The excretion of uric acid in man has been of great interest because of its importance as an end product in purine metabolism as well as of its role in causing gout. There are many differences in the modes of renal handling of urate among various species of animals. Uric acid actively secreted by the renal tubules of most vertebrate including amphibians, reptiles, and birds. On the other hand, in most mammals net tubular reabsorption of urate appears to be occurred with some exception, such, as Dalmatian dog. In the rabbits, however, the mechanism of renal excretion of uric acid has long been a subject of controversial results. Within a given group it was possible to find individuals with either net secretion or net reabsorption of urate depend on the experimental conditions. Excretion of urate can be depressed or enhanced by a variety of drugs belonging mainly to the aromatic acid group. Diodrast, probenecid, cinchophen and salicylates have been reported as uricosuric agents, on the other hand, lactate, benzoate, pyrazinoic acid, acetazolamide and chlorothiazide are known to be contraindicated to use for the patient with gout since these agents depress the excretion of uric acid from the kidney. However, complex and sometimes the paradoxical effects on the urate excretion by those above mentioned drugs are not uncommon. The experiments were designed to investigate the mechanisms of renal handling of urate as well as the effects of variety of drugs on the tubular transport of uric acid in the rabbits. Male or female white rabbits, from 1.5 to 2.5 kg in weight, were used. The experimental methods used in these studies were clearance, stop-flow, and retrograde injection techniques. The effects of saline, salicylate, chlorothiazide and probenecid were investigated in each experimental conditions. Results of the experiments were summarized as follows; 1. In the rabbits, the rate of urate clearance was always lower than the rate of inulin clearance. The filtration fraction of the urate was one third on an average, therefore, it is estimated that approximately two thirds of filtered urate was reabsorbed. 2. In the kidneys of rabbits, the urate clearance was increased significantly by administration of chlorothiazide and decreased by probenecid. The administration of salicylate had no effect on the rate of urate clearance. The filtration fraction of urate was increased by chlorothiazide and decreased by probenecid. 3. In the stop-flow studies, the U/P ratio of urate was higher than the U/P ratio of inulin in the proximal region, indicating the secretion of uric acid in the proximal tubules. The proximal peak was increased by chlorothiazide and inhibited by probenecid.4. In the retrograde injection studies, the reabsorption of urate in the proximal region was observed, and these reabsorptive transport of urate was depressed by either probenecid or by chlorothiazide. 5. No distal tubular activity was observed under any of these experimental conditions concerning urate transport. The results of these experiments show that probenecid inhibits both secretory and reabsorptive transport of uric acid in the kidney of the rabbits. The enhancement of secretory transport of urate by chlorothiazide in the clearance study was due to the secondary action of chlorothiazide which inhibits the reabsorptive transport of urate in the proximal tubules. It is evident that the urate transport in the kidneys of rabbits is bidirectional nondiffusive flux both secretory and reabsorptive directions in the proximal tubules.
Sixty-six dogs diagnosed with cystolithiasis at animal clinics in the Busan area between April 2002, and April 2003, were reviewed. The chemical analysis of cystoliths from 66 dogs indicated that the predominant mineral component was struvite (45 dogs), calcium oxalate (14 dogs), or urate (6 dogs). Animals affected with struvite were grouped into four (s-1; struvite only, s-2; struvite mixed with lesser quantities of calcium oxalate or ammonium urate, s-3; nuclei and lamination, s-4; struvite nucleus surrounded by other minerals), with calcium oxalate into six(o-1; calcium oxalate monohydrate only, o-2; calcium oxalate dihydrate only, o-3; combination of calcium oxalate monohydrate and dihydrate, o-4; calcium oxalate nucleus surrounded by other minerals, o-5; 100% calcium oxalate monohydrate nucleus surrounded by 100% calcium oxalate dihydrate, o-6; mixed calcium oxalate monohydrate nucleus surrounded by mixed calcium oxalate dihydrate), and with urate into two(u-1; ammonium acid urate only, u-2; ammonium acid urate mixed with lesser quantities of other minerals). In this study, the numbers of 4 groups of struvite were (s-1; 10, s-2; 9, s-3; 21, s-4; 5), 6 groups of calcium oxalate were (o-1; 0, o-2; 1, o-3; 2, o-4; 3, o-5; 2, o-6; 6), and 2 groups of urate were (u-1; 6, u-2; 0). The data from each group was analyzed and compared. Shih Tzu(14 cases), Yorkshire terrier(10 cases), mixed-breed(10 cases) and Miniature schnauzer(7 cases) were more frequently affected than the other breeds. Females(40 cases) were affected more than males(26 cases). Twenty-nine dogs had cystoliths associated with a bacterial urinary tract infection, and uroliths tended to recur. We conclude eradication of urinary infection along with appropriate food (e.g. prescription diet) with client compliance should help in reducing the incidence or severity of the disease.
Hana Choi;Jeongah Ryu;Seunghun Lee;Yeo Ju Kim;Soyoung Bang
Journal of the Korean Society of Radiology
/
v.84
no.1
/
pp.212-225
/
2023
Purpose We retrospectively investigated the characteristics of patients with monosodium urate (MSU) deposits of the hand and wrist on dual-energy CT (DECT) compared to those without. We also attempted to determine the pattern of MSU distribution in DECT. Materials and Methods In total, 93 patients were included who had undergone DECT for evaluation of the hand or wrist pain under the clinical impression of gouty arthritis. The total volume of MSU deposits on DECT was calculated and the pattern of MSU distribution on DECT was analyzed. Also, the level of the serum urate at the time of DECT and the highest level of the serum urate of the patients were obtained from their records and the relationship between MSU and serum urate level was evaluated. Results The range of the volume of MSU deposits on DECT was 0.01-16.11 cm3 (average: 1.07 cm3). The average level of serum urate was significantly higher in the MSU positive group than that in the MSU negative group. MSU deposits were most frequently observed in the wrists followed by fingers and digitorum tendons. Conclusion On DECT, MSU deposits were most frequently detected in the wrist and related with high serum urate level.
The characteristics of probenecid effect on renal urate excretion in the cat were studied by clearance method and compared with those in the rabbit. In the cat GFR was $3.03{\pm}0.09\;ml/min{\cdot}kg$, and endogenous plasma urate concentration was $1.12{\pm}0.57\;{\mu}g/ml$, which is less than that in the rabbit $(3.33{\pm}0.46\;{\mu}g/ml)$. In the rabbit, $FE_{ur}$ was $1.76{\pm}0.08$ and net urate secretion was observed, while, in the cat $FE_{ur}$ was $0.70{\pm}0.02$ and net reabsorption was observed. In the cat $FE_{ur}$ was dependent on urine flow and independent of plasma urate concentration. In the rabbit $FE_{ur}$ was suppressed by infusion of probenecid $(30\;mg/kg\;-0.6\;mg/kg{\cdot}min)$ into femoral vein. In the cat the same dose of probenecid increased $FE_{ur}$ and concomitantly increased urine flow. Thus, an increase in $FE_{ur}$ by probenecid could be considered to be resulted from a change in urine flow. In the cat infusion of probenecid $(2.5\;mg/kg{\cdot}min)$ into renal artery markedly suppressed $FE_{P\;A\;H}$, but the effects on $FE_{ur}$ and urine flow were similar to those when probenecid was infused into femoral vein. These results indicate that in the cat kidney urate filtered through glomerulus is reabsorbed by a probenecid-insensitive mechanism with no evidence for net secretion.
Objective: The aim was to identify the inhibitory effects of Flos Bombacis Malabarici(FBM) on Monosodium Urate (MSU)-induced gout in rats. Materials and Methods: After pretreatment of FBM I (50mg/kg), FBM II (125mg/kg) for seven days followed by injection of MSU solution, the various indicators related to gout were measured, such as hematological and serum levels and including joint inflammation. Also, it was investigated whether FBM directly inhibits the activity of xanthine oxidase in vitro. Results: As a result of this study, FBM didn't show the cytotoxicity in Jurkat cells, but it showed significant inhibition of activity of xanthine oxidase in vitro. FBM slightly inhibited joint inflammation induced by MSU though not with statistical significance. FBM partially decreased MSU-induced AST, ALT, BUN, creatinine, WBC, ESR elevation and significantly decreased MSU-induced uric acid in serum. Conclusion: These results suggest that FBM has therapeutic effects that are applicable to prevention and treatment of gout. and should be further investigated.
Journal of Physiology & Pathology in Korean Medicine
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v.20
no.2
/
pp.388-393
/
2006
The aim was to identify the inhibitory effects of Radix Rosae Laevigatae(RRL) on Monosodium Urate(MSU)-induced gout in rats. After pretreatment of RRL I (125mg/kg), RRL II (50mg/kg) for seven days followed by injection of MSU solution, the various indicators related to gout were measured, such as hematological and serum levels and including joint inflammation. Also, it was investigated whether RRL directly inhibits the activity of xanthine oxidase in vitro. As a result of this study, RRL didn't show the cytotoxicity on cell proliferation, but it showed significant inhibition of activity of xanthine oxidase in vitro. RRL slightly inhibited joint inflammation induced by MSU though not with statistical significance. RRL partially decreased MSU-induced BUN, creatinine, WBC, ESR elevation and significantly decreased MSU-induced AST, ALT, uric acid in serum. These results suggest that RRL has therapeutic effects that are applicable to prevention and treatment of gout, and should be further investigated.
Journal of Physiology & Pathology in Korean Medicine
/
v.19
no.6
/
pp.1534-1540
/
2005
In order to testify the urate lowering effects of Daihwangmudan-tang(DMT), ICR mice were injected monosodium urate into the abdominal cavity and then DMT was administered on 2 and 4 days after Injection. Uric acid and triglyceride were measured as hematological indices of gout, and some genes related with this change were identified by ACP based GeneFishing PCR method and direct sequencing. From this experiment, DMT highly decreased the blood levels of uric acid and significantly suppressed and lowered the acute increment of triglyceride level. There were 11 differentially expressed genes(DEG) having relations with positive actions of DMT, and 4 major genes in the middle of DEGs were sequenced; Mfap 2, jagged 2, Hsd17b7, DkkI-1, These genes were supposed that several mechanisms through interleukin 1 and T-cell anergy, LDL cholesterol metabolism, wnt pathway would be related with the anti-inflammation effect against gout.
The anti-inflammatory effect of Spirulina fusiformis on monosodium urate crystal-induced inflammation in mice has been investigated and compared with the non-steroidal anti-inflammatory drug Indomethacin. The paw volume, lysosomal enzyme activities, lipid peroxidation, anti-oxidant status and inflammatory mediator tumour necrosis factor-$\alpha$ were studied in control and monosodium urate crystal-induced mice after oral administration of Spirulina platensis in an experimental model for gouty arthritis. In the induced mice, the levels of lysosomal enzymes, inflammatory mediator tumour necrosis factor-$\alpha$, lipid peroxidation and the paw volume increased significantly, whereas the antioxidant status decreased when compared to control mice. $\beta$-glucuronidase and lactate dehydrogenase level were also found to be increased in untreated monosodium urate crystal-incubated polymorphonuclear leucocytes. After the oral administration of Spirulina fusiformis, the physical and biochemical changes observed in monosodium urate crystal-induced animals were significantly restored to near normal levels. The results clearly indicated the anti-inflammatory role of Spirulina fusiformis, a promising drug for gouty arthritis.
Objective : To identify the inhibitory effects of Commiphora Myrrha (CM) on monosodium urate (MSU)-induced gout model in rats. Materials and Methods: After pretreatment with CM-I (125mg/kg) or CM-II (50mg/kg) for 7 days followed by ones injection of MSU solution. the various indicators related to gout were measured on hematological and serum level including joint inflammation, Also, it was studied whether FBM directly inhibits the activity of xanthine oxidase in vitro. Results : As a result of this study, CM didn't show cytotoxicity in Jurkat cells, but it showed significant inhibition of activity of xanthine oxidase in vitro. CM slightly inhibited joint inflammation induced by MSU though not with statistical significance. CM partially decreased MSU-induced albumin, globulin, AST, ALT, BUN, creatinine. WBC, platelet count and ESR level and significantly decreased MSU-induced uric acid in serum. Conclusion : These results suggest that CM has therapeutic effects that are applicable to prevention and treatment of gout, and should be further investigated.
In order to study the Effects of yindong(LC) on the variation of blood and joint value the gout induced by microcrystalline sodium urate in rats, for LC is one of the important medicine on gout. After pretreatment of LC(50, 500mg/kg) for 5days, the Effects of LC was evaluated on Serum albumin, Serum globulin, glutamate dxalacetate transminase(AST), glutanate pyruvate transminase(ALT), blood urea nitrogen(BUN), Serum creatitine, Serum uric acid, xanthine oxidase activity, Erythrocyte Sedimentation Rate(ESR), WBC, platelet were measured. The results were obtained as follows : Joint value Increase ratio was not significantly decreased in all LC taken groups compared with the control group. Serum albumin was significantly different in all LC taken groups compared with the control group and Serum globulin was significantly dicreased in 500mg/kgLC taken group compared with the control group. Serum AST, ALT were significantly dicreased in 500mg/kgLC taken group compared with the control group. Serum BUN was significantly decreased in all LC taken groups and Serum creatinine was significantly decreased in 500mg/kgLC taken group compared with the control group. Serum uric acid was significantly different in 500mg/kgLC taken group, and changes in xanthine oxidase activity was significantly decreased in 500mg/kg, 50mg/kgLC taken group. ESR was significantly decreased in all LC taken groups compared with the control group. WBC, platelet count were significantly decreased in 500mg/kgLC taken group compared with the control group. From above results it may be concluded that Yindong can be used for treatment and preventive medcine of gout induced by microcrystalline sodium urate in clinic.
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