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1.
Despite the use of gold complexes in modern medicine for over 100 years and the use of gold complexes in the management of
rheumatoid disease for more than 60 years, the definitive mechanisms of action for efficacy and for toxicity have not been
established.
Gold is a group 1b metal in the periodic table with several oxidation states but it is only Au(I) which is active in the biological
milieu. Gold sodium thiomalate is not only a polymeric structure, but also has the chiral ligand, thiomalic acid. Gold sodium
thiomalate thus can exist in several different physical states which may have different biological activity. In addition the
pharmacokinetic profile of gold complexes has been of little value in the understanding of either the mechanism of action,
efficacy or toxicity for both the injectable and the oral gold complexes. Many authors have misinterpreted research data on
the activities of gold complexes because they compared gold complexes of different structures, and gold complexes which exist
at different pH.
Experimental work in our laboratory has identified that gold sodium thiomalate is a mixture and can exist as either a yellow
or a colourless solution. These have some similar but several different biological activities.
Many factors contribute to the lack of understanding of the action of gold complexes. Some of these factors are related to
the wide variation in physical structure and biological activities exhibited by these compounds. 相似文献
2.
This paper describes studies aimed at determining the acute anticholinergic and delayed neurotoxic potential of the organophosphate insecticide pirimiphos-methyl (O-2-diethylamino-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate) in the hen. Delayed neuropathy was assessed by biochemical measurement of neuropathy target esterase (NTE) activities in the brain and spinal cord, clinical signs of neuropathy over two 21-day periods and histological assessment of nervous tissue. Acetylcholinesterase (AChE) activity was also determined in the brain and spinal cord. Hens were given a single oral dose of 100 mg kg-1 pirimiphos-methyl, which was followed by a repeated dose after 21 days. Tri-o-cresyl phosphate (TOCP), 500 mg kg-1, was used as a positive control. All pirimiphos-methyl-treated hens received prophylactic doses of N-methylpyridinium-2-aldoxime methanesulphonate (P2S) and atropine sulphate. Hens dosed with pirimiphos-methyl had very low AChE activities (less than 20% of control) in both the brain and spinal cord, 24 and 48 h after dosing. In the TOCP-treated hens, the activities were about 90% of control. NTE activities in the brain and spinal cord of pirimiphos-methyl-treated hens were identical to those in the controls, while they were profoundly inhibited (greater than 80%) in the TOCP-treated hens. All hens dosed with pirimiphos-methyl showed the expected signs of AChE inhibition and, following recovery, usually by Day 5, no clinical signs of delayed neuropathy were seen. The TOCP-treated hens developed clinical signs of neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
3.
We report a case of aneurysmal bone cyst (ABC) of the terminal phalanx of the thumb in a young boy, which was treated successfully with complete curettage with preservation of the growth plate. Three years later he was asymptomatic, with normal growth of the thumb, full range of movement and no evidence of recurrence. For this rare benign cyst in a child's hand, we recommend simple surgery to preserve the growth plate. 相似文献
4.
Preliminary evidence for a role of apolipoprotein E alleles in identifying haemodialysis patients at high vascular risk 总被引:1,自引:0,他引:1
Olmer M; Renucci JE; Planells R; Bouchouareb D; Purgus R 《Nephrology, dialysis, transplantation》1997,12(4):691-693
Conventional risk factors have very low predictive power in identifying
haemodialysis patients at high risk of vascular accidents. A role for
apolipoprotein E isotypes was looked for in a small, but rigorously
defined, cohort of longterm haemodialysis patients. In individuals with
high vascular risk, as identified by higher common carotid intima/media
thickness, we found an excess of apolipoprotein E4 alleles. This
preliminary result requires confirmation in large patient cohorts.
相似文献
5.
6.
7.
M D Stonard P G Phillips J R Foster M G Simpson E A Lock 《Clinica chimica acta; international journal of clinical chemistry》1986,160(2):197-203
The concentration of renal alpha 2U-globulin increased in a dose-dependent manner in adult male but not female rats which received a single dose of 2,2,4-trimethylpentane (TMP). After administration of a single dose of 12 mmol TMP/kg to adult male rats, the renal concentration of alpha 2U-globulin reached a peak at 48 hours and returned to near background level after 7 days. These changes in renal alpha 2U-globulin concentration were closely paralleled by changes in renal hyaline droplet formation. Renal alpha 2U-globulin and hyaline droplets were absent in normal pre-puberty male rats, and neither could be stimulated by a single dose of TMP. alpha 2U-Globulin was localised in the renal cortex of adult male rats, in particular the S2 segment of the proximal tubule. A greater staining intensity due to alpha 2U-globulin was seen in the S2 and adjacent segments after a single dose of TMP. A strong association is suggested between the presence of renal hyaline droplets and the occurrence of alpha 2U-globulin. 相似文献
8.
9.
H. B. Jones C. R. Jenkins A. L. Bowdler M. G. Simpson E. A. Lock 《Acta neuropathologica》1997,93(3):241-251
The objectives of the studies described were to assess the ultrastructural neuropathology, blood-brain barrier (BBB) integrity
and calcium status of the cerebellum of rats following a single dose of 750 mg · kg–1
l-2-chloropropionic acid (l-2-CPA). The first indications of intoxication appeared at 36 h when condensation of many granule cells associated with Purkinje
cell degeneration and marked astroglial swelling were observed. Some electron-lucent granule cells were also noted lying amongst
these condensed forms. Condensed granule cells had swollen, electron-lucent mitochondria, dilated Golgi apparatus and nuclear
crenation. Occasionally, areas of granule cell necrosis were also present at this time. Granule cell condensation probably
represents a preliminary and irreversible stage in an excitotoxic process that leads to necrosis. At 48 and 72 h, most granule
cells were necrotic, and occasionally, extravasation of both erythrocytes and leucocytes into the expanded extravascular space
was observed. Evaluation of the BBB by ultrastructural cytochemical visualisation of horseradish peroxidase injected i.v.
2 min before killing by perfusion fixation showed substantial leakage. At 36 h post-dose, ultrastructural calcium localisation
using oxalate/pyroantimonate precipitation demonstrated a substantial increase in calcium pyroantimonate precipitate in mitochondria
and other membranous cytoplasmic organelles (especially the Golgi apparatus) in condensed granule cells, but with little in
their nuclei. However, their immediate neighbours (of ostensibly normal ultrastructural appearances) contained greater amounts
of intranuclear precipitate. Swollen astroglial cells (especially the Bergmann glia) contained considerable quantities of
precipitate. A possible excitotoxic mechanism via l-2-CPA-induced NMDA receptor agonism leading to overwhelming calcium influx and disruption of cellular calcium homeostasis
is proposed.
Received: 8 May 1996 / Revised: 1 September 1996 / Accepted: 11 September 1996 相似文献
10.
Endovascular stent implantation in patients with stenotic aortoarteriopathies: early and medium-term results. 总被引:1,自引:0,他引:1
Ernest S Siwik Stanton B Perry James E Lock 《Catheterization and cardiovascular interventions》2003,59(3):380-386
Data regarding stent implantation for stenotic aortoarteriopathy (SAA) are incomplete. We report on nine patients with this rare syndrome who underwent arterial stent implantation. Indications, results, and complications for patients with SAA were reviewed. Nine patients underwent 11 procedures. Twenty-two stents were implanted in the aorta or brachiocephalic vessels. Five patients had diffuse stenoses, three patients had middle aortic syndrome, and one patient had thoracic and abdominal coarctation. Associated diagnoses included Williams syndrome (2), neurofibromatosis (2), Takayasu's (1), and congenital rubella (1). Median gradient was 60 mm Hg (20-140 mm Hg). Poststent gradient was 15 mm Hg (0-60 mm Hg; P < 0.001). Additional stents were implanted in two patients and five underwent stent redilation. Two patients (22%) were found to have aneurysm formation. Stent implantation effectively provides gradient relief in SAA. Gradient reduction persists or is amenable to redilation. Importantly, however, uncomplicated stent implantation does not preclude aneurysm formation and may be more common than in traditional patient groups. 相似文献