Pharmacokinetics of aditoprim and trimethoprim in buffalo calves

Pharmacokinetic parameters of two antifolates, trimethoprim and aditoprim, were studied in buffalo calves. The elimination half-life of aditoprim (6.14 h) was nearly twice as long as that of trimethoprim (3.08 h) and compares well with values observed in heifers. This longer half-life of aditoprim is a result of its much larger distribution volume (four to five times larger) because the clearance of aditoprim was about twice as high as that of trimethoprim. The longer half-life of aditoprim is expected to give a longer duration of in vivo bacteriostatic activity than that of trimethoprim.     

Clinical experience with alpha-particle emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6.

alpha-Particle-emitting radionuclides, such as (211)At, with a 7.2-h half-life, may be optimally suited for the molecularly targeted radiotherapy of strategically sensitive tumor sites, such as those in the central nervous system. Because of the much shorter range and more potent cytotoxicity of alpha-particles than of beta-particles, (211)At-labeled agents may be ideal for the eradication of tumor cells remaining after surgical debulking of malignant brain tumors. The main goal of this study was to investigate the feasibility and safety of this approach in patients with recurrent malignant brain tumors. METHODS: Chimeric antitenascin monoclonal antibody 81C6 (ch81C6) (10 mg) was labeled with 71-347 MBq of (211)At by use of N-succinimidyl 3-[(211)At]astatobenzoate. Eighteen patients were treated with (211)At-labeled ch81C6 ((211)At-ch81C6) administered into a surgically created resection cavity (SCRC) and then with salvage chemotherapy. Serial gamma-camera imaging and blood sampling over 24 h were performed. RESULTS: A total of 96.7% +/- 3.6% (mean +/- SD) of (211)At decays occurred in the SCRC, and the mean blood-pool percentage injected dose was < or = 0.3. No patient experienced dose-limiting toxicity, and the maximum tolerated dose was not identified. Six patients experienced grade 2 neurotoxicity within 6 wk of (211)At-ch81C6 administration; this neurotoxicity resolved fully in all but 1 patient. No toxicities of grade 3 or higher were attributable to the treatment. No patient required repeat surgery for radionecrosis. The median survival times for all patients, those with glioblastoma multiforme, and those with anaplastic astrocytoma or oligodendroglioma were 54, 52, and 116 wk, respectively. CONCLUSION: This study provides proof of concept for regional targeted radiotherapy with (211)At-labeled molecules in oncology. Specifically, the regional administration of (211)At-ch81C6 is feasible, safe, and associated with a promising antitumor benefit in patients with malignant central nervous system tumors.     

Nitric oxide synthase inhibitor,nitro-iminoethyl-L-ornithine,reduces ischemia-reperfusion injury in rabbit skeletal muscle

Nitric oxide (NO), originally identified as the mediator of endothelial-dependent relaxation of vascular smooth muscle, is now known to also have cytotoxic effects under certain conditions. Thus, we have investigated the effects of inhibition of NO synthesis on ischemia/reperfusion injury in the rabbit rectus femoris muscle. Three and a half hours of ischemia and 24 hours of reperfusion resulted in a 56% loss of viability. In muscles receiving an infusion of the nitric oxide synthase inhibitor, L-NIO (30 μM), the loss of viability was reduced to 15%. Post-ischemic blood flow was increased in muscles receiving a saline infusion, whereas there was a marked decrease in blood flow for at least the first 60 minutes of reperfusion in muscles treated with L-NIO (30 μM). The increase in myeloperoxidase levels (indicative of neutrophil accumulation) following 24 hours of reperfusion was attenuated with L-NIO infusion by approximately 50% and the reperfusion-induced edema was also attenuated in L-NIO treated muscle. These findings suggest that endogenous NO production during ischemia/reperfusion injury may be deleterious to muscle survival. © 1994 Wiley-Liss, Inc.     

Coronary reperfusion with a new catheter in six patients with acute occlusion after angioplasty

A new catheter was used in an attempt to re-establish coronary flow in six patients with acute occlusion after angioplasty and prior to emergency coronary artery bypass surgery. All patients suffered from severe chest pain, and the electrocardiogram showed signs of acute transmural ischemia. A reperfusion catheter manufactured by Advanced Cardiovascular Systems (ACS) has 36 side holes spirally arranged along the distal 10 cm. It is introduced over an exchange wire. After the catheter was positioned across the occlusion, five patients had complete relief of chest pain, and another patient had partial relief. The electrocardiogram normalized in all six patients (in one only initially). Two patients developed a limited myocardial infarction, but four did not. The time between introduction of the reperfusion catheter and aorta cross clamping varied between 1.5 and 6.5 hours, and there were no complications related to its use. We conclude that the ACS reperfusion catheter is useful in re-establishing coronary blood flow after failed angioplasty and prior to emergency coronary artery bypass surgery.     

Morphological study of some hypothalamic centers in rats after deafferentation of the mediobasal hypothalamus

The volume of the nuclei and nucleoli of certain hypothalamic centers (SON, PVN, SCN, AN, VMN) was determined in control rats and in rats after deafferentation of the mediobasal hypothalamus. Sex differences were found in the parvocellular formations of the control animals: The volumes of nuclei and nucleoli of neurons of AN and VMN, and also of the nucleolus of SCN neurons were larger in females than in males. After deafferentation of the mediobasal hypothalamus the volume of the cell nuclei was increased, especially in hypothalamic formations located outside the isolated zone. This increase was more clearly defined in rats constantly in a state of estrus after the operation. Statistically significant differences between volumes of both nuclei and nucleoli of the cells in subgroups of rats with permanent estrus and with permanent diestrus were found only in the case of SCN. No such differences were found for AN, despite the considerable difference in the constant of luteinizing hormone in the pituitary of the same rats. It is suggested that gonadotropin releasing factors are not produced by the cells of AN and that control over the succession of phases of the sex cycle may be exerted by SCN.Laboratory of Neuroendocrinology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 352–354, March, 1980.     

E-selectin S128R polymorphism and severe coronary artery disease in Arabs

Background  

The E-selectin p. S128R (g. A561C) polymorphism has been associated with the presence of angiographic coronary artery disease (CAD) in some populations, but no data is currently available on its association with CAD in Arabs.     

Ontogeny of the VIP system in the gastro-intestinal tract of the Axolotl,Ambystoma mexicanum: successive appearance of co-existing PACAP and NOS

Evidence for the presence and potential co-existence of vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP) and nitric oxide synthase (NOS) in gastro-intestinal endocrine cells and/or nerve fibers is conflicting and very few results exist on development. This immunofluorescence study aims to clarify the appearance and localization of VIP, PACAP and NOS in the gastro-intestinal tract of the Axolotl, Ambystoma mexicanum, during ontogeny. VIP-immunoreactivity appeared in nerve fibers as early as on day 3 after hatching likely indicating a particular role, such as a trophic action, of VIP in very early development. PACAP-immunoreactivity was observed 3 days later within the VIP-immunoreactive (-IR) fibers. From this time on, VIP- and PACAP-immunoreactivity exhibited complete co-existence. VIP/PACAP-IR fibers were found throughout the gastro-intestinal tract. They were most prominent in the myenteric plexus and the muscle layers and less frequent in the submucosa. NOS-immunoreactivity appeared as late as at the 1st (64 days) juvenile stage in a subpopulation of the VIP/PACAP-IR fibers that contacted submucosal arteries. We found only very few VIP/PACAP-IR perikarya, indicating that part of the VIP/PACAP-IR fibers is of extrinsic origin. On day 12 and in the 1st and 2nd (104 days) juvenile stage, infrequent PACAP-IR entero-endocrine cells were noted, while neither VIP- nor NOS-immunoreactivity occurred in endocrine cells at any stage of development. The complete coexistence of neuronal PACAP- and VIP-immunoreactivities and their very early appearance in ontogeny may suggest important and coordinated roles of both peptides in the control of Axolotl gastro-intestinal activity, while the VIP/ PACAP/NOS-IR fibers may be involved in the regulation of submucosal blood flow.     

Using psychometric ability to improve education in ultrasound-guided regional anaesthesia: a multicentre randomised controlled trial

The learning curve for novices developing regional anaesthesia skills, such as real-time ultrasound-guided needle manipulation, may be affected by innate visuospatial ability, as this influences spatial cognition and motor co-ordination. We conducted a multinational randomised controlled trial to test if novices with low visuospatial ability would perform better at an ultrasound-guided needling task with deliberate practice training than with discovery learning. Visuospatial ability was evaluated using the mental rotations test-A. We recruited 140 medical students and randomly allocated them into low-ability control (discovery learning), low-ability intervention (received deliberate practice), high-ability control, and high-ability intervention groups. Primary outcome was the time taken to complete the needling task, and there was no significant difference between groups: median (IQR [range]) low-ability control 125 s (69–237 [43–600 s]); low-ability intervention 163 s (116–276 [44–600 s]); high-ability control 130 s (80–210 [41–384 s]); and high-ability intervention 177 s (113–285 [43–547 s]), p = 0.06. No difference was found using the global rating scale: mean (95%CI) low-ability control 53% (95%CI 46–60%); low-ability intervention 61% (95%CI 53–68%); high-ability control 63% (95%CI 56–70%); and high-ability intervention 66% (95%CI 60–72%), p = 0.05. For overall procedure pass/fail, the low-ability control group pass rate of 42% (14/33) was significantly less than the other three groups: low-ability intervention 69% (25/36); high-ability control 68% (25/37); and high-ability intervention 85% (29/34) p = 0.003. Further research is required to determine the role of visuospatial ability screening in training for ultrasound-guided needle skills.