Serum ferritin/C-reactive protein ratio is a simple and effective biomarker for diagnosing iron deficiency in the context of systemic inflammation.

BACKGROUND: Diagnosing iron deficiency is challenging in the presence of systemic inflammation. AIM: To investigate the relationship between plasma C-reactive protein (CRP), serum ferritin (SF) and transferrin saturation (TS), with the objective of establishing a straightforward ratio applicable in the presence of inflammatory syndrome. DESIGN: Test prospective cohort and validation retrospective cohort. METHODS: A prospective cohort of inpatients (n = 140) assessed the correlation between CRP and SF/TS levels. The diagnostic performance of a determined ratio was evaluated for identifying iron deficiency (ID) using different definitions and in the presence of inflammation and/or chronic heart and/or kidney failure. A large validation cohort (n = 795) further assessed the predictive power of this ratio. RESULTS: In a training cohort (median age 76 years [57-84]), a linear relation was observed between SF (µg/l) and CRP (mg/l), unlike with TS. The SF/CRP ratio accurately predicted ID, with receiver operating characteristic-area under the curve (ROC-AUC) values ranging from 0.85 to 0.92 for different ID definitions. A threshold of ≤6 demonstrated the highest Youden index (0.61). In the validation cohort (age 72 years [57-84]), the SF/CRP ratio exhibited an ROC-AUC of 0.88 [95% CI: 0.85-0.90], with an odds ratio of 37.9 [95% CI: 20.3-68.9] for the threshold of ≤6. CONCLUSION: In this study, we demonstrated that the SF/CRP ratio, with a threshold of ≤6, is a simple and effective biomarker for ID, even in the presence of systemic inflammation or comorbidities. This ratio could potentially replace the complex set of criteria currently recommended by learned societies.

Influence of the type of training sport practised on psychological and physiological parameters during exhausting endurance exercises.

The present purpose was to study the influence of the type of training sport practised (long distance running, sprinting, handball) on ratings of perceived exertion (RPE), estimation of time limit (ETL), and heart rate (HR) on running tests. It was hypothesised that these parameters would be related to the type of training sport practised. 31 trained women (10 endurance-trained runners, 10 sprinters, and 11 handball players) performed two exercises to exhaustion on an outdoor track. The first test was a graded run to estimate maximal aerobic speed (SMA), i.e., the minimal speed which elicited maximal oxygen uptake. The second test was a constant all-out run at speed delta 50 (Sdelta50), which corresponded to the speed halfway between SMA and the speed at lactate threshold (SLT), to specify time to exhaustion at this intensity (TLIM). Sensations regarding RPE, ETL, and HR were recorded during these tests. SMA, Sdelta50, and SLT, expressed in absolute values (km x hr.(-1)) were statistically significantly different between groups (p < .05) whereas TLIM was not. The covariance analysis showed that endurance-trained runners perceived the exercise as lighter and presented lower HR than handball players and sprinters for a same running %SMA (p < .05). Moreover, endurance-trained runners felt that they could endure more than the other groups at a given %SMA or relative exhaustion time (%TLIM). These results mean that the type of training sport which has been performed may mediate perceptual responses and influence physiological parameters during exhausting exercises. These results are likely in part related to sport-specificity of the exercise mode used in tests. This point must be taken into consideration by physical trainers who have to prescribe exercise intensities during athletic seasons for different groups of athletes.

Diurnal variations in insulin secretion and K+ permeability in isolated rat islets.

1. The effects of glucose on insulin secretion and 86Rb efflux from isolated rat islets were studied at six different times during a 24-h period (00.00, 04.00, 08.00, 12.00, 16.00 and 20.00 h). 2. In the absence of glucose and in the presence of substimulatory concentrations (2.8 mmol/L) of the sugar, insulin secretion did not vary with the time of day. At a glucose concentration of 5.6 mmol/L the stimulated insulin secretion was greater than basal levels only at 20.00 h. 3. At a higher sugar concentration (8.3 mmol/L) the increase in insulin secretion and the reduction in 86Rb efflux rate were more marked during the dark period. No effect of the time of day on insulin secretion was observed at glucose concentrations above 8.3 mmol/L (except in 27.7 mmol/L). 4. The time of day appears to affect insulin secretion mainly at glucose concentrations close to physiological values (5.6-8.3 mmol/L). 5. This result agrees with the ability of physiological amounts of glucose to alter the 86Rb-permeability of pancreatic B cells at the same time intervals.

Effect of chemical stimulation of the dorsomedial hypothalamic nucleus on blood plasma glucose, triglycerides and free fatty acids in rats.

The effects of chemical stimulation of the dorsomedial hypothalamic nucleus (DMH) on blood plasma concentration of glucose, triglycerides, insulin, and free fatty acids (FFA) were investigated in anesthetized adult Wistar rats. Microinjection of 12.5 nmol of norepinephrine into the DMH increased blood plasma concentration of glucose and FFA, decreased triglycerides, and did not change plasma insulin within 5 min; after 20 min, blood glucose and FFA reached control values. Microinjection of epinephrine (12.5 nmol) into the DMH also increased blood plasma glucose concentration and decreased triglycerides after 5 min. These effects are probably mediated by beta-adrenergic mechanisms, because they were prevented by beta-adrenergic antagonist propranolol, but not by alpha-adrenergic antagonist prazosin. Microinjection into the DMH of glutamate, dopamine, or acetylcholine failed to cause any change in those metabolic parameters, corroborating the hypothesis that the DMH is part of a beta-adrenergic pathway involved in short-term modulation of the availability of glucose and FFA.

Prolactin induces maturation of glucose sensing mechanisms in cultured neonatal rat islets.

The effects of PRL treatment on insulin content and secretion, and 86Rb and 45Ca fluxes from neonatal rat islets maintained in culture for 7-9 days were studied. PRL treatment enhanced islet insulin content by 40% and enhanced early insulin secretion evoked by 16.7 mM glucose. Insulin release stimulated by oxotremorine-M, a muscarinic agonist, in the presence of glucose (8.3 or 16.7 mM) was unchanged by PRL treatment. However, PRL treatment potentiated phorbol 12,13-dibutyrate-stimulated insulin secretion in the presence of the above glucose concentrations. PRL treatment potentiated the reduction in 86Rb efflux induced by glucose or tolbutamide and enhanced the increase in 86Rb efflux evoked by diazoxide. PRL treatment slightly potentiated the increment in 45Ca uptake induced by high concentrations of K+, but failed to affect the increment evoked by 16.7 mM glucose. Since glucose-induced 45Ca uptake was not affected by PRL, we suggest that the enhancement in first phase insulin secretion evoked by glucose in the PRL-treated islets occurs at a step in the secretory process that may involve protein kinase-C. These data further support observations that PRL treatment increases islet sensitivity to glucose.

Inhibition of insulin release by Jatrophone.

In many countries, including Brazil, extracts of Jatrophona elliptica species are currently used for the treatment of several diseases. Recently it was shown that a purified compound from these plants inhibits contraction of smooth and cardiac muscle in the microM range, probably involving alterations in membrane Ca2+ permeability and/or internal Ca2+ distribution. In collagenase-isolated rat islets and in the absence of glucose, basal insulin secretion measured by radioimmunoassay averaged 122 +/- 13 microU/islet per 90 min (N = 25). At 16.7 mM glucose, the insulin output reached 445 +/- 32 microU/islet per 90 min (N = 27). Jatrophone (1-100 microM/l) caused a dose-related inhibition of glucose-induced insulin release, over basal secretion, with an ID50 close to 8 microM/l. Complete inhibition of insulin release was obtained with 100 microM/l Jatrophone. However, at 100 microM/l (but not at 10 microM/l) concentration, Jatrophone also provoked a reduction in glucose metabolism by the islets which could explain, at least in part, the reduction in insulin secretion. After 120-min incubation, the glucose metabolism, measured by the 14CO2 production, was reduced from 26.58 +/- 3.63 (N = 42) to 7.48 +/- 1.36 (N = 16) pmol/l per islet. In conclusion, at lower concentrations (10 microM/l) Jatrophone could be a valuable tool for the study of the mechanism of insulin release induced either by glucose or other secretagogues.

Inhibition of insulin release by jatrophone

In may countries, including Brazil, extracts of Jatrophona elliptica species are currently used for the treatment of several diseases. Recently it was shown that a purified compound from these plants inhibits contraction of smooth and cardiac muscle in the uM range, probably involving alterations membrane Ca2+ permeability and/or internal Ca2+ distribution. In the collagenase-isolated rat islets and in the absence of glucose, basal insulin secretion measured by radioimmunoassay averaged 122 ñ 13 uU/islet per 90 min (N=27). Jatrophone (1-100 uM/l) caused a dose-related inhibition of glucose-induced insulin release, over basal secretion, with an ID50 close to 8 uM/l. Complete inhibition of insulin release was obtained with 100 uM/l Jatrophone. However, at 100 uM/l (but not at 10 uM/l) concentration, Jatrophone also provoked a reduction in glucose metabolism by the islets which could explain, at least in part, the reduction in insulin secretion. After 120-min incubation,. the glucose metabolism, measured by the 14CO2 production, was reduced from 26.58 ñ 3.63 (N=42) to 7.48 ñ 1.36 (N=16) pmol/l per islet. In conclusion at lower concentrations (10 uM/l) Jatrophone could be a valuable tool for the study of the mechanism of insulin release induced either by glucose or other secretagogues

A time-course study of physiological indicators of handling stress in the tropical fish Piaractus mesopotamicus (pacu).

The response of juvenile cultivated Piaractus mesopotamicus to handling stress, without anesthesia, was determined over 3-5 min (T1), 1 h (T2) and 6 h (T3) after capture. Plasma cortisol, glucose and total cholesterol were measured. Hyperglycemia present at T2 continued to rise until T3 while plasma cortisol levels increased but were similar at T2 and T3. Total plasma cholesterol was altered only at T3. Hyperglycemic changes were greater in fish without than with stomach contents during the T2-T3 period. These differences in hyperglycemic changes may reflect the role of hormones other than cortisol in the regulation of glucose release in these fish.

A time-course study of physiological indicators of handling stress in the tropical fish Piaractus mesopotamicus (Pacu)

The response of hjuvenile cultivated piaractus mesopotamicus to handling stress, without anesthesia, was determined over 3-5 min (T1), 1H(T2) and 6h(T3) after capture. Plasma cortisol, glucose and total cholesterol were measured. Hyperglicemia present at T2 continued to rise until T3 while plasma cortisol levels increased but were similar at T2 and T3. Total plasma cholesterol was altered only at T3. Hyperglycemic changes were greater in fish without than with stomach contents during the T2-T3 period. these differences in hyperglycemic changes may reflect the role ogf hormones other than cortisol in the regulation of glucose release in these fish

Cation transport by pancreatic beta-cells: effect of 4-aminopyridine on 86Rb+ and 45Ca2+ fluxes.

The effects of 4-aminopyridine (4-AP) on insulin release, glucose oxidation and 86Rb+ and 45Ca2+ fluxes of rat isolated islets were studied. 4-AP (0.1 and 1.0 mM) did not alter the 86Rb+ fractional efflux. However, 10 mM 4-AP significantly increased the 86Rb+ fractional efflux. 10 mM 4-AP also reduced the insulin release from islets incubated over 90 min in the presence of both 6 and 16.7 mM glucose and from perifused islet in the presence of 16.7 mM glucose. 4-AP (10 mM) only transiently increased the insulin release and the 45Ca2+ fractional efflux in the presence of 6 mM glucose. The 45Ca2+ fractional efflux was not changed when the islets were perifused at higher glucose concentration. At zero, 6 or 16.7 mM glucose, 4-AP (10 mM) significantly increased the 45Ca2+ net uptake by islets incubated for 90 min. 10 mM 4-AP significantly reduced the glucose oxidation of islets incubated for 120 min in the presence of 16.7 mM glucose. The effects of 10 mM 4-AP on the dynamics of insulin release and 86Rb+ fractional efflux were poorly reversible. In conclusion, 4-AP, at concentrations that did not alter the glucose metabolism, (0.1 and 1 mM), failed to affect the K+ permeability in beta-cells as judged by the measurements of 86Rb+ fractional efflux. At higher concentrations (10 mM) 4-AP increased 86Rb+ efflux, decreased glucose metabolism and reduced insulin release.

The mechanism of gentamicin-inhibited insulin release by isolated islets.

These experiments were performed in order to determine the mechanism of action of the aminoglycoside antibiotic gentamicin on insulin release by isolated islets. Gentamicin significantly reduced the insulin release in the absence as well as in the presence of increasing concentrations of glucose. This effect was immediate and promptly reversible. In the presence of glucose plus high concentrations of K+ the antibiotic did not affect insulin secretion. Gentamicin did not change 86Rb efflux from perifused islets or the glucose metabolism in incubated islets. These data show that gentamicin does not alter the recognition and subsequent metabolism of glucose, and the system responsible for insulin secretion. We suggest that gentamicin reduces glucose-induced insulin release by blocking the entry of Ca2+ into the B-cells.