13-cis-Retinoic acid therapy induces insulin resistance, regulates inflammatory parameters, and paradoxically increases serum adiponectin concentration.

13-cis-Retinoic acid treatment causes insulin resistance and disturbances in lipid and glucose metabolism. We studied how 13-cis-retinoic acid affects inflammatory factors and adiponectin. A total of 23 healthy patients (age, 24.9 +/- 0.9 years; body mass index, 22.6 +/- 0.7 kg/m(2)) who received 13-cis-retinoic acid treatment of acne participated in the study. The patients were studied before the treatment, after 3 months of therapy, and 1 month after the treatment. Inflammatory parameters were measured, and a 4-hour oral glucose tolerance test was performed at each visit. Treatment with 13-cis-retinoic acid resulted in a significantly elevated serum adiponectin concentration (from 24.9 +/- 2.5 to 29.4 +/- 3.6 mg/L, P < .05), hemoglobin A(1c) (from 5.27% +/- 0.05% to 5.42% +/- 0.06%, P < .01), C-peptide area under the curve (from 314.2 +/- 16.6 to 350.0 +/- 21.0 (nmol . min)/L, P < .05), and triglycerides (from 0.97 +/- 0.06 to 1.29 +/- 0.10 mmol/L, P < .05), whereas high-density lipoprotein cholesterol decreased (from 1.50 +/- 0.07 to 1.38 +/- 0.08 mmol/L, P < .05). The increase in adiponectin during 13-cis-retinoic acid therapy correlated with baseline triglycerides (r = 0.51, P < .02). Many inflammatory markers, which were nonsignificantly elevated during therapy, decreased significantly after cessation of treatment. These were C-reactive protein (median from 1.78 to 1.23 mg/L, P < .05), soluble intercellular adhesion molecule 1 (from 210 +/- 10 to 204 +/- 10 microg/L, P < .02), ceruloplasmin (256 +/- 17 to 231 +/- 17 microg/L, P < .02), and erythrocyte sedimentation rate (from 6.4 +/- 1.3 to 4.7 +/- 0.9 mm/h, P < .02). Interleukin 6 concentration was unaffected by the therapy, but decreased significantly after the treatment (from 2.18 +/- 0.46 to 1.65 +/- 0.43 ng/L, P < .05). In conclusion, although treatment with 13-cis-retinoic acid results in disturbances in glucose and lipid metabolism, paradoxically serum adiponectin concentration increases. 13-cis-Retinoic acid has profound effects on the regulation of inflammatory markers.

Distribution of radioiodinated estramustine binding protein antibody in mice with DU-145 prostate cancer xenograft.

BACKGROUND: Estramustine phosphate (EMP) and estramustine binding protein antibody (EMBP-AB) accumulate in the mouse prostate. The distribution of radioiodinated EMBP-AB in tumor mice was investigated to assess its therapeutic potential against prostate cancer. MATERIALS AND METHODS: Mice with DU-145 prostate cancer xenografts received 243 microCi of I-125-labeled EMBP-AB (RI-EMBP-AB). The concentration of activity in different organs was measured 4 h after the injection. RESULTS: The blood contained 0.45% of the injected dose per gram, the prostate 2.4%, the testes 0.95% and the tumor 0.65%. Radioactivity in these organs decreased more rapidly than in other organs. The doses of radiation absorbed by the prostate and the tumor, assuming a 1 mCi injected dose, were 1.81 and 0.92 cGy, respectively. CONCLUSION: Most other organs would receive relatively high doses of radioactivity, were I-125 to be used in therapeutic doses. Therefore, RI-EMBP-AB is not beneficial in radionuclide treatment as compared to possible EMP applications.

Radionuclide imaging of tumor xenografts in mice using a gelatinase-targeting peptide.

Tumors express MMP-2 and MMP-9 gelatinases, which are involved in the formation of tumor vasculature. This suggests that a tumor and its surrounding neovasculature can be visualized by a sensitive gelatinase recognition method. We have studied tumor radioimaging using a gelatinase inhibitory peptide CTTHWGFTLC (CTT), which in a mouse model targets the tumor site following an intravenous injection. We determined a solution NMR structure of CTT and its retro-inversion peptide, and prepared 125I and 99mTc-labelled CTT peptide derivatives. Radiolabelled CTT inhibited gelatinases in vitro, and homed to a tumor xenograft in mice. In normal mice, CTT was instead rapidly cleared from the circulation mainly through the kidney and, after 24 h, no significant radioactivity was accumulated in healthy tissues. Gamma camera imaging of a primary tumor in live mice was obtained with double-labelled liposomes, which were coated with 99mTc-CTT and encapsulated with 125I albumin. CTT also targeted liposomes to the lungs of tumor-bearing mice, which may indicate the existence of non-visible lung micrometastases. Our studies suggest that selective gelatinase-targeting compounds could be useful in the early detection and imaging of primary tumors and metastases.

Dental analgesia produced by non-painful low-frequency stimulation is not influenced by stress or reversed by naloxone.

The dental pain threshold elevation produced by non-painful, low-frequency transcutaneous electrical nerve stimulation (TENS) in healthy humans was not reduced by the administration of 0.8 mg of naloxone i.v. Neither ACTH, prolactin nor growth hormone (GH) release were related to the pain threshold elevations. The present study indicates that the dental pain threshold elevation during non-painful, low-frequency TENS is not based on the same opioid-dependent mechanisms as the dental pain threshold elevation during acupuncture or the clinical analgesia during low-frequency TENS. Stress or other adenohypophyseal mechanisms involving ACTH, prolactin or GH do not explain the analgesia induced by non-painful, low-frequency TENS.

Anti-alpha-fetoprotein imaging is useful for staging hepatoblastoma.

BACKGROUND: Liver transplantation (Tx) has become an alternative treatment of malignant childhood liver tumors, and the importance of careful pretransplantation evaluation has been emphasized. Anti-alpha-fetoprotein (AFP) imaging has been suggested for evaluation of adult patients with AFP-positive tumors. METHODS: Antibody imaging utilizing Tc-99 m-labeled monoclonal anti-AFP Fab' fragments was used to demonstrate pathologic uptake in hepatoblastoma (HB). RESULTS: Radical operation or liver Tx was not possible after four cycles of chemotherapy in a child with HB because of a single extrahepatic metastasis. Chemotherapy was continued, and reevaluation with anti-AFP imaging demonstrated a pathologic uptake only in the liver. Subsequently, a right liver lobe resection was performed. Along with a new rise in serum AFP, repeated anti-AFP imaging revealed active liver tumor but no metastases. A liver Tx was performed, and the child is well with a normal serum AFP level 18 months after the operation. CONCLUSION: This is the first case of pediatric HB in which anti-AFP imaging has been successfully used for patient management.

A prospective study of inflammation markers in patients at risk of indirect acute lung injury.

Systemic inflammation triggered by insults like sepsis and acute pancreatitis may play a role in development of indirect acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Because little is known about the course of systemic inflammation on the days preceding diagnosis of ARDS, we prospectively monitored immune inflammatory status in 52 patients at risk and we assessed the presence of ALI and ARDS on day 7 after admission to the intensive care unit. On admission, serum interleukin (IL) 8, IL-6, and soluble IL-2 receptor concentrations were significantly higher in patients with subsequent ALI (n = 18) than in patients without ALI (n = 30). During a 4-day follow-up, IL-8 and IL-6 levels of ALI patients remained high and those of non-ALI patients decreased. None of the markers discriminated ARDS patients (n = 9) from non-ARDS ALI patients (n = 9). Among 11 patients with acute pancreatitis, ALI patients had significantly higher IL-8, IL-6, and phagocyte CD11b expression levels than did non-ALI patients, whereas among 14 patients with massive transfusion, respective findings in ALI and non-ALI patients were comparable. Results give credence to the view that systemic inflammation plays a role in development of ALI triggered by pancreatitis, but not in that by massive transfusion. This finding, if confirmed in studies with sufficient statistical power, suggests that the patients with massive transfusion do not necessarily benefit from novel biotherapies aimed at altering the course of systemic inflammation.

In vivo effects of bisphenol A on the polecat (mustela putorius).

Bisphenol A (BPA), an environmental estrogen derived from the plastic industry, was given orally via incorporation into the food of 30 male and female polecats at 3 different doses (10, 50, or 250 mg/kg body weight/day) for 2 wk with 10 animals acting as controls. Several hormone levels in the plasma were determined as well as the activities of the phase I and II biotransformation enzymes 7-ethoxyresorufin O-deethylase (EROD), cytosolic glutathione S-transferase (GST), and UDP-glucuronosyltransferase (UDPGT). BPA did not cause any macroscopic effects on body mass or the health of the animals. UDPGT and GST activities increased significantly in direct correlation with increasing BPA exposure in females and UDPGT increased in a dose-related manner in males. There was no change in the plasma T4 and testosterone concentrations of the males with increasing BPA exposure. Discriminant analysis indicated that the group receiving 10 mg BPA/kg body weight/d was not different from the control group but the groups receiving 50 and 250 mg/kg body weight/d were different from the control group. This suggests physiological changes in the groups receiving 50 or 250 mg BPA/kg body weight/d.