Effect of liposomal methylprednisolone on heart allograft survival and immune function in rats

Liposomal methylprednisolone (L-MPL) applied in monotherapy prolonged cardiac allograft survival in rats in comparison with the same dosage regimen of drug in solution (Solu-Medrol). The most efficacious treatment consisted of a 2-mg/kg i.v. dose of L-MPL twice a week (group III), producing survival up to 30 days, followed by a 4-mg/kg/week dose of L-MPL (group IV) and a single 2-mg/kg dose of L-MPL (group II). Survival in animals receiving Solu-Medrol as a 2-mg/kg dose twice a week (group V) did not differ from untreated animals. Only daily 4-mg/kg doses of methylprednisolone (MPL) in solution (group VI) were as effective as group III. The concentrations of MPL in liver and spleen were detectable for 26 days after the last dose of L-MPL, showing tissue selective sequestration of drug. Treatment at these low doses did not suppress endogenous corticosterone determined 24 hr or later in plasma. The administration of steroid caused significant immunosuppression in most animals as measured by inhibition of splenocyte blastogenesis induced with phytohemagglutinin. Cellular immunity data did not differ significantly between groups, but alterations occurred at day 14 to 15 after surgery: CD3, CD4 and ratio CD4:CD8 subsets of cells showed minimum values; CD8, CD4CD8, CD25 and white blood cell counts were at maximum at this time. Slight but significant differences between Immunoglobulin M suppression in group II compared to group I or V were found, whereas Immunoglobulin G values were unchanged. The transplantation and treatment with steroid decreased the total body weight of animals but increased weights of internal organs, particularly spleen, similarly for all groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antibodies to proteinase 3 mediate expression of vascular cell adhesion molecule-1 (VCAM-1)

Although much is known about the characteristics of employees who smoke cigarettes, very little is known about workers who use smokeless tobacco. The current study was designed to understand the characteristics of smokeless tobacco users in relation to their performance at work and compare them with smokers and former tobacco users. Data were collected via interviews and questionnaires from a random sample of employees working at Pacific Lumber Company (N = 146), the largest single-site lumber mill in California. A total of 63 smokeless tobacco users (21 of whom also smoked cigarettes), 43 cigarette smokers, and 40 employees who had successfully quit using tobacco (34 of whom previously used cigarettes only) provided information about their health behavior, quality of work life, and performance at work. Analyses revealed that smokeless tobacco users reported less healthful sleep patterns, drank alcohol more often, were intoxicated more often, reported less job satisfaction and organizational commitment, and reported that both chewers and smokers do not work as hard and take more breaks than do tobacco-free employees (quitters). Specific differences among chewers-only, smokers-only, smokers-and-chewers, and quitters are presented. Results suggest the organizational value of developing worksite cessation programs for smokeless tobacco users.     

Maturation alters the contractile role of calcium in ovine basilar arteries

OBJECTIVE: To investigate the distribution patterns of primary and permanent teeth in the cleft area and the numerical variation in teeth in unilateral complete cleft lip and palate (UCLP) patients. DESIGN: A survey of the dentition in UCLP patients. SETTING: Craniofacial Center, Chang Gung Memorial Hospital, Taipei, Taiwan. PATIENTS: 137 UCLP patients who met the following criteria: (1) have had at least one panoramic film taken, (2) the first panoramic film illustrates either primary or early mixed dentition. Evaluation of both permanent and primary dentition was available in 91 cases. MAIN OUTCOME MEASURES: Two evaluators performed independent evaluations of number and distribution of teeth in UCLP patients. The hypothesis that there are two odontogenic origins for maxillary lateral incisors was proposed to explain the occurrence of distribution patterns of dentition in the cleft area and to explain differences between primary and permanent dentition in UCLP patients. RESULTS: Four distribution patterns in the cleft area were identified in both the primary and the permanent dentition. In the primary dentition, placement of the lateral incisor distal to the alveolar cleft was the predominant pattern (pattern y, 82.4%), followed by absence of the cleft side maxillary lateral incisor (pattern ab, 9.9%), presence of one tooth on each side of the alveolar cleft (pattern xy, 5.5%), and placement of the lateral incisor mesial to the alveolar cleft (pattern x, 2.2%). In the permanent dentition, the most common pattern was the absence of the maxillary lateral incisor on the cleft side (pattern AB, 51.8%), followed by lateral incisor placement distal to the alveolar cleft (pattern Y, 46%), lateral incisor placement mesial to the alveolar cleft (pattern X, 1.5%) and the presence of one tooth on each side of the alveolar cleft (pattern XY, 0.7%). The discrepancy between the distribution patterns of primary dentition and permanent dentition successors is 57.1%. Variations in tooth number in both primary and permanent dentition of UCLP patients occurred most often in the cleft area. Abnormalities in the number of teeth (hypodontia or hyperdontia) outside the cleft area were more common in the permanent dentition than in the primary dentition (24.1% versus 4.4%). CONCLUSIONS: Four distribution patterns in the cleft area were identified in both sets of dentition. Our findings of distribution patterns in UCLP patients support the hypothesis that there may be two odontogenic origins for maxillary lateral incisors. Clinicians involved in managing the dentition of UCLP patients should consider the high frequency of numerical variation both in and outside the cleft area before starting dental treatment.     

Neurologic disease among women with breast implants

US angiography, enhanced with intraarterial CO2 microbubbles imaging, documented 40 nodules of hepatocellular carcinoma (HCC) lesser than 20 mm in diameter in 34 patients, which were convinced histopathologically. As to the imaging acuity of arterial vascularity in nodules, US angiography was compared with DSA and US color angio. The detection of arterial vascularity was possible in 34 (85.0%) of 40 nodules by US angiography, 26 (65.0%) by DSA, and 28 (70.0 %) by US color angio. US angiography was available for detection of HCC, particularly with small HCC lesser than 20 mm in size.     

Peptide agonist of the thrombopoietin receptor as potent as the natural cytokine

Two families of small peptides that bind to the human thrombopoietin receptor and compete with the binding of the natural ligand thrombopoietin (TPO) were identified from recombinant peptide libraries. The sequences of these peptides were not found in the primary sequence of TPO. Screening libraries of variants of one of these families under affinity-selective conditions yielded a 14-amino acid peptide (Ile-Glu-Gly-Pro-Thr-Leu-Arg-Gln-Trp-Leu-Ala-Ala-Arg-Ala) with high affinity (dissociation constant approximately 2 nanomolar) that stimulates the proliferation of a TPO-responsive Ba/F3 cell line with a median effective concentration (EC50) of 400 nanomolar. Dimerization of this peptide by a carboxyl-terminal linkage to a lysine branch produced a compound with an EC50 of 100 picomolar, which was equipotent to the 332-amino acid natural cytokine in cell-based assays. The peptide dimer also stimulated the in vitro proliferation and maturation of megakaryocytes from human bone marrow cells and promoted an increase in platelet count when administered to normal mice.     

Monohydroxyethylrutoside, a dose-dependent cardioprotective agent, does not affect the antitumor activity of doxorubicin

The cumulative dose-related cardiotoxicity of doxorubicin is believed to be caused by the production of oxygen- free radicals. 7-Monohydroxyethylrutoside (monoHER), a semisynthetic flavonoid and powerful antioxidant, was investigated with respect to the prevention of doxorubicin-induced cardiotoxicity in mice and to its influence on the antitumor activity of doxorubicin in vitro and in vivo. Non-tumor-bearing mice were equipped with a telemeter in the peritoneal cavity. They were given six weekly doses of 4 mg/kg doxorubicin i.v., alone or in combination with either 100 or 250 mg/kg monoHER i.p., 1 h prior to doxorubicin administration and for the following 4 days. Cardiotoxic effects were measured from electrocardiogram changes up to 2 weeks after treatment. Protection against cardiotoxicity was found to be dose dependent, with 53 and 75% protection, respectively, as calculated from the reduction in the increase in the ST interval. MonoHER and several other flavonoids with good antioxidant properties were tested for their antiproliferative effects in the absence or the presence of doxorubicin in A2780 and OVCAR-3 human ovarian cancer cells and MCF-7 human breast cancer cells in vitro. Some flavonoids were directly toxic at 50 and 100 microM, whereas others, including monoHER, did not influence the antiproliferative effects of doxorubicin at these concentrations. The influence of monoHER was further tested on the growth-inhibitory effect of 8 mg/kg doxorubicin i.v., given twice with an interval of 1 week in A2780 and OVCAR-3 cells that were grown as s.c. xenografts in nude mice. MonoHER, administered 1 h before doxorubicin in a dose schedule of 500 mg/kg i.p. 2 or 5 days per week, was not toxic and did not decrease the antitumor activity of doxorubicin. It can be concluded that monoHER showed a dose-dependent protection against chronic cardiotoxicity and did not influence the antitumor activity of doxorubicin in vitro or in vivo.     

Tyrosine structural changes detected during the photoactivation of rhodopsin

We present the first Fourier transform infrared (FTIR) analysis of an isotope-labeled eukaryotic membrane protein. A combination of isotope labeling and FTIR difference spectroscopy was used to investigate the possible involvement of tyrosines in the photoactivation of rhodopsin (Rho). Rho --> MII difference spectra were obtained at 10 degrees C for unlabeled recombinant Rho and isotope-labeled L-[ring-2H4]Tyr-Rho expressed in Spodoptera frugiperda cells grown on a stringent culture medium containing enriched L-[ring-2H4]Tyr and isolated using a His6 tag. A comparison of these difference spectra revealed reproducible changes in bands that correspond to tyrosine and tyrosinate vibrational modes. A similar pattern of tyrosine/tyrosinate bands has also been observed in the bR --> M transition in bacteriorhodopsin, although the sign of the bands is reversed. In bacteriorhodopsin, these bands were assigned to Tyr-185, which along with Pro-186 in the F-helix, may form a hinge that facilitates alpha-helix movement.