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PubMed2026

Integrated Network Pharmacology and Molecular Docking Analysis of Sishen Decoction Identifies Potential Targets and Pathways in Gout.

Gout is a disease characterized by hyperuricemia and the deposition of urate crystals in joints and soft tissues, leading to recurrent acute arthritis. Its increasing prevalence imposes substantial clinical and socioeconomic burdens. Sishen Decoction (SSD) has been used in the treatment of gout, but its potential molecular mechanisms remain unclear. This study applied an integrated network pharmacology and molecular docking approach to identify potential targets and signaling pathways associated with SSD in gout. Active compounds and corresponding targets of SSD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), while gout-related targets were collected from the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Overlapping targets were identified and used to construct a drug-component-target-disease network. A protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, followed by molecular docking using the docking server analysis module. A total of 37 bioactive compounds were associated with 116 overlapping gout-related targets. The top hub targets included TP53, IL6, IL1B, TNF, AKT1, EGFR, CASP3, JUN, BCL2, and MMP9. GO analysis suggested that these targets are involved in gene expression regulation and signal transduction. KEGG enrichment analysis indicated significant associations with the mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K-Akt), interleukin-17 (IL-17), and tumor necrosis factor (TNF) signaling pathways. Molecular docking predicted favorable interactions between key compounds and hub targets, with all binding energies of ≤-5 kcal/mol. These computational findings provide potential mechanistic hypotheses for the action of SSD in gout and may support future experimental validation.

Molecular Docking Simulation↗

PubMed1977

[Gout in the age (author's transl)].

The importance of the gout is growing in the GDR as its frequency has been increasing since the sixties. The gout is a disease of metabolism with the following accompanying phenomena: renal lesion in gout, hypertension, cardiac diseases and peripheral arterial diseases. Besides, there are proved relations between hyperuricemia and obesity, hyperlipoproteinemia, diabetes mellitus as well as steatosis hepatis. In describing the nature of the gout the peculiarities of age are stressed. The treatment of the gout depends on the clinical state.

Age Factors↗

PubMed1977

Secondary gout in hemoglobinopathies: report of two cases and review of the literature.

Although patients with hemolytic hemoglobinopathies characteristically are over-producers of urate, and hyperuricemia is frequently recognized, clinical gout has rarely been reported in such patients. Our evaluation of 2 premenopausal women with gout led to the diagnosis of previously unrecognized hemoglobinopathies (SC disease and CC disease). Investigation of these 2 patients and review of the reported cases of gout in patients with hemoglobin S or C disorders suggest that relatively minor abnormalities of renal function in these patients may lead to early development of significant hyperuricemia. With increasing lifespan of patients with hemolytic hemoglobinopathies and the likelihood of increased occurrence of renal function abnormalities, it is anticipated that gout will more frequently be responsible for joint symptoms in such patients.

Adolescent↗

PubMed1975

The radiology of gout. Review article.

The radiological features of gout are presented on the basis of a consecutive series of 64 in-patients and a review of the literature. Gout is a painful and potentially crippling disorder. Since fewer patients are referred with a classical acute attack due to the advent of more effective drug therapy, the radiologist may be presented with unusual or atypical cases. It is confirmed that there are no specific radiological features of gout. Provided a high index of suspicion be mai-tained, particularly in those groups of patients in whom secondary gout is common, a combination of signs may allow the diagnosis to be correctly inferred, leading to biochemical confirmation.

Acute Disease↗

PubMed1978

[Uptake of 2-C14 urate by erythrocytes in hyperuricemia and in gout (author's transl)].

The uptake of 2-C14 urate by erythrocytes was measured in 19 patients with primary hyperuricemia, 6 patients with secondary hyperuricemia, 17 patients with primary gout and 30 controls. The uptake of urate in patients with primary gout was significantly lower than in the controls. In contrast no such difference could be observed in patients with primary and secondary hyperuricemia. The uptake of labeled urate by erythrocytes from gouty patients is especially diminished in the early phase of the uptake kinetics. The possible relevance of this finding for the pathogenesis of urate precipitation in gout is discussed. Further, we consider the application of the tracer urate uptake by erythrocytes as an aid in the early diagnosis of gout.

Erythrocytes↗

PubMedDate not supplied

[Various epidemiological aspects of hyperuricemia and gout in Mexico: incidence and the cardiovascular risk factor].

We studied the prevalence and the risk factor among the patients of gout in Mexico. Research was conducted in the National Institute of Cardiology and in our private practice. Prevalence of hiperuricemia and gout in the Institute of Cardiology was of 1% (970 out of nearly 100,000 patients). We divided those cases of two subgroups: Reumatology patients (333) and Cardiovascular patients (529). In the first group primary gout was (96.3), and (50.32% in the second. Risk factor was quite different too: nephropathy 9.9%, lithiasis 9.3%, pyelonephritis 2.7%, cardioangiosclerosis 12.9%, aortosclerosis 6.6%, coronary insufficiency 6.3%, myocardial infarction 0.9%, arterial hypertension 24.6% obesity 56.1% and diabetes 9.9% in the Reumatology group; in the Cardiovascular one, nephropathy 14.3%, lithiasis 12.2%, pyelonephritis 7.1%, cardioangiosclerosis 62.7%, aortosclerosis 31.7%, coronary insufficiency 24.9%, myocardial infarction 29%, arterial hypertension 51%, obesity 54.8% and diabetes 20.4%. Among the private practice patients prevalence was of 10.1% (961). In an early age (39 years) in men and a later one for women (53 years). Other characteristics of epidemiology and risk factor are: primary gout 89%, atherosclerosis 5%, coronary disease 4.6%, lithiasis 4.7%, nephropathy 2%, pyelonephritis 1%, obesity 43%, and diabetes 4.6%. In an small group of patients of our private practice we made an exhaustive study of risk factor and the metabolic disorder of lipids. We found the following frequency: 9.3 of nephropathy, 31.2% of lithiasis, 18.7% of pyelonephritis, 68.9% of cardioangiosclerosis, 46.8% de coronary insufficiency, 9.3% of myocardial infarction, 68.7% of arterial hypertension, 68.7% of obesity and 18.7% of diabetes. In the lipid profile we found an increase in triglicerids and prebeta lipoprotein. We have amply discussed the relation between hiperuricemia and pathology considered as a risk factor from the genetic point of view as well as the metabolic and circumstancial aspect. From all that we concluded that risk is multifactorial.

Adult↗

PubMed2026

Efficacy and Safety of Ultra-Low Starting Dose Febuxostat Titration in Male Patients With Primary Gout.

BACKGROUND: Since gout is a common metabolic arthritis caused by urate crystal deposition, urate-lowering therapy (ULT) is clearly indicated, but the initiation of ULT frequently causes paradoxical acute flares that in turn impair patient adherence. OBJECTIVE: This study sought to assess the effectiveness and safety of an ultra-low-dose initiation strategy for febuxostat (10 mg/day) compared to the standard starting dose (20 mg/day) in reducing initiation-related flares while maintaining long-term urate control. METHODS: 120 male patients with primary gout presenting with acute arthritis were randomly assigned to initiate febuxostat at 10 mg/day (Group A) or 20 mg/day (Group B), with protocol-mandated biweekly titration. The primary outcomes were gout flare frequency over 24 weeks (assessed using Poisson regression), serum uric acid (SUA) target attainment, and the incidence of adverse events. RESULTS: Although both groups achieved comparable target SUA levels by week 24, Group A demonstrated a significantly lower overall flare incidence (36.7% vs. 70.0%; p < 0.001), along with a greater percentage of flare-free patients (70.0% vs. 46.7%; p = 0.016). Multivariable Poisson regression revealed that Group B had an approximately twofold higher risk of flares compared to Group A (Incidence Rate Ratio = 1.95; p = 0.012), with obese patients deriving the most pronounced benefit from the ultra-low-dose approach. To avert one additional flare, the calculated number needed to treat was 4.3. Additionally, the occurrence of clinically significant liver injury (ALT/AST > 3× ULN) was low in both groups, with 3.3% in Group A and 1.7% in Group B. Multivariable regression analysis confirmed that LDL-C is an independent predictor of ALT (β = 12.90, p = 0.009), while febuxostat dosage was not linked to hepatotoxicity. CONCLUSION: Initiating febuxostat at a dose of 10 mg/day with gradual titration demonstrates a superior safety profile by effectively reducing early acute flares without compromising long-term urate control, which is particularly advantageous for high-risk cohorts, including obese patients.

Humans↗

PubMed1979

Piroxicam in the treatment of acute gout: a multicentre open study in general practice.

Twenty-nine patients with acute gout were treated with piroxicam (40 mg daily for 5 days) in a multicentre general practitioner study. Pain relief was noticeable within 4 hours of the first dose and thereafter proceeded steadily, together with the early relief of other symptoms associated with acute gout. The prompt relief of symptoms was accompanied by a fall in serum uric acid. Piroxicam was well tolerated, eight experiencing side-effects that were mainly mild and gastro-intestinal in nature. The drug seems to be highly effective and safe in the treatment of acute gout.

Acute Disease↗

PubMed1977

Preliminary criteria for the classification of the acute arthritis of primary gout.

The American Rheumatism Association sub-committe on classification criteria for gout analyzed data from more than 700 patients with gout, pseudogout, rheumatoid arthritis, or septic arthritis. Criteria for classifying a patient as having gout were a) the presence of characteristic urate crystals in the joint fluid, and/or b) a topus proved to contain urate crystals by chemical or polarized light microscopic means, and/or c) the presence of six of the twelve clinical, laboratory, and X-ray phenomena listed in Table 5.

Acute Disease↗

PubMed1977

Gout disease. Its natural history based on 1,000 observations.

Gout disease in our country as both exogenous factors (dietary habits, professions, etc.) and endogenous factors (sex, inheritance, etc.) play a polygenic role in its incidence. Those conditions resulting in hyperuricemia (diseases, drugs, etc.) facilitate the clinical manifestations. But a genetic determinant in the articular reaction in front of an accumulation of uric acid crystals or in the development of such crystallization is a fundamental factor in the manifestation of the disease. In our series we were able to confirm the high incidence of arterial hypertension, renal lithiasis and renal participation in gout. The role of lead and of certain professions in favouring the hyperuricemia is suggested. A classification of gout, from a functional point of view, must include both the clinical form and the analysis of the whole renal function, and the renal handling of uric acid. This is mandatory not only for the diagnosis and prognosis of the disease but to set the basis of its adequate management.

Calculi↗

PubMed1978

The gout patient in general practice.

A study of the clinical profile of gout-diagnosed patients was undertaken within general practice in Great Britain. At the time of the first attack of acute gouty arthritis, the mean age was 52.3 years and 15.6% of the total 1077 patients were female. Males had an earlier clinical onset than females and the average frequency of attacks of acute gouty arthritis was 0.91 per patient year. Ten per cent of the cases were believed to be secondary gout, with diuretic therapy the most frequent cause. The sample showed a highly significant association between gout and the higher social classes, a family history among blood relatives in 23% of cases, tophi were noted in 4.6% of cases where sought and 38.2% of cases were 10% or more overweight and significantly heavier than a non-gouty population. The great toe joint was most frequently involved, both in the first episode and in all acute episodes combined. The most frequently occurring associated chronic condition was hypertension which was present in 27.8% of cases. Renal stones occurred in 6.1% and renal impairment in 2.2%. Only 20.4% of the patients were referred to hospital, with the younger being referred more frequently than the older. Those with joint involvement other than the great toe had a greater chance of being referred, as did those who also had angina pectoris, myocardial infarction and hypertension. Allopurinol appeared to be the drug of choice for long-term control therapy and phenylbutazone for the acute attack.

Adolescent↗

PubMed1977

The cartoon in doctor-patient communication. Further study of the Arthritis and Rheumatism Council handbook on gout.

A sample of 50 consecutive patients with gout was tested by means of a multiple-choice knowledge-testing questionnaire based on the Arthritis and Rheumatism Council's Gout: A Handbook for Patients. Patients were divided into two groups: (a) those tested with an illustrated booklet containing 89 cartoons, and (b) those tested with an unillustrated booklet with text exactly the same as in the illustrated booklet. No significant difference was observed in either the overall test scores between the two groups or between individual question scores. It was concluded that increasing the number of illustrations in the Arthritis and Rheumatism Council's handbook on gout had not significantly increased the value of this material as a communication aid. Certain sources of error have been discussed including the possibility of an 'interest factor' due to the inevitable interest patients have in reading about their own disease, and also the possibility that technical factors to do with page layout and picture/text imbalance might be responsible for failing to show differences between the two groups.

Cartoons as Topic↗

PubMed1979

Prevalence and incidence of the diagnosis of gout in Great Britain.

A study in gout of the incidence of diagnosis from 1971 to 1975 and of the prevalence at 31 December 1975 was carried out in a representative general practice sample comprising 64 practices and a population numbering 1 in 145 of the total population of Great Britain. The results show an annual incidence in Great Britain from 1971 to 1975 varying from 0.25 to 0.35 per 1000 and an overall prevalence at 31 December 1975 of 2.6 per 1000. The prevalence in England was found to be significantly greater than in the rest of Great Britain and that in Wales to be significantly greater than in Scotland. In 10% of the cases the gout was believed to be secondary, with induction by diuretics being the most frequent cause. The prevalence of primary gout was estimated to be 2.3 per 1000.

Adolescent↗

PubMed1978

High prevalence of hyperuricaemia and gout in an urbanised Micronesian population.

The prevalence of hyperuricaemia and gout was investigated in the Micronesian inhabitants of the highly urbanised central Pacific island of Nauru. Sixty-four per cent of men and 60% of women aged 20 years and over had hyperuricaemia--the highest prevalence rates yet reported for a population. The hyperuricaemia in men was accompanied by a high prevalence of clinical gout (6.9%). While the hyperuricaemia is probably genetic, the high prevalence of gout may be related to the environmental change from the traditional island style of living to one of almost complete Westernisation.

Adult↗

PubMed1978

Gout without crystals on initial synovial fluid analysis.

In five patients with acute arthritis in whom gout was eventually documented, an initial synovial fluid analysis failed to reveal urate crystals. Four of the patients were seen in one hospital during a period of 30 months in which 103 cases of gout were documented on initial aspiration. While this is an uncommon event, the importance of being able to make a definitive diagnosis of gout is such that re-aspiration of the same or other joints may be justified under certain circumstances.

Adult↗

PubMed1975

Normal activity of metabolic pathways involved in the formation and utilization of phosphoribosylpyrophosphate in erythrocytes of patients with primary metabolic gout.

The activity of metabolic pathways involved in the formation and utilization of phosphoribosylpyrophosphate (PRPP) was studied in. The erythrocytes of 34 patients with idiopathic metabolic gout. The activities of the oxidative pentose shunt, of the hypoxanthine-guanine and adenine phosphoribosyltransferases (HGPRT, APRT) and of PRPP synthetase, as well as the rates of PRPP generation and of adenine incorporation into nucleotides were found to be normal in the erythrocytes of all these patients. Four patients with metabolic gout due to enzymatic abnormalities, two relatives with partial deficiency of HGPRT and two relatives with mutant feedback-resistant PRPP synthetase, were studied for comparison. The significance of the results is discussed in relation to postulated mechanisms for purine overproduction in metabolic gout.

Adenine Phosphoribosyltransferase↗

PubMed1976

Patterns of phosphoribosylpyrophosphate and ribose-5-phosphate concentration and generation in fibroblasts from patients with gout and purine overproduction.

In the majority of patients with gout and excessive uric acid production, underlying enzyme abnormalities have not been identified. In the present study, measurement of both the rate of generation and concentration of phosphoribosylpyrophosphate (PP-ribose-P) and the concentration of ribose-5-phosphate in cultured cells were undertaken to establish a classification of purine overproducers to direct study of additional enzyme defects. Fibroblasts were cultured from 24 individuals assigned to 4 groups: group 1, 5 normal controls; group 2, 5 patients with gout and normal dialy urinary uric acid excretion (gouty controls); group 3, 7 patients with well-defined enzyme abnormalities and excessive urinary acid excretion (4 with hypoxanthine-guanine phosphoribosyltransferase deficiency and 3 with excessive PP-ribose-P synthetase activity); and group 4, 7 patients with gout and excessive uric acid excretion but without grossly abnormal activities of the above enzymes in erythrocyte lysates. In all 14 fibroblast strains from patients showing excessive production of uric acid (groups 3 and 4), rates of purine synthesis de novo and PP-ribose-P concentrations exceeded values for cells from control groups. Cells from group 3 patients with hypoxanthine-guanine phosphoribosyltransferase deficiency showed normal PP-ribose-P generation, while those with excessive PP-ribose-P synthetase activity demonstrated increased generation of this regulatory substrate. All strains from group 3 patients had normal ribose-5-phosphate concentrations. Five cell strains from group 4 patients showed one of the two patterns of abnormalities in these measurements seen in strains from group 3 patients: two resembled hypoxanthine-guanine phosphoribosyltransferase-deficient cells, and three resembled cells with excessive PP-ribose-P synthetase activity. Analyses of erythrocyte enzyme preparations from two of these patients in group 4 have led to identification of a kinetic variant of each enzyme as predicted from the foregoing patterns. Two additional group 4 cell lines that showed increased ribose-5-phosphate concentrations in addition to increased PP-ribose-P concentrations and generation were classified in a separate subgroup, since in the individuals excessive purine synthesis appeared to result from increases ribose-5-phosphate concentration, leading to increased availability of PP-ribose-P. No abnormality in either hypoxanthine-guanine phosphoribosyltransferase or PP-ribose-P synthetase has been found in erythrocyte preparations from one patient so classified.

Adenine Phosphoribosyltransferase↗

PubMed1976

Lesions resembling gout in patients with rheumatoid arthritis.

Although roentgenographic appearances are seldom important in establishing the diagnosis of rheumatoid arthritis or gout, atypical appearances of individual lesions may confuse the distinction between these two conditions. Sixteen patients with rheumatoid arthritis were selected to illustrate joint and soft tissue lesions which resemble gout. The lesions are divided into five broad categories on the basis of the appearance and sites of bone erosion as well as the nature of soft tissue changes. Symmetrical bilateral joint involvement was found to be especially helpful in distinguishing rheumatoid arthritis from gout.

Arthritis, Rheumatoid↗