Treatment of schizophrenic psychoses with Lyorodin

Forty-four patients suffering from acute and chronic schizophrenic psychoses were used to obtain, by using Lorr's scale (IMPS) and taking the changes in disease state observed within three months as a base, suggestions or pointers as to the proper treatment of disease with fluphenazine (lyorodin) which is a neuroleptically highly potent phenothiazine derivative. Megalomania, grandiose delusions apathetic and depressive syndromes showed marked tendencies toward major improvement. An "antiautistic" effect was observed in chronic patients. The effective dose was between 6 and 12 mg a day. The drug was well tolerated. In the majority of cases it was also necessary for antiparkinsonian drugs to be administered to patients. After twelve months of treatment, slight to major improvements or even freedom from symptoms could be observed in 28 cases (or 64%).     

Metabolic mapping of the effects of oral alcohol self-administration in rats

A method for the quantitation of protein carbonyls, which have been widely employed as markers of protein oxidative damage, is described. Protein carbonyls were derivatized with tritiated sodium borohydride and the tritiated proteins were separated on SDS-PAGE. Protein bands, visualized by Coomassie blue staining, were then excised and incubated in 30% H2O2 at 60 degrees C for 48 h. Tritium, incorporated into the proteins, was quantitated by liquid scintillation counting after gel solubilization by H2O2. This method can be applied to the measurement of carbonylation of specific proteins as it employs SDS-PAGE and has the advantage that unreacted NaB3H4 in the labeling reaction mixture need not be removed. The present method, when combined with immunochemical detection of protein carbonyls, should be very useful in the quantitation of oxidative damage to individual proteins.     

Aspirin-triggered 15-epi-lipoxin A4 (ATL) generation by human leukocytes and murine peritonitis exudates: development of a specific 15-epi-LXA4 ELISA

Aspirin (ASA) triggers the formation of 15-epi-lipoxins (15-epi-LXs or ATL [ASA-triggered LX]), which are potent bioactive eicosanoids that may contribute to the therapeutic impact of ASA. To elucidate the role of these new compounds in vivo, it is essential to establish quick and sensitive detection methods. To this end, we prepared an enzyme-linked immunosorbent assay specific for 15-epi-LXA4 that proved to be highly sensitive (IC50 approximately 50 pg, minimum detection approximately 3.5 pg) and stereoselective. The amounts of 15-epi-LXA4 generated by human neutrophils from peripheral blood of healthy volunteers using this enzyme-linked immunosorbent assay were in agreement with those values obtained by liquid chromatography. Formation of 15-epi-LXA4 was cell ratio-dependent during THP-1 (a monocytic leukemia cell line)-neutrophil interactions with ASA-treated cells, and 15-epi-LXA4 was not detected with either cell type alone. Generation of 15-epi-LXA4 was also examined in murine peritonitis with ASA administration. Exudates from ASA-treated mice showed increased production of 15-epi-LXA4 that was diminished by indomethacin, a blocker of ASA-dependent acetylation of prostaglandin G/H synthase. A cytochrome P450 inhibitor administered in the presence of ASA did not prevent 15-epi-LXA4 formation, which suggests that P450 does not significantly contribute to formation of 15-epi-LXA4 in this murine model. These results indicate that the new enzyme-linked immunosorbent assay is both sensitive and selective for 15-epi-LXA4 and that 15-epi-LXA4 is produced by human leukocyte-leukocyte interactions. In addition, 15-epi-LXA4 is generated by inflammatory exudates when ASA is administered during murine peritonitis and when prostaglandin G/H synthase is upregulated and acetylated. This assay should provide rapid means to investigate 15-epi-LXA4 generation in both cellular and animal models.     

The antitumour activity of the prodrug N-L-leucyl-doxorubicin and its parent compound doxorubicin in human tumour xenografts

The antitumour activity of the investigational agent N-L-leucyl-doxorubicin (Leu-DOX) was compared with that of doxorubicin (DOX) in human tumour xenografts growing subcutaneously in athymic nude mice. Leu-DOX was developed as a prodrug of DOX, and may be converted into the clinically active parent compound by hydrolytic enzymes present in or on tumour cells. It has been suggested that a better therapeutic index with a reduced cardiac toxicity and higher efficacy might be obtained. Both compounds were administered intravenously weekly for 2 weeks, each at maximum tolerated doses of 8 mg/kg and 28 mg/kg for DOX and Leu-DOX, respectively. The panel of xenografts represented three different tumour types. Leu-DOX showed antitumour activity, defined as tumour growth inhibition > 50% and specific growth delay > 1.0, in 10 of the 16 tumours, including two of five breast, five of seven small cell and three of four non-small cell lung carcinomas. In comparison, DOX was active in one breast, four small cell lung and two lung adenocarcinoma xenografts. In all the DOX sensitive lung tumours, Leu-DOX showed higher efficacy than the parent compound. Based on the results of the present study, and since phase I clinical trials with Leu-DOX have already been performed, phase II clinical evaluation of Leu-DOX in patients with breast and lung cancer is recommended.     

Arthroscopic-assisted reduction of distal radius fractures

The outcomes of seven patients with severe comminuted intraarticular fractures of the distal radius treated by arthroscopic reduction and percutaneous external fixation (ARPEF) were retrospectively reviewed. All of the fractures were classified as C3 types using the AO classification scheme. Outcomes were evaluated using the Gartland and Werley functional criteria, an objective wrist examination, a radiographic analysis, and a self-assessment outcome form at an average follow-up of 27 months (range, 12 to 45 months). All patients were free of pain and had returned to their prior occupations. No patient had articular incongruency of greater than 1 mm, and there was no evidence of radiocarpal degenerative change. Active range of motion and maximal grip strength averaged 92% and 98%, respectively, of the uninjured wrist. The technique of arthroscope-assisted reduction and percutaneous external fixation yielded excellent results in a small group of patients, with minimal complications.     

Time-dependent differential changes of immune function in rats exposed to chronic intermittent noise

Noise is a highly relevant environmental and clinical stressor. Compared to most other experimental stressors, noise is a modest activator of neuroendocrine pathways that mimic the situation in human health where neuroendocrine activation by environmental stressors is often absent or difficult to establish. Little is known about the effects of noise exposure on the immune system. In the present work, the effects of a low-intensity chronic intermittent unpredictable noise regimen on various parameters of immune function was studied. Male wistar rats were exposed to a randomized noise protocol (white noise, 85 dB, 2-20 kHz) for 10 h per day, 15 min per h over a total period of 3 weeks. Control animals were exposed to ambient sound only. Immune function was monitored after 24 h, 7 days, and 21 days of noise exposure. Noise induced several significant changes in immune function in a time-dependent differential pattern involving both immunosuppression and immunoenhancement. After 24 h, serum IgM levels were increased and peripheral phagocytic activity was decreased. Splenic lymphocytic proliferation to mitogens was significantly decreased after 7 days, but slightly elevated after 3 weeks. The activity of splenic NK cells was increased significantly after 24 h and 7 days, but suppressed after 3 weeks. These results show that various parameters of immune function are affected differentially over time in a period of chronic mild noise stress, possibly due to sequential activation of different physiological mechanisms.