Monoclonal anti-idiotypic antibody to a potent thromboxane A2 receptor antagonist and its interaction with thromboxane A2 receptor

A monoclonal anti-idiotypic antibody that interacts with thromboxane A2 receptor was generated using an anti-idiotypic approach. Idiotypic antibodies against a potent receptor antagonist, HS-145, were generated in rabbit. The idiotypic antibodies were then selected by an affinity procedure using SQ29,548-Affi-Gel-102 matrix. The selected idiotypic antibodies were used as surrogate receptor for anti-idiotypic antibody generation. A mouse monoclonal antibody, 3D-9E-12, was generated. It was shown to displace 125I-HS-145 from affinity-purified idiotypic antibodies. It also inhibits 125I-IS-145 binding to thromboxane A2 receptor in human platelet membranes in a dose-dependent manner. Furthermore, it attenuated U46,619-induced increase in [35S]guanosine 5'-O-(thiotriphosphate) binding and GTPase activity in human platelet membranes. Finally, it inhibited U46,619- but not PAF-induced platelet aggregation. These results indicate that 3D-9E-12 acts as a specific antagonist in the thromboxane A2 receptor.     

Acute renal failure complicating non-fulminant hepatitis A

Leucocyte cytoplasm is changed during long-term influence of bile in inflammation of gastric mucose. The symptom of gastric neutrophil yellow-cytoplasm has been analysed in 30-patient group after operation because of gastric peptic ulcer. The clinical usefulness is suggested in differential diagnosis of gastritis.     

Acute renal failure complicating nonfulminant hepatitis A

PURPOSE: To compare the orbital blood flow velocities of patients with long-standing ocular hypertension and patients with primary open-angle glaucoma. METHODS: Twenty patients with ocular hypertension were recruited from our clinic and underwent color Doppler imaging evaluation of their retrobulbar vessels. The blood flow velocities and resistance index of their central retinal artery, temporal short posterior ciliary artery, and ophthalmic artery were compared with those of 20 glaucoma patients individually matched for age and level of the highest untreated intraocular pressure ever recorded. RESULTS: Glaucoma patients had significantly lower peak systolic velocity and end-diastolic velocity than did patients with ocular hypertension in their central retinal artery (p < 0.001). No significant difference between the groups was observed in the other vessels studied. CONCLUSIONS: Glaucoma patients had lower blood flow velocity in the central retinal artery compared with that of ocular hypertension patients of similar age and level of untreated intraocular pressure. This might be important in the development of glaucomatous damage in those patients.     

Effects of cysteinyl-leukotriene receptor antagonist, thromboxane A2 receptor antagonist, and thromboxane A2 synthetase inhibitor on antigen-induced bronchoconstriction in patients with asthma

BACKGROUND: Leukotriene (LT) and thromboxane A2 (TXA2) receptor antagonists have been used in the treatment of asthma. OBJECTIVES: We examined the effects of an LT receptor antagonist, TXA2 receptor antagonist, and TXA2 synthetase inhibitor on bronchoprovocation test (BPT) in patients with mild-to-moderate atopic asthma. METHODS: BPT was performed four times in each of six asthmatics. Development of the immediate asthmatic reaction (IAR) and late asthmatic reaction (LAR) was confirmed on the first BPT (BPT1). After a 7-day washout period, an LT receptor antagonist (pranlukast, 450 mg/d), TXA2 receptor antagonist (seratrodast, 80 mg/d), or TXA2 synthetase inhibitor (ozagrel, 800 mg/d) was administered orally over 7 days at random using a cross-over method (BPT2-4). Blood levels of LTB4, LTC4, LTD4, 11-dehydrothromboxane B2, eosinophil cationic protein, and histamine were measured at reaction phases of pre-BPT, IAR, and LAR. RESULTS: Administration of pranlukast suppressed IAR by 80.5% (p < 0.0001) and LAR by 54.6% (p = 0.0391). Ozagrel significantly suppressed IAR by 39.5% (p = 0.0413), but the fall in FEV1 was >20% (21.56+/-4.173%). Seratrodast did not suppress IAR or LAR. Blood levels of chemical mediators did not correlate with the suppressive effects of the tested drugs. CONCLUSIONS: The LT receptor antagonist was considered to be the most effective. LT might play a more important role in the pathogenesis of asthma than TXA2. Our data showed that measurement of blood levels of chemical mediators is not useful in identifying the pathogenic mechanisms of asthma.     

On the formation and effects of thromboxane A2 in human platelets

Incubation of arachidonic acid and prostaglandin G2 with a suspension of human platelets led to formation of an unstable (t1/2, 41+/-7 s) compound, thromboxane A2. Thromboxane A2 induced irreversible aggregation of washed platelets and of platelets in platelet-rich plasma and caused release of serotonin and ADP from platelets in platelet-rich plasma.     

Acute renal failure: factors influencing nephrology referral and outcome

We investigated the incidence, factors affecting referral and outcome of acute renal failure (ARF), in an unselected (predominantly Caucasian) population in the Grampian region of Scotland served by a single renal unit. Case-notes were examined for all patients with a serum creatinine > or = 300 mumol/l. ARF (311 patients) was defined as a temporary rise in serum creatinine > or = 300 mumol/l, or, if the patient died during the acute illness, clinical features indicating acute deterioration of previously normal renal function. Advanced ARF at presentation (51 of the 311 with ARF) was defined as a first recorded serum creatinine > or = 500 mumol/l. Patients were classified into low-, medium-, and high-risk groups according to presence of comorbidity and age. The annual incidence of ARF was 620/million population (pmp), that of advanced ARF 102 pmp. The age-related incidence of ARF ranged from 30 pmp in the age group (0-19 years) to 4266 pmp in the age group > 80 years. Overall, 22% were referred to a nephrologist (34% after excluding those with advanced cancer and age > 80 years). Referral of patients decreased from 100% in the age group 0-19 to 5% in those > 80 years. Referrals in the low-, medium- and high-risk groups were 75%, 30% and 14%, respectively. Patient survival at 2 years was 80%, 42% and 19% for low-, medium-, and high-risk groups, respectively (86%, 44% and 32% for referred patients). Referral and outcome in patients with ARF were significantly influenced by age and presence of comorbidity at presentation.     

Localization of authentic thromboxane A2/prostaglandin H2 receptor in the rat kidney

Using a polyclonal antibody against authentic thromboxane A2/prostaglandin H2 (TxA2/PGH2) receptor protein, we assessed the distribution of this receptor in the normal rat kidney by routine methods of immunofluorescence microscopy. The receptor localized both in glomeruli and in tubules. In the former, the distribution of the receptor was most prominent along the lumen of glomerular capillary loops. Parietal epithelial cells of the Bowman's capsule, podocytes and mesangial cells also demonstrated immunostainable receptor. In the tubules, the receptor localized most prominently at the base of the brush border of proximal tubules and at the luminal surface of thick ascending limbs and distal convoluted tubules. These observations point to sites that are likely to be targeted by thromboxane A2 in forms of renal injury characterized by enhanced synthesis of this eicosanoid.     

Acute renal failure associated with nonfulminant hepatitis A viral infection

Nonfulminant hepatitis A viral infection has rarely been associated with renal abnormalities, most commonly microscopic hematuria and minimal proteinuria. An unusual case is presented of a 37-yr-old female with serologically proven acute hepatitis A infection complicated by acute oliguric renal failure. The patient recovered, and laboratory tests returned to normal 1 month after initial hospitalization. Renal biopsy revealed acute tubular necrosis; dialysis was not necessary. The relevant world literature is reviewed.     

Halogen-substituted trimetoquinol analogs as thromboxane A2 receptor antagonists in platelets and aorta

Trimetoquinol (TMQ) is a non-prostanoid compound that blocks prostaglandin H2/thromboxane A2 (TXA2) receptor-mediated responses initiated by a prostaglandin (PG) H2 analog, U46619, in human platelets and rat aorta. Ring fluorine-substituted TMQ analogs selectively antagonized PG-dependent human platelet activation induced by U46619, arachidonic acid, collagen, ADP or epinephrine; and were about 300-fold less potent as inhibitors of PG-independent responses mediated by thrombin or bacterial phospholipase C. For each inducer of the PG-dependent pathway, the rank order of inhibitory potency was identical (TMQ > 8-fluoro-TMQ > 5-fluoro- TMQ). Iodine substitution yielded a similar rank order of antagonism against U46619-induced platelet activation (TMQ > 8-iodo-TMQ > 5-iodo-TMQ), and all TMQ analogs inhibited platelet aggregation in whole blood as well as in platelet-rich plasma. Inhibition of specific [3H]SQ 29,548 binding by TMQ analogs was highly correlated with inhibition of functional responses to U46619. Radioligand binding experiments using TMQ analogs with rat platelets showed no interspecies difference in comparison with human platelets. The rank order of inhibitory potencies for the fluorinated (but not iodinated) TMQ analogs changed in rat thoracic aorta with 8-fluoro-TMQ > TMQ > or = 5-fluoro-TMQ as antagonists of U46619-induced vascular contraction. These findings demonstrate that the primary mechanism of antiplatelet action of TMQ analogs is related to a blockade of TXA2 receptor sites, and ring-halogenated TMQ analogs distinguish between TXA2-mediated functional responses in vascular smooth muscle and platelets.     

Acute renal failure after snakebite: a report of four cases

The effects of FR139317 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1 H-azepinyl)]-carbonyl]amino-4-methyl-pentanoyl]amino-3[3-(1-methyl -1 H-indolyl)]propionyl]amino-3-2(2-pyridyl)propionic acid), an endothelin ETA receptor antagonist, on renal hemodynamics and urine formation were examined using anesthetized deoxycorticosterone acetate (DOCA)-salt hypertensive rats, in which renal perfusion pressure was protected from FR139317-induced hypotension with an aortic clamp. An intravenous injection of FR139317 (10 mg/kg) to sham-operated normotensive control rats produced no significant changes in renal hemodynamic and excretory responses. In DOCA-salt hypertensive rats, FR139317 caused sustained renal vasodilation. Urine flow and urinary excretion of sodium were increased significantly following drug injection. We suggest that endothelin-1 and the endothelin ETA receptor play an important role in water and sodium retention, and in renal vasoconstriction in this model of hypertension.     

Acute renal failure: controversies, clinical trials, and future directions

Acute renal failure (ARF) is an important clinical syndrome. Despite the frequent occurrence of ARF, nephrologists have not made major therapeutic inroads in the treatment or prevention of ARF. This article will speculate as to why it has been so difficult to gain a substantial foothold in the ongoing battle against ARF. First, some of the major controversies regarding the pathogenesis of ARF will be considered. Scientific debates regarding the mechanisms of ARF have greatly enriched the scientific literature, but may have slowed the development of clinically applicable therapies. Controversies regarding the treatment of ARF will then be discussed. Next, the fate of several recent clinical trials in ARF will be examined. Finally, the future directions that research in ARF may pursue will be contemplated.     

Acute renal failure in renal allograft recipients and patients with native kidneys

Techniques for the separation/concentration of micro-organisms from background food matrices can be applied to increase the speed of analysis and ease of isolation and detection of target micro-organisms. One recent example of such a technique is the immunomagnetic separation (IMS) procedure that has been used for the separation of specific micro-organisms from foods. This paper describes the use of a novel biosorbent consisting of a Salmonella-specific bacteriophage (phage) immobilized to a solid phase that was used for the separation and concentration of Salmonella from food materials. This work has shown that a Salmonella-specific phage-based biosorbent could remove Salmonella from culture fluid and separate Salmonella from suspensions of other Enterobacteriaceae. The ease of production of phage, high affinity of phage-cell interaction and the ability of phage to infect host cells in heterogeneous environments indicates the potential of such a biosorbent as the basis for a reliable separation system in food microbiological analysis.     

Acute renal failure in infants, children and adults

Acute renal failure (ARF) occurs in many critically ill patients regardless of age. A combination of events often seen in critical care settings, including shock, sepsis, hypoxia, and the use of potentially nephrotoxic medications, combine to make ARF an ongoing and important management issue in critical care medicine. Since the events leading to the development of ARF differ in infants, children, adults, and the elderly, the pathophysiology, clinical features, and treatment modalities do indeed have remarkable similarities among the different age groups.     

Changes in glomerular thromboxane A2 receptor expression and ligand binding following immune injury

Susceptibility of lipoproteins to oxidation is partly determined by their content in endogenous antioxidants, but also by the polyunsaturated fatty acids (PUFA)/monounsaturated fatty acids (MUFA) ratio. The aim of our study was to enrich human high-density lipoproteins (HDLs) with dioleoylphosphatidylcholine (DOPC) in order to modify the PUFA/MUFA ratio while maintainig the alpha-tocopherol/PUFA ratio constant and to appreciate the consequences of this enrichment before and after copper-induced oxidation. The enrichment of HDLs with DOPC was obtained by incubation of these lipoproteins with DOPC liposomes and further reisolation of HDLs. The consequent 40% HDL enrichment in MUFA was concomitant with a 35% loss in PUFA (MUFA/PUFA ratio = 1.43). The enrichment of HDLs with DOPC led to a 40% decrease in alpha-tocopherol content, which kept a constant alpha-tocopherol/PUFA ratio. The DOPC-HDLs exhibited a lower oxidizability by copper than the nonenriched HDLs (NE-HDLs), as shown by their twofold longer lag phase and the threefold lower propagation rate. Moreover, DOPC-HDLs led to a six- to sevenfold lower production of hydroperoxide molecular species from phosphatidylcholine and cholesteryl esters than NE-HDLs after 24 h copper oxidation. With regard to the cholesterol effluxing capacity, copper oxidation of HDLs led to a decrease of this property. However, our results clearly showed that DOPC enrichment of HDLs allowed us to keep a better effluxing capacity than in NE-HDLs after 24 h oxidation (22.3% vs 17.4%, respectively). Since apo A-I was degraded as well in DOPC-HDLs as in NE-HDLs, the better effluxing capacity of DOPC-HDLs could not come from a preserved integrity of apo A-I. It could be partly related to the improved fluidity of oxidized DOPC-HDLs compared to oxidized NE-HDLs, as shown by electron spin resonance data (correlation-relaxation time at 24 degreesC = 2.20 ns vs 3.00 ns after 24 h oxidation, in DOPC-HDLs and in NE-HDLs, respectively). Besides, it could also be hypothesized that the sevenfold lower content of phosphatidylcholine hydroperoxides in DOPC-HDLs than in NE-HDLs after 24 h copper oxidation could be involved in the better ability of oxidized DOPC-HDLs to mobilize cellular cholesterol.     

Acute renal failure in the llama (Lama glama)

40 thyroid cartilages were used to investigations, they were taken from bodies of people, died between the ages of 19-99, by the use of the endurance machine with controlled speed of the increase of deformation. It was observed that the durability for flexion and the inflexibility of the investigated cartilages depends on the level of the process of their ossification, that is estimated by the help of the radiological index of the ossification (RIO). On the other hand, the searches of durability forcing of the regions of cartilages that presented different levels of the ossification process, proved the heterogenicity of the structure of the cartilage, in which ossified parts are separated by zones, that did not submit to this process.