Central and peripheral changes in catecholamine-synthesizing enzyme activities after systemic administration of the neurotoxin DSP-4

In brain regions containing noradrenergic (NA) cell bodies or terminals, DSP-4 induces changes in the activity of catecholamine-synthesizing enzymes which suggest that central NA neurons are lesioned by this neurotoxin. In contrast, the lack of change in the same enzymatic activities in an area containing mostly adrenergic (A) neurons (C2 region), favors the hypothesis of a resistance of the A neurons to DSP-4. Furthermore, the enzymatic changes observed in peripheral organs suggest a peripheral activation of the NA cell bodies in response to lesioning of the sympathetic terminals by DSP-4.     

Aging pathways for organophosphate-inhibited human butyrylcholinesterase, including novel pathways for isomalathion, resolved by mass spectrometry.

Some organophosphorus compounds are toxic because they inhibit acetylcholinesterase (AChE) by phosphylation of the active site serine, forming a stable conjugate: Ser-O-P(O)-(Y)-(XR) (where X can be O, N, or S and Y can be methyl, OR, or SR). The inhibited enzyme can undergo an aging process, during which the X-R moiety is dealkylated by breaking either the P-X or the X-R bond depending on the specific compound, leading to a nonreactivatable enzyme. Aging mechanisms have been studied primarily using AChE. However, some recent studies have indicated that organophosphate-inhibited butyrylcholinesterase (BChE) may age through an alternative pathway. Our work utilized matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry to study the aging mechanism of human BChE inhibited by dichlorvos, echothiophate, diisopropylfluorophosphate (DFP), isomalathion, soman, sarin, cyclohexyl sarin, VX, and VR. Inhibited BChE was aged in the presence of H2O18 to allow incorporation of (18)O, if cleavage was at the P-X bond. Tryptic-peptide organophosphate conjugates were identified through peptide mass mapping. Our results showed no aging of VX- and VR-treated BChE at 25 degrees C, pH 7.0. However, BChE inhibited by dichlorvos, echothiophate, DFP, soman, sarin, and cyclohexyl sarin aged exclusively through O-C bond cleavage, i.e., the classical X-R scission pathway. In contrast, isomalathion aged through both X-R and P-X pathways; the main aged product resulted from P-S bond cleavage and a minor product resulted from O-C and/or S-C bond cleavage.     

Contribution of hypoxia-measuring molecular imaging techniques to radiotherapy planning and treatment

Hypoxia is related to poor prognosis because it is associated to chemo-and radioresistance. During recent years the evolution of imaging methods like PET/CT and MRI has meant the appearance of new perspectives with direct implications in radiation therapy. We discuss previous experiences in staging, planning and in the follow-up process with these techniques for measuring tumour hypoxia.     

Coccygectomy has a favorable effect on the intensity, manifestation, and characteristics of pain caused by coccygodynia: a retrospective evaluation of 34 patients followed for 3–18 years

Background  Coccygodynia can cause severe pain and disability in patients. There are contradictions in the literature regarding the final results of coccygectomy for coccygodynia. We evaluated the long-term effects of coccygectomy on the intensity, characteristics, and manifestation of pain caused by coccygodynia to determine the adequacy of operation among treatment modalities. Materials and methods  Thirty-four patients with coccygodynia were treated by coccygectomy. In 22 cases, trauma, and in one case childbirth was the cause. 11 cases were regarded as idiopathic. The intensity, characteristics of pain, and the most painful activities were evaluated at an average of 7.6 (3–18) years of follow-up time. Results  Before the operation, all 34 patients had pain while sitting, moreover, 26 of them had pain during standing, walking, at night or a combination of these. 21 patients had intolerable or very intensive, mainly acute, sharp or burning pain. 11 patients had dyschesia, 2 had dysuria and 6 had dyspareunia. At follow-up, 7 patients were completely free of pain, 15 others had moderate, 11 medium, and only one patient had severe, but none had intolerable pain. Only seven patients had acute, sharp or burning pain postoperatively. The decrease of average pain score from 8.0 to 3.2 was significant (P < 10⁻¹²). The number of the patients with dyschesia and dyspareunia decreased from 11 to 7 and from 6 to 3, respectively. Two patients had dysuria, but their complaints did not change after the operation. One of the two patients who needed reoperation had an excellent final result, while the other remained unchanged. 12 and 16 patients (together 82%) regarded the final result of the operation excellent and good, respectively. The condition of five others did not change, while one became worse. The patients with younger age, smaller body mass index, and less co-morbidities had better final result. There were no serious complications. Conclusion  Coccygectomy for coccygodynia is a safe method to decrease the intensity of pain and other complaints of the patients. The operation can be the choice of treatment if conservative measures fail.