Passive tumor targeting and imaging by using mercaptosuccinic acid-coated near-infrared quantum dots.

In this paper, we demonstrate the preparation of monodispersed quantum dots (QDs) as near-infrared (NIR) optical probes for in vivo pancreatic cancer targeting and imaging. The design of these luminescent probes involves functionalizing NIR QDs with ligand mercaptosuccinic acid (MSA), which targets the tumor site by enhanced permeability and retention effect. The colloidal and optical stability of the QDs can be maintained for >1 week. In vivo optical imaging studies in nude mice bearing pancreatic tumor show that the probes accumulate at tumor sites for >2.5 hours following intravenous injection of the functionalized NIR QDs. Tumor-labeling studies showed no evidence of harmful effects on the treated animals, even at a dose as high a ~50 mg/kg. These results demonstrate that the engineered MSA-functionalized QDs can serve as a diagnostic platform for early detection of cancer, as well as in image-guided precise surgical resection of tumors.

Oxidative stress in stroke pathophysiology validation of hydrogen peroxide metabolism as a pharmacological target to afford neuroprotection.

Reactive oxygen species (ROS) accumulation has been described in the brain following an ischemic insult. Superoxide anion is converted by superoxide dismutase into hydrogen peroxide (H2O2), and the latter is then transformed into the toxic hydroxyl radical, through the Haber-Weiss reaction, converted to water by glutathione peroxidase (GPx) or dismuted to water and oxygen through catalase. Accumulation of H2O2 has been suggested to exert neurotoxic effects, although recent in vitro studies have demonstrated either physiological or protective roles of this molecule in the brain. In particular, oxidative stress is critically involved in brain damage induced by transient cerebral ischemia. Here, we demonstrate that inhibition of GPx by systemic (i.p.) administration of mercaptosuccinate (MS, 1.5-150 mg/kg) dose-dependently reduces brain infarct damage produced by transient (2 h) middle cerebral artery occlusion (MCAo) in rat. Neuroprotection was observed when the drug was administered 15 min before the ischemic insult, whereas no effect was detected when the drug was injected 1h before MCAo or upon reperfusion. Furthermore, application of MS (1 mM) to corticostriatal slices limited the irreversible functional derangement of field potentials caused by a prolonged (12 min) oxygen-glucose deprivation. This effect was reverted by concomitant bath application of the catalase inhibitor 3-aminotriazole (20mM), suggesting the involvement of catalase in mediating the neuroprotective effects of MS. Thus, our findings demonstrate that MS is neuroprotective in both in vivo and in vitro ischemic conditions, through a mechanism which may involve increased endogenous levels of H2O2 and its consequent conversion to molecular oxygen by catalase.

Klinefelter's syndrome and rheumatoid arthritis. Report of a case and review of the literature.

Our case report describes a patient with Klinefelter's syndrome (KFS) associated with rheumatoid arthritis (RA). He had active RA in 1985 but his arthritis almost subsided in 1993 without intensive treatments for RA as well as KFS. Recently, the lower levels of testosterone in male RA patients, especially at the active phase has been reported. However, it is still questionable whether hypogonadism is a predisposing factor or just a consequence of disease. Since our case had a mild clinical course, and since the incidence of RA associated with KFS is very rare in comparison with other rheumatic diseases, may suggest that the low levels of testosterone are not a predisposing factor to the activity of RA.

Failure of oral thiomalate to act as an alternative to intramuscular gold in rheumatoid arthritis.

Ten patients with active rheumatoid arthritis (RA) were entered into a pilot study to evaluate the effectiveness of thiomalic acid as a disease modifying agent and to assess its toxicity. Oral thiomalic acid (100 mg) was given daily for up to six months. Changes in disease activity were recorded monthly and all side effects noted. No patient recorded any improvement in subjective well being, pain score, or duration of early morning stiffness. No significant change occurred in articular index or haemoglobin (Hb); the erythrocyte sedimentation rate (ESR) showed a tendency to increase. Only three patients completed six months' treatment; six withdrew because of toxic reactions (three with rashes and three with severe gastrointestinal upset) and one because of lack of effect. Thiomalic acid alone appears to have no significant antirheumatic activity and is associated with an unacceptably high incidence of adverse reactions.

Antibodies to Proteus in rheumatoid arthritis.

Increased levels of Proteus antibodies were found in patients with rheumatoid arthritis and coeliac disease, when compared to normal controls or patients with SLE and sarcoidosis.

Activity of known antischistosomal agents on early-developing forms of Schistosoma mansoni.

Sixteen compounds, including several series of antischistosomal agents, were tested in mice (subcutaneous, oral, and intramuscular routes), previously injected intraperitoneally with 175 plus or minus 25 Schistosoma mansoni cercariae. Most drugs were given in a 5-day regimen, first dose being administered 3 hr before cercarial inoculation. Ten days after infection the animals were killed, the schistosomules collected from peritoneal washings, and counted under a dissecting microscopy (free organisms and larvae surrounded by macrophages). A high degree of activity (abscess of free larvae) was observed with Hoechst S-616 and S668, Ciba 17,581, Oxamniquine (Pfizer), and RD 12,869 compounds. A significant reduction (P less than 0.05) in the number of larvae was observed with A-16,612, Sb-EDTA, Hycanthone, Schistomide, Trichlorphone, and Antiomaline. No activity on nearly developing forms of S. mansoni was observed after treatment with Mirasan, Hoechst S-201, Schistocide T-109, Lucanthone, and Wellcome 153C51. In conclusion, from 16 compounds taken at random, all of which are active on mature schistosome infections, 11 displayed prophylactic activity. This indicates a high sensitivity of the technique using peritoneal schistosomules.