000 provided more accurate estimates of % fat than the F5000A or F1000 instruments, but may underestimate the desired minimal body weight for female gymnasts at the low end of the % fat distribution.     

Nephrotoxic potential of 2-amino-5-chlorophenol and 4-amino-3-chlorophenol in Fischer 344 rats: comparisons with 2- and 4-chloroaniline and 2- and 4-aminophenol

Nephrotoxicity occurs following intraperitoneal (i.p.) administration of 2-chloroaniline or 4-chloroaniline hydrochloride to Fischer 344 rats, but the nephrotoxicant chemical species and mechanism of nephrotoxicity are unknown. The purpose of this study was to evaluate the in vivo and in vitro nephrotoxic potential of 2-amino-5-chlorophenol and 4-amino-3-chlorophenol, metabolites of 4-chloroaniline and 2-chloroaniline. A comparison was also made between the nephrotoxic potential of the aminochlorophenols and the corresponding aminophenols to examine the effect of adding a chloride group on the nephrotoxic potential of the animophenols. Male Fischer 344 rats (4/group) were given an i.p. injection of a chloroaniline or aminochlorophenol hydrochloride (1.5 mmol/kg), and aminophenol (1.0 or 1.5 mmol/kg), or vehicle, and renal function monitored at 24 and 48 h. Both aminochlorophenols induced smaller and fewer renal effects that the parent chloroanilenes in vivo. Also, 4-aminophenol was markedly more potent as a nephrotoxicant that 4-amino-3-chlorophenol, while 2-aminophenol and 2-amino-5-chlorophenol induced only mild change in renal function. In vitro, the phenolic compounds reduce p-aminohippurate accumulation by renal cortical slices at bath concentrations of 0.01 mM, while a bath concentration of 0.50 mM or greater was required for the chloroanilines. However, all compounds reduced tetraethylammonium accumulation at bath concentrations of 0.1-0.5 mM or greater. These results indicate that extrarenally-produced aminochlorophenol metabolites do not contribute to the mechanism of chloroaniline nephrotoxicity. Also, the reduced nephrotoxic potential of 4-amino-3-chlorophenol compared to 4-aminophenol could result from an altered ability of the aminochlorophenol to redox cycle or form conjugates.