Biomedical subjects

A M Rofe

Publications and source records attributed to A M Rofe.

At least 55 records · Page 3Linked to original sources

PubMed1994

Formation of the L-cysteine-glyoxylate adduct is the mechanism by which L-cysteine decreases oxalate production from glycollate in rat hepatocytes.

Formation of thiazolidine-2,4-dicarboxylic acid, the L-cysteine-glyoxylate adduct, is the putative mechanism by which L-cysteine reduces hepatic oxalate production from glycollate [Bais, Rofe and Conyers (1991) J. Urol. 145, 1302-1305]. This was investigated in isolated rat hepatocytes by the simultaneous measurement of both adduct and oxalate formation. Different diastereoisomeric ratios of cis- and trans-adduct were prepared and characterized to provide both standard material for the enzymic analysis of adduct in hepatocyte supernatants and to investigate the stability and configuration of the adduct under physiological conditions. In the absence of L-cysteine, hepatocytes produced oxalate from 2 mM glycollate at a rate of 822 +/- 42 nmol/30 min per 10(7) cells. The addition of L-cysteine to the incubation medium at 1.0, 2.5 and 5.0 mM lowered oxalate production by 14 +/- 2, 25 +/- 3 (P < 0.05) and 38 +/- 3% (P < 0.01) respectively. These reductions were accompanied by almost stoichiometric increases in the levels of the adduct: 162 +/- 6, 264 +/- 27 and 363 +/- 30 nmol/30 min per 10(7) cells. Adduct formation is therefore confirmed as the primary mechanism by which L-cysteine decreases oxalate production from glycollate. As urinary oxalate excretion is a prime risk factor in the formation of calcium oxalate stones, any reduction in endogenous oxalate production is of clinical significance in the prevention of this formation.

Animals↗

PubMed1994

Effects of insulin and insulin-like growth factors on protein and energy metabolism in tumour-bearing rats.

The effects of insulin-like growth factor-1 (IGF-I), and a more potent variant LR3-IGF-I, which binds poorly to IGF-binding proteins, were investigated in rats bearing a mammary adenocarcinoma. The effect of insulin, either alone or in combination with LR3-IGF-I, was also investigated. Peptides were infused via osmotic minipumps for 6-7 days after tumour size reached 5% of body weight. Infusion of IGFs alone at either 200 or 500 microgram/day significantly decreased food intakes as well as circulating levels of insulin and glucose, and consequently failed to promote muscle protein accretion in the host. Tumour growth was increased by the IGFs, especially by LR3-IGF-I, even though these peptides did not promote growth of the adenocarcinoma in cell culture. Infusion of LR3-IGF-I, and to a lesser extent IGF-I, led to decreased rates of muscle protein synthesis and increased muscle protein breakdown, but each of these measures was closely related to the final tumour burden (r2 = 0.454 and 0.810 respectively; P < 0.01) and possibly resulted from a decrease in substrate supply to the host tissues. Insulin infusion (100 micrograms/day) increased food consumption by more than 50% and significantly decreased tumour growth. Insulin and LR3-IGF-I had a synergistic effect on host weight, which increased by 19.1 +/- 1.9, -1.1 +/- 4.7 and 37.9 +/- 1.5 g for insulin, LR3-IGF-I and combined treatments respectively. Carcass protein was increased by more than 10% with insulin treatment, due to increased rates of synthesis and decreased rates of muscle protein breakdown, but LR3-IGF-I had no positive effect on carcass protein accretion, either alone or in combination with insulin. Similarly, the amount of carcass fat was increased almost 2-fold by insulin treatment, whereas it was decreased by 30% by LR3-IGF-I. These changes may have arisen either from direct hormone effects on metabolism or from the indirect effects of food intake, or both. Our results suggest that IGF administration may exacerbate an insulin insufficiency associated with the tumour-bearing state and further decrease metabolic substrate supply to the host. This can be overcome by co-infusion of insulin.

Adenocarcinoma↗

PubMed1994

Wasting in adjuvant-induced arthritis and its relationship to plasma zinc, copper and liver metallothionein.

The appearance of joint inflammation (JI) 14 days after the injection of adjuvant (AJ) in the tail of rats is associated with a cachectic syndrome which is characterised by marked weight loss (WL). The degree of weight loss was examined in relation to the extent of change in other markers of inflammation including increased plasma copper (pCu), decreased plasma zinc (pZn) and increased hepatic metallothionein (hMT). At 14 days post-AJ injection, arthritic rats showed the following changes, relative to the controls: body weight, 12% decrease, pZn, 50% decrease; pCu, 90% increase and hMT, 11-fold increase (all p < 0.001). Significant relationships were observed between JI, WL, pZn and hMT. The following coefficients of determination (r2) were observed; JI and WL, -0.530, JI and pZn, -0.485; JI and hMT, 0.286; WL and hMT, -0.510 (all p < 0.007). There was a strong relationship between the decreased pZn and increased hMT; r2 = 0.456 (p < 0.001). While increased pCu was clearly associated with AJ-arthritis in these rats, there was no quantitative relationship between the extent of change in pCu and the other parameters measured (r2 all < 0.01). The highest correlation observed was between pZn and WL (r2 = 0.637, p < 0.001). While the initial depression of pZn may be the result of increased hepatic hMT levels, longer term reductions in pZn levels are linked to systemic inflammation, the degree of arthritis and associated weight loss.

Animals↗

PubMed1994

Metallothionein and zinc homeostasis during tumor progression. Effect of methotrexate treatment.

Zinc homeostasis was studied during the induction, growth, and methotrexate (MTX) treatment of Dark Agouti rat mammary adenocarcinomas (DAMA). A progressive fall in plasma Zn concentration (pZn), significant at a tumor burden of less than 1% body weight (bw), was sustained during tumor enlargement to give a 54% reduction in pZn at 16.3% bw (n = 6/group). The hypozincemia was attributed to the increasing Zn demand for tumor growth. Zn content of the 16.3% bw tumors equaled that of muscle (normally 60% of total body Zn). Tumor metallothionein (tMT) was sufficient to bind < 3% of total tumor Zn, and hepatic MT (hMT) remained at basal concentrations during early tumor growth, doubling only in the presence of significant necrosis in large tumors. Methotrexate (MTX, 0.5 mg/Kg im x 2 d) at respective tumor burdens of 5 and 10% bw (n = 9, 10/group) gave 2 therapeutic effects, dependent on tumor size: 1.5% bw tumors in 7 rats remained close to their original size until experiment end when pZn, hMT, and tMT were typical of 5% bw untreated tumors. 2. Tumors in 5 rats given MTX at 10% bw had marked subcapsular necrosis and regression to a size similar to those in group 1; pZn returned toward normal, whereas hMT was 6 times its 5% bw counterpart. Host weight loss was significantly reduced, as were tumor-associated changes in plasma glucose and calcium. In summary, neither tMT nor hMT appears to play a role in the hypozincemia that follows DAMA Zn sequestration and growth. Critically timed MTX can result in tumor regression and return of plasma Zn, Ca, and glucose toward normal. This is associated with an increase in hMT and reduction in host weight loss, suggesting a flow of Zn from the resorbing tumor to the host, enabling the synthesis of hMT and retention of host structural proteins.

Adenocarcinoma↗

PubMed1994

The efficacy of (L)-2-oxothiazolidine-4-carboxylate (OTC) and (L)-cysteine in reducing urinary oxalate excretion.

The effects of orally administered (L)-cysteine and (L)-2-oxothiazolidine-4-carboxylate (OTC) on urinary oxalate excretion were investigated in male Porton rats, as (L)-cysteine has been shown to form an adduct with glyoxylate in vitro. Feeding of OTC (204 +/- 1 mg. per day) for 5 days increased urinary cyst(e)ine, p < 0.001; sulphate, p < 0.001; phosphate, p < 0.05; and calcium, p < 0.05; and decreased urinary pH, p < 0.001. In addition, OTC feeding significantly decreased urinary oxalate excretion when compared with controls, p < 0.05 (delta OTC-delta Control -4.26 +/- 1.55 nmol./day/gm.). In the 5-day period after cessation of OTC feeding, all urinary parameters returned to control levels. At the completion of this recovery period there were no significant differences in any of the clinically significant plasma parameters. When fed for 22 days (191 +/- 3 mg. per day) OTC decreased urinary oxalate compared with controls, p < 0.05 (delta OTC-delta Control -9.47 +/- 4.24 nmol./day/gm.). Other urinary parameters (uric acid, magnesium, calcium, phosphate, creatinine, pH and volume) were not significantly altered by OTC feeding. Again, at the completion of this feeding period there were no significant differences in any of the clinically significant plasma parameters. (L)-cysteine feeding for 5 days (184 +/- 10 mg. per day) increased urinary sulphate, p < 0.001; and magnesium, p < 0.05, and decreased urinary pH, p < 0.001. In addition, (L)-cysteine feeding did not significantly change urinary oxalate excretion when compared with the controls (delta(L)-Cysteine-delta Control -2.94 +/- 2.14 nmol./day/gm.). However, at the completion of this feeding period, plasma urate, p < 0.02; and glucose, p < 0.05, were decreased, and plasma potassium, p < 0.01, was increased. these results indicate that orally administered OTC is effective in reducing urinary oxalate excretion without altering plasma biochemistry. It is suggested that (L)-cysteine-glyoxylate adduct formation is the mechanism by which OTC reduces urinary oxalate excretion through a reduction in endogenous oxalate production.

Animals↗

PubMed1994

Metabolic consequences of methotrexate therapy in tumour-bearing rats.

The metabolic response of the tumour-bearing host to methotrexate (MTX) therapy was investigated with particular attention to effects resulting from MTX-induced anorexia. Biochemical changes in female Dark Agouti rats bearing mammary adenocarcinomas and treated with MTX (0.5 mg/kg, 2 i.m. injections, 24 h apart) were compared with untreated (CON) tumour-bearing rats, and tumour-bearing rats pair-fed (PF) to the MTX group. MTX treatment halted progression of the tumour (tumour 6% of bodyweight) while the tumour burden doubled in the CON and PF groups. A number of biochemical and haematological changes were specific to MTX treatment and did not result from decreased food intake. MTX treatment was associated with significantly decreased plasma calcium, bilirubin, alkaline phosphatase, aspartate aminotransferase and the total white cell count. Decreases in plasma albumin and total protein concentrations were observed in both MTX and PF rats. Other parameters commonly used to assess renal and liver function were not significantly affected by MTX. MTX reversed the hypoglycaemia, hyperketonaemia and hypertriglyceridaemia induced by tumour-bearing. In contrast, PF rats had an even more pronounced hypoglycaemia and hyperketonaemia than the CON rats. Measurement of glucose uptake in vivo with 2-deoxy[U-14C]-glucose showed that MTX treatment halved the glucose requirement of the tumour (8.2% of bodyweight compared to 12.2% in the control). It is concluded that the potentially adverse effects of MTX treatment on host metabolism are outweighed by the beneficial effects of a reduced metabolic demand resulting from inhibition of tumour progression.

Adenocarcinoma↗

PubMed1993

Influence of season, age, and sex on renal stone formation in South Australia.

OBJECTIVE: To investigate trends in renal stone formation in the South Australian population, between 1977 and 1991 (3634 stones), with respect to age, sex and seasonal variation. RESULTS: The frequency of the different stone types was: calcium oxalate (with or without phosphate), 68%; uric acid, 17%; infection stones (magnesium ammonium phosphate), 12%; and pure calcium phosphate, 3%. No significant seasonal variation was observed with calcium oxalate or calcium phosphate stones. The incidence of uric acid stones increased significantly during summer and autumn (P < 0.001 and P < 0.01 respectively), and that of infection stones decreased significantly during spring and summer (P < 0.05 and P < 0.01 respectively). Calcium oxalate, uric acid and calcium phosphate stones were more frequent in male subjects; male to female ratio 2.8:1, 3.7:1 and 1.4:1 respectively. However, there was an increased frequency of calcium oxalate stones in women 20 to 25 years of age; male to female ratio 0.7:1. Infection stones were more common in female subjects; male to female ratio 0.7:1. CONCLUSIONS: This study demonstrates significant seasonal variation in uric acid and infection stones. Men are at a higher risk of forming stones than women, with the exception of infection stones. Additionally, with calcium oxalate stones, women may have distinct periods of higher risk. This study confirms that calcium oxalate stones are the most common stone type, which is in accordance with studies from other industrialised countries.

Adult↗

PubMed1993

Metallothionein induction in freshly isolated rat hepatocytes.

The control of metallothionein (MT) synthesis was investigated in freshly prepared rat hepatocytes in experiments of short-term duration. Viability and metabolic function were maintained in incubations of 6-h duration. MT synthesis was measurable in hepatocytes from fed rats at Zn concentrations down to 1 microM. Zn and dexamethasone induced concentration-dependent increases in the synthesis of MT with maximal increases above the 5-h control of 3.2- and 2.5-fold, respectively. Zn induction of MT was first measurable at 2 h and was inhibited by actinomycin C. Although initial (0 h) MT concentrations in hepatocytes from fasted rats were double those from fed rats, after 6-h incubation in the presence of 50 microM Zn, the fasted rat hepatocytes showed only half the MT concentrations of the fed rat hepatocytes. Glucagon and interleukin-6 (IL-6) were less effective inducers and increased MT synthesis by 28 and 17%, respectively. IL-6 (100 U/mL) was found to have an additive effect on MT synthesis above that of Zn alone (1-50 microM) or Zn plus dexamethasone (1 microM). A supernatant from LPS-stimulated macrophages increased MT synthesis by 40%. The basal MT synthesis was not increased by either tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 (IL-1). All incubations were carried out in the presence of RPMI 1640 medium with Hepes (20 mM), bicarbonate (24 mM), and fatty acid-free albumin (FAFA; 0.5% w/v). MT synthesis was also seen using Krebs bicarbonate buffer with glucose (10 mM), Hepes (20 mM), and FAFA (0.5% w/v), and although the level of MT synthesis was less than in RPMI, the increases in concentrations of MT at 5 h were 225, 139, 36 and 20% for Zn, dexamethasone, glucagon, and control, respectively. It is concluded that MT synthesis occurs in freshly prepared hepatocytes and that these cells are responsive to some of the established inducers of MT. This system enables the study of MT synthesis in individual rats in various metabolic and pathological states.

Animals↗

PubMed1993

Corticosterone enhances the zinc and interleukin-6-mediated induction of metallothionein in cultured rat hepatocytes.

The regulation of metallothionein induction in cultured rat hepatocytes was investigated with Zn, hormones, cytokines and either the synthetic glucocorticoid, dexamethasone, or the endogenous rat glucocorticoid, corticosterone. A concentration-dependent increase was seen with Zn (two- to fivefold increase in 24 h, Zn 10-50 mumol/L). Dexamethasone at 1 mumol/L increased metallothionein synthesis by fourfold that of the controls. Maximal metallothionein concentrations of 17-fold the control value were seen with 50 mumol/L Zn and 1 mumol/L dexamethasone. Interleukin-6 (1 x 10(5) U/L) alone did not induce metallothionein but increased it 35-65% with Zn+dexamethasone. Like dexamethasone, corticosterone had a dose dependent effect on metallothionein and synergy with Zn and Zn+interleukin-6. Dexamethasone was approximately 100 times more potent than corticosterone at 10-100 mumol/L. Physiological concentrations of corticosterone (1 mumol/L) when added alone, with Zn (10 mumol/L), and with Zn+interleukin-6 resulted in inductions of 2.2, 5.0 and 7.4-fold above the control cultures. Glucagon (1 mumol/L) had no independent effect but increased metallothionein by 31% and 33% with Zn(10 mumol/L)+dexamethasone (1 mumol/L) and Zn-dexamethasone+interleukin-6, respectively. There was no accumulation of metallothionein with interleukin-1 beta, tumor necrosis factor alpha or interferon gamma (1 x 10(5) U/L) alone, but interleukin-1 beta and tumor necrosis factor alpha enhanced the response obtained with Zn+dexamethasone with and without interleukin-6. Insulin (100 U/L) alone, caused metallothionein accumulation and further enhanced the response seen with Zn+dexamethasone+interleukin-6+glucagon. No additional enhancement was seen with interleukin 1 beta+tumor necrosis factor alpha+interferon. The results demonstrate that concentrations of corticosterone in rats with experimental inflammation facilitate metallothionein induction with Zn and interleukin-6.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Changes in plasma zinc, copper, iron, and hepatic metallothionein in adjuvant-induced arthritis treated with cyclosporin.

The early changes in hepatic metallothionein (MT) and plasma zinc (Zn), copper (Cu), and iron (Fe) were investigated during the induction of adjuvant (AJ) arthritis in rats in conjunction with cyclosporin (CsA) treatment. Plasma Zn decreased after AJ injection (60% of control values at 8 h), and this was associated with a 4.5-fold increase in hepatic MT at 8 h. Plasma Zn was lowest at 16 h (40% of control), whereas hepatic MT concentrations increased to a maximum of 20-fold at 16 h. Changes in plasma Fe paralleled those of Zn, whereas plasma Cu levels were increased. Plasma metal and hepatic MT concentrations returned toward normal from d 1-7. At d 14, when marked paw swelling was apparent, hepatic MT and plasma Cu were again increased and plasma Zn decreased. Administration of CsA decreased MT induction in rats injected with AJ and also caused a marked recovery in plasma Zn and Fe levels. These changes were small but significant even in the early stages (up to 24 h) after AJ injection and were followed by a sustained improvement in all parameters, corresponding to the nonappearance of clinical arthropathy in CsA-treated rats. TNF-alpha and IL-6 production by peritoneal macrophages isolated from AJ-injected rats was significantly decreased by CsA treatment at d 7 and 14. The inhibition of hepatic MT induction during acute and chronic inflammation by cyclosporin emphasizes the role of the immune system in altered metal homeostasis in inflammation.

Animals↗

PubMed1992

Beneficial effects of endotoxin treatment on metabolism in tumour-bearing rats.

The effects of endotoxin treatment on host metabolism in tumour-bearing rats were investigated. Metabolism in control rats (non-tumour-bearing) was slightly altered by endotoxin treatment, whereas in tumour-bearing rats a number of biochemical parameters that were initially perturbed by the presence of the tumour had returned to normal at 48 h post-treatment. The beneficial effects included increased blood glucose and insulin concentrations, and decreased ketone body, triglyceride and lactate concentrations. Potentially non-beneficial effects of endotoxin observed in both tumour-bearing and control rats included decreased plasma cholesterol, and increased plasma phosphate, potassium and alkaline phosphatase levels. Endotoxin caused haemorrhaging in the encapsulated tumour, and this was associated with histological evidence of endothelial damage, red cell infiltration into surrounding tumour tissue and a marked decrease in cell viability. The in vivo uptake of glucose by the tumour, measured by 2-deoxy [U-14C]glucose uptake, was decreased by 96% following endotoxin treatment, and this was associated with a two-fold increase in glucose uptake by muscle. It is concluded that endotoxin treatment has major effects on cell viability and the integrity of vasculature in the tumour, which limits glucose uptake by the tumour and thereby decreases the energy and substrate requirements of the tumour, thus benefiting the host. It is suggested that tumour cytotoxicity and intra-tumour haemorrhage are the result of endotoxin stimulating cytokine release from macrophages that are already activated by the presence of the tumour.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1992

Hemoglobin A1c by HPLC with the Pharmacia Mono S HR 5/N cation-exchange column: influence of sample protein load on optimal chromatographic conditions.

The Pharmacia Mono S HR 5/5 column has been optimized for hemoglobin A1c analysis by HPLC by using a much smaller column load, decreased buffer flow rate, and a steeper gradient than was used in previously described methods. Superior chromatographic separation, shorter analysis time, and a greatly extended column life have resulted.

Cations↗

PubMed1992

Determinants of synovial fluid lactate concentration.

The resting intraarticular pressure and the type of arthropathy [rheumatoid arthritis (RA) or non-RA] have been examined for their importance as determinants of synovial fluid (SF) lactate concentration in patients with knee effusions. SF lactate concentration was higher in RA than in non-RA knees. This difference was not related to the resting intraarticular pressure at the time of sampling. After drainage of SF and saline lavage of the joint, the rate of increase of lactate in a fixed volume of intraarticular saline was examined under resting conditions. The rate of increase of the lactate concentration was significantly greater in RA joints. It is most likely that SF lactate concentration under resting conditions will reflect the lactate concentration during the preceding period of activity which, in turn, is probably a composite function of the extent of synovial hypoxia due to hypoperfusion and the type of arthropathy.

Arthritis, Rheumatoid↗

PubMed1991

The inhibition of metabolic oxalate production by sulfhydryl compounds.

A number of sulfhydryl compounds were shown to inhibit CO2 and oxalate formation from glyoxylate by rat liver homogenates and hepatocytes. The most significant inhibition occurred with cysteine and this inhibition was concentration-dependent. In rats made hyperoxaluric by administering ethylene glycol in their drinking water, daily intraperitoneal injections of cysteine caused a rapid and marked decrease in urinary oxalate excretion which was maintained over the duration of the treatment (28 days). Over this time period, the level of urinary oxalate excretion in these ethylene glycol-treated rats was reduced to that of the controls. It is postulated that the decrease is due to the formation of a cysteine-glyoxylate adduct, 2-carboxy-4-thiazolidine carboxylate, which prevents glyoxylate being further oxidized to oxalate. Cysteine or similar sulphydryl compounds may therefore have potential as therapeutic agents in the prevention of renal stones.

Aluminum↗

PubMed1991

Investigations into the effect of glyoxylate decarboxylation and transamination on oxalate formation in the rat.

The decarboxylation and transamination reactions of glyoxylate, which divert this precursor from oxalate formation, have been investigated. Decarboxylation of glyoxylate is synergistic with 2-oxoglutarate and catalysed by 2-oxoglutarate:glyoxylate carboligase which co-chromatographs with the 2-oxoglutarate dehydrogenase complex. The activity is located in the mitochondrial fraction and is probably due to the E1 subunit of the complex. A greater amount of decarboxylation occurs from 2-oxoglutarate than from glyoxylate but the presence of 2-oxoglutarate does not affect oxalate formation from glyoxylate. There is no oxalate formation from 2-oxoglutarate. Studies with rat liver homogenates showed that a number of amino acids can participate in glyoxylate transamination. However, using isolated rat hepatocytes, these reactions did not have a significant effect on oxalate formation from glyoxylate with the exception of cysteine which caused an 80% reduction in oxalate formation. Investigation of this inhibition indicated that it was most likely due to the formation of a cysteine-glyoxylate adduct which makes glyoxylate unavailable for oxidation to oxalate. This cysteine inhibition of oxalate formation was also demonstrated in normal rats and rats made hyperoxaluric by injecting them with either glyoxylate or glycolate. The results indicate that sulphydryl compounds, which can have a therapeutic role as oxalate-lowering agents, may be able to be developed.

Aldehyde-Ketone Transferases↗

PubMed1990

Biochemical manifestations of a rat mammary adenocarcinoma-producing cachexia: in vivo and in vitro studies.

The physical and metabolic characteristics of a Dark Agouti rat mammary adenocarcinoma and its effects on host metabolism are described. The tumour was characterized by a lack of glandular differentiation, tetraploidy, a rapid mitotic index and a high rate of glycolysis. The adenocarcinoma was readily maintained in tissue culture and could be passaged through the host by inoculating either cell suspensions or tissue explants. In the rat, tumour growth resulted in a loss of adipose tissue at a tumour mass of less than 5% body weight indicating that increased energy expenditure was already present at that stage. In addition the tumour caused anaemia, hypercalcaemia and hypoglycaemia. Hyperketonaemia was also observed in fasted tumour-bearing rats. Methotrexate arrested tumour growth in vivo. These aspects of the tumour model make it useful for investigations into host-tumour competition and mechanisms of cachexia.

Adenocarcinoma↗

PubMed1990

Prevention of adjuvant-induced cachexia in rats by cyclosporin A.

The changes in food intake and biochemistry following Freund's adjuvant (AJ)-induced inflammation in rats were investigated. Injection of AJ into rats resulted in a transient anorexia but a sustained decrease in body weight. Within 14 days, body weight decreased by 12% (P less than 0.05) and adipose tissue (retroperitoneal fat pads) decreased by more than 50%. Biochemical changes seen in association with the AJ-induced wasting included decreased plasma concentrations of triglyceride and cholesterol. Injection of cyclosporin-A (CS) (20 mg/kg) with the AJ decreased the anorexia, prevented the sustained loss of body weight and adipose tissue and reversed the effects on plasma triglyceride and cholesterol concentrations. Insulin concentrations were not significantly affected by the AJ or AJ/CS treatments. Peritoneal macrophages from AJ-treated rats produced 3-fold more tumour necrosis factor-alpha (cachectin) than control rats. This effect was not observed in rats treated with AJ plus CS. The results are consistent with CS preventing the release of cytokines which have anorectic and catabolic actions (IL-1, TNF), although there is also the possibility that CS has effects involving endocrine mechanisms.

Adipose Tissue↗

PubMed1990

Intraarticular pressure and the relationship between synovial perfusion and metabolic demand.

We examined the influence of intraarticular pressure on products of synovial energy metabolism in patients with knee effusions. A range of intraarticular pressures was generated by controlled flexion. Pressures greater than or equal to 45 mm Hg were associated with increased synovial fluid lactate concentrations and pCO2, and decreased pH. Our results suggest that pressures greater than or equal to 45 mm Hg, which we also observed during standing and walking, can cause synovial ischemia and hypoxia manifest in a perfusion/metabolic demand mismatch. Monitoring changes in SF concentrations of uric acid did not provide consistent evidence for accelerated purine degradation following periods of inadequate perfusion. Overall, our results suggest that synovial blood flow can be compromised by modest elevations in intraarticular pressure in the range encountered during daily activity in patients with knee effusions.

Adult↗