Under-vaccinated groups in Europe and their beliefs, attitudes and reasons for non-vaccination; two systematic reviews.

BACKGROUND: Despite effective national immunisation programmes in Europe, some groups remain incompletely or un-vaccinated ('under-vaccinated'), with underserved minorities and certain religious/ideological groups repeatedly being involved in outbreaks of vaccine preventable diseases (VPD). Gaining insight into factors regarding acceptance of vaccination of 'under-vaccinated groups' (UVGs) might give opportunities to communicate with them in a trusty and reliable manner that respects their belief system and that, maybe, increase vaccination uptake. We aimed to identify and describe UVGs in Europe and to describe beliefs, attitudes and reasons for non-vaccination in the identified UVGs. METHODS: We defined a UVG as a group of persons who share the same beliefs and/or live in socially close-knit communities in Europe and who have/had historically low vaccination coverage and/or experienced outbreaks of VPDs since 1950. We searched MEDLINE, EMBASE and PsycINFO databases using specific search term combinations. For the first systematic review, studies that described a group in Europe with an outbreak or low vaccination coverage for a VPD were selected and for the second systematic review, studies that described possible factors that are associated with non-vaccination in these groups were selected. RESULTS: We selected 48 articles out of 606 and 13 articles out of 406 from the first and second search, respectively. Five UVGs were identified in the literature: Orthodox Protestant communities, Anthroposophists, Roma, Irish Travellers, and Orthodox Jewish communities. The main reported factors regarding vaccination were perceived non-severity of traditional "childhood" diseases, fear of vaccine side-effects, and need for more information about for example risk of vaccination. CONCLUSIONS: Within each UVG identified, there are a variety of health beliefs and objections to vaccination. In addition, similar factors are shared by several of these groups. Communication strategies regarding these similar factors such as educating people about the risks associated with being vaccinated versus not being vaccinated, addressing their concerns, and countering vaccination myths present among members of a specific UVG through a trusted source, can establish a reliable relationship with these groups and increase their vaccination uptake. Furthermore, other interventions such as improving access to health care could certainly increase vaccination uptake in Roma and Irish travellers.

Microbial interventions are an easier alternative to engineer higher organisms.

Advances in synthetic biology have made microbes easier to engineer than ever before. However, synthetic biology in animals and plants has lagged behind. Since it is now known that the phenotype of higher organisms depends largely on their microbiota, we propose that this is an easier route to achieving synthetic biology applications in these organisms.

Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study.

BACKGROUND: Adequate indication and duration of administration are central issues of modern antibiotic treatment in intensive care medicine. The biochemical variable procalcitonin (PCT) is known to indicate systemically relevant bacterial infections with high accuracy. In the present study, we aimed to investigate the clinical usefulness of PCT for guiding antibiotic treatment in surgical intensive care patients with severe sepsis. PATIENTS AND METHODS: Patients were randomly assigned to a PCT-guided or a control group requiring antibiotic treatment. All patients received a calculated antibiotic regimen according to the presumed microbiological spectrum. In the PCT-guided group, antibiotic treatment was discontinued if clinical signs of infection improved and the PCT value was either <1 ng/ml or decreased to <35% of the initial concentration within three consecutive days. In the control group, antibiotic treatment was directed by empirical rules. RESULTS: The PCT-guided group (n = 14 patients) and the control group (n = 13 patients) did not differ in terms of biological variables, underlying diseases, and overall disease severity. PCT guidance led to a significant reduction of antibiotic treatment from 6.6 +/- 1.1 days (mean +/- SD) compared with 8.3 +/- 0.7 days in control patients (p < 0.001) along with a reduction of antibiotic treatment costs of 17.8% (p < 0.01) without any adverse effects on outcome. CONCLUSIONS: Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients with severe sepsis. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistances and costs in intensive care medicine.

[Antibiotic treatment of surgical intensive care patients: procalcitonin to guide duration of therapy]. / Antibiotikatherapie bei operativen Intensivpatienten: Prokalzitonin zur Steuerung der Therapiedauer.

The development of resistance by infective bacterial species is an incentive to reconsider the indications and administration of available antibiotics. Correct recognition of the indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care situation. There has as yet been no clinical chemical parameter which is capable of specifically distinguishing a bacterial infection from a viral or non-infectious inflammatory reaction, but it now appears that procalcitonin (PCT) offers this possibility. The present study was intended to clarify whether PCT can be used to guide antibiotic therapy in surgical intensive care patients. A total of 110 patients in a surgical intensive care ward receiving antibiotic therapy after confirmed infection or a high grade suspicion of infection were enrolled in this study. In 57 of these patients a new decision was reached each day as to whether the antibiotic therapy should be continued after daily PCT determination and clinical assessment. The control group consisted of 53 patients with a standardized duration of antibiotic therapy over 8 days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter compared to controls (5.9+/-1.7 vs. 7.9+/-0.5 days, p<0.001) without unfavorable effects on clinical outcome.

Detection of temperature increases in the operating range of warm receptors and of nociceptors.

In healthy subjects the ability to detect small temperature increases in a 'two-alternative forced choice' experiment was tested from different basic temperatures ranging between 36 and 46 degrees C. Detection improved up to an adapting temperature (AT) of 40 degrees C, a further increase of AT into the operating range of nociceptors did not change detection rate. In several experiments the subjects have been asked to rate their confidence after each forced choice on a 6-point scale. From these confidence ratings two measures developed in the context of 'Sensory Decision Theory' have been calculated, one of 'discrimination' and one of 'bias.' A bias towards higher confidence in having detected temperature increases was found to be the clearest sign of transition into the operating range of nociceptors.

Changes in metabolism of TRH in euthyroid sick syndrome.

OBJECTIVE: The aim of this study was to examine the metabolism of a simple dose, intravenously administered TRH bolus of 200 microg, in patients with euthyroid sick syndrome (ESS). PATIENTS AND METHODS: A TRH test was performed on ten ESS patients and ten controls upon admission (d1) and after recovery (d2). Blood samples were collected at 0, 10, 20 and 30min after TRH injection. We analyzed the volume of distribution (V(d)), the plasma clearance rate (PCR), the fractional clearance rate (FCR), the half-life (t(1/2)) and the TSH response to the injection of TRH. RESULTS: All patients had lower tri-iodothyronine (T(3)) levels compared with controls (0.9 +/- 0. 1nmol/l vs 1.9 +/- 0.1 nmol/l; P < 0.0001; mean +/- S.D.; paired t-test). In addition, the V(d) (16.7 +/- 5.9/l vs 30.6 +/- 0.6/l; P < 0.0005) and PCR (2.0 +/- 0.80 l/min vs 3.3 +/- 0.25 l/min; P <0. 0005) were found statistically lowered in patients than in controls, whereas FCR (0.119 +/- 0.01 permin vs 0.110 +/- 0.01 per min; P < 0. 025) was found increased in patients as opposed to controls. The t(1/2) of exogenously administered TRH was increased in ESS compared with controls (7.2 +/- 0.7 min vs 6.3 +/- 0.6 min; P <0.005). TSH response to TRH was found significantly repressed at 10, 20 and 30 min after TRH injection. On d2, these findings had reverted to normal and no changes regarding the kinetics of TRH and the response of TSH could be detected between patients and controls. CONCLUSIONS: The results demonstrate an impairment of TRH metabolism in ESS. The findings may suggest altered enzymatic activity, responsible for TRH degradation in states of acute ESS. These changes might be involved in the pathogenesis of ESS and represent part of an adaptive mechanism to this syndrome.

The function of a hydrogen peroxide-detecting electroenzymatic glucose electrode is markedly impaired in human sub-cutaneous tissue and plasma.

Electroenzymatic glucose sensors implanted into sub-cutaneous (s.c.) tissue of human subjects and experimental animals exhibit lower sensitivities to glucose than in buffer solutions before implantation. The mechanism of the decrease of sensitivity is not known. Sensors used in this study were fabricated from platinum wires (diameter 0.125 mm) with covalently bound glucose oxidase at the tip of the wire. After coating the tip with polyurethane, wires were placed into 27 gauge steel needles. Sensors were operated potentiostatically at 700 mV against Ag/AgCl pseudo-reference electrodes. These sensors were implanted s.c. in 6 diabetic patients for 7 h. In 4 patients, sensors were responsive to successive increases of plasma glucose levels. Mean sensitivity to glucose in s.c. tissue was 29% of in vitro sensitivity. In 2 patients there was a sudden decrease of sensor currents, unrelated to glucose, shortly after implantation. Sensors were inhibited in human plasma to a similar extent. When sensors were exposed to native plasma and to plasma ultrafiltrate (mol. wt. < 10 kDa) for 10 h, identical decreases of signals were found. Exposure to dialysed plasma (mol. wt. > 12 kDa) caused much less decrease of sensor signals. Losses of sensor sensitivities to glucose in s.c. tissue and in plasma were totally reversible upon re-exposure of sensors to buffer solutions. We conclude that sensor inactivation in plasma and possibly in s.c. tissue is caused by low molecular weight substances not retained by the polyurethane membrane.

Serum angiotensin-converting enzyme activity and active renin plasma concentrations in insulin-dependent diabetes mellitus.

We report here the alterations of serum angiotensin-converting enzyme activity (S-ACE) and of active renin plasma concentrations (ARPC) in 41 insulin-dependent diabetes mellitus (IDDM) patients compared with those of 26 control subjects. The IDDM patients had S-ACE activity (54 +/- 16 I.E.) in the upper normal range (controls, 39 +/- 7). When the patients were subclassified according to their diabetic complications, a significant increase of S-ACE within the IDDM group compared to the controls was observed in patients with nephropathy (68 +/- 13, P less than 0.001) with persistent proteinuria and with retinopathy (63 +/- 14, P less than 0.001). A significant correlation was found between proteinuria and S-ACE (r = 0.98, P less than 0.001) and between retinopathy and S-ACE levels (r = 64, P less than 0.001). No correlation between blood pressure and S-ACE or between blood glucose and S-ACE was observed. The ARPC were within the normal range in the IDDM (21 +/- 9 ng/l) and in control (19 +/- 3) groups. No correlations between ARPC and blood pressure or blood glucose or the degree of diabetic complications were registered. These data show that S-ACE activity is elevated in IDDM patients with nephropathy-proteinuria and/or with retinopathy and the circulating renin may not represent the renal renin-angiotensin vascular system.

Differential effects of dopamine on glucoregulatory hormones in rats.

The effect of dopamine at different doses on serum concentrations of insulin, glucose and corticosterone and on plasma glucagon concentration was investigated in rats. Dopamine was given intravenously over 6 h with infusion rates of 2.5, 7.5, 15, and 60 micrograms/kg.min and in combination with phentolamine. Serum insulin concentration was unchanged at low doses of dopamine. It was significantly increased from 6.0 +/- 0.7 ng/ml to 13.7 +/- 2.3 ng/ml (P less than 0.01) when 7.5 micrograms/kg.min of dopamine were used, whereas it was significantly depressed to 3.96 +/- 0.89 and to 4.0 +/- 0.34 ng/ml (P less than 0.01), respectively, at the high doses of dopamine. This latter effect could be reversed to 6.7 +/- 1.19 ng/ml and inverted to 9.2 +/- 1.7 ng/ml (P less than 0.01) by simultaneously applied phentolamine at appropriate dosages. Serum glucose levels were markedly elevated from 154 +/- 7 to 234 +/- 42 mg/dl (P less than 0.01) by the higher doses of dopamine. A significant alteration of glucagon plasma concentrations from 18.9 +/- 2.8 to 42.3 +/- 14 pg/ml (P less than 0.01) was elicited only by 7.5 micrograms/kg.min of dopamine. The data clearly demonstrate that exogenous dopamine acts differently on glucose homeostasis according to the dosage. The study provides strong evidence that dopamine decreases insulin levels via alpha-adrenergic receptor stimulation. This effect may contribute to the deterioration of glucose homeostasis with high doses of dopamine.

Thyrotropin-releasing hormone: pharmacokinetic and pharmacodynamic properties in chronic renal failure.

The pharmacokinetics of thyrotropin-releasing hormone (TRH) were determined following a single i.v. administration in ten patients with chronic renal failure (CRF) maintained on chronic hemodialysis and in six normal subjects. A TRH-test (200 micrograms) was performed in all subjects on nondialysis days and was followed by sequential venous blood sampling at 0, 2, 5, 10, 20, 30 and 60 min. Plasma TRH and serum concentrations of TSH, T4, FT4 and T3 were measured by specific and sensitive RIA's. Serum thyroid hormone concentrations were lower in the hemodialysis patients than in the normals (p < 0.001). Basal TRH and TSH levels were similar in patients and in controls, however, a blunted response of TSH to TRH in CRF (3.8 +/- 2.4 vs. 11.2 +/- 2.6 mU/l, p < 0.001) was observed. Mean peak TRH concentrations (Cmax) were 34.445 (11.085, SD) fmoles/ml in CRF and only (13,400 (1.020) in the normals 2 min after TRH administration (tmax). The mean elimination half-life (t1/2) of TRH was 16 min in CRF and 6.5 min in normals (p < 0.001). The metabolic clearance rate (MCR) was markedly lowered in CRF, 58.3 (19.1) compared to normals (82.2 [15.3] l/m2/day, p < 0.001). The area under the plasma concentration-time curve (AUC) was 57.529 (28.562) fmoles.ml-1.min in CRF and 37.339 (5.026) (p < 0.005) in normals. These findings indicate that the pharmacokinetic properties of TRH are impaired in CRF. The kidney might be an important catabolic organ for exogenous TRH. Dosing schedules of TRH require possible adaptation to renal function.

The first experimental diabetes mellitus.

In the history of diabetes research, surgically induced experimental diabetes is usually associated with the names of Minkowski and von Mering on the basis of their investigations in 1889. However, temporary diabetes mellitus had already been induced 200 years previously by Johann Conrad Brunner (1653-1727) in an experiment in dogs. According to present-day knowledge, this temporary diabetes mellitus must be ascribed to subtotal pancreatectomy and reversible traumatic damage to the remaining endocrine pancreas. The brilliant experimenter Brunner did not associate the symptoms he produced with diabetes. Diabetes research would possibly have taken a different course had he done so.

Peripheral autoregulation of thyromimetic activity in man.

This study describes an extrathyroidal mechanism for regulating serum concentration of triiodothyronine (T3) in thyroxine (T4) deficiency or excess. Serum levels of T3, T4, reverse T3 (rT3), and thyrotropin were determined in two series of athyreotic patients (n = 22 and n = 16, respectively) during various doses of T4 substitution therapy. The patients were followed from the severe hypothyroid state up to the modest hyperthyroid state, induced by stepwise increasing doses of administered T4. The periods of constant T4 replacement doses were 1 week (group I) and 5 weeks (group II), respectively. As serum T4 levels rose from less than 0.5 micrograms/dl to 18.9 micrograms/dl, serum T3 levels showed a curvilinear increase, which was pronounced in the very low T4 range while it was flattened at the higher end of the spectrum of T4 levels. As to rT3, an analogous course did not occur. The different character of the relationships between T4 and its conversion products was further elucidated by calculating the T3/T4 and rT3/T4 ratios. T3/T4 ratio declined fourfold from 43.3.10(-3) in the severe hypothyroid to 11.7.10(-3) in the hyperthyroid range. The results support the hypothesis of a peripheral autoregulation of T4 to T3 conversion which appears to be operative at both ends of the T4 spectrum and which serves to maintain or defend serum T3 levels.

Thyroxine and reverse T3 5'deiodination in the cells of human adipose tissue.

The intracellular 5'deiodination (5'D) of T4 and rT3 has been investigated in human adipose tissue. We studied 5'D in intact adipose tissue, its morphological components and in 3T3-L1-cells. 5'D as assessed by T3-production out of T4 and by rT3-decomposition was not inhibited by propylthiouracil (PTU), but by iopodate (IOP). The apparent Michaelis constants were kM = 3 nM for rT3 and kM = 1 microM for T4. The rT3-degradation was linear over 25 h (115 pg/h.mg (prot.)) both at 37 degrees C and at 4 degrees C. The same type of 5'D was observed in adipocytes, stromal-vascular cells and in 3T3-L1-cells regarding T4 to T3 degradation (244 +/- 30, 181 +/- 27, 227 +/- 37 pg T3/mg.min), resp.; PTU did not exert any influence upon 5'D in the cells investigated. We conclude, that i. the intracellular generation of T3 in adipose tissue does not derive from type I deiodination; ii. 5'D in adipocyte precursors and differentiated adipocytes is identical and iii. there is no difference between human cells and 3T3-L1-cells regarding 5'D.

[Reliability of perfusion manometry in the gastro-esophageal closure mechanism (author's transl)]. / Die Messgenauigkeit der Durchzugs-Perfusionsmanometrie im gastroösophagealen Verschluss.

Manometric investigation of the gastro-esophageal closure mechanism is an important tool for the classification and adequate therapy of functional disorders in this region. Because of the relatively low pressure differences the reliability of a measuring procedure has to meet all requirements. Manometry by continuously perfused and withdrawn catheters being the most frequently applied measuring procedure got some criticism regarding its reliability and reproducibility. The theoretical basis of this criticism is examined closely. The reproducibility of the recorded pressure curves is studied and quantified in 36 dogs and 122 persons (32 controls, 63 patients with hiatal hernia, 27 patients with achalasia of the cardia). On experimental condition, lower esophagel sphincter pressure shows a high degree of reproducibility (retest reliability r = .98, p less than 0.001), in clinical investigations it is significantly lower (r = .81). There are no statistically significant differences between the patient groups and the controls. The importance of the findings for the reliability and the interpretation of clinical manometric data is discussed.

The influence of circulating thyroxine serum concentration on hepatic thyroxine deiodinating activity in rats.

The influence of varying thyroid metabolic states, induced by thyroxine (T4) application, upon type I T4 deiodinating activity has been assessed in the rat liver. A series of 18 rats was thyroidectomized and treated with T4 at various doses, ranging from 0 to 50 micrograms/kg b.w. Microsomal T4 to triiodothyronine (T3) deiodinating activity (5'DA) and T4 to reverse T3 (rT3) deiodinating activity (5DA) as well as cytosolic non protein bound thiol content (NP-SH) were determined in the liver; concentrations of T4, T3, and rT3 were measured in the serum. In the experimental rats, T4 serum concentrations ranged from 1.3 micrograms/dl to 15.6 micrograms/dl (controls, 5 +/- 0.2 micrograms/dl, mean +/- SEM), T3 varied between 33 ng/dl and 150 ng/dl (91 +/- 3 ng/dl), and rT3 between 2 ng/dl and 25 ng/dl (7 +/- 2 ng/dl). Relating T4 to T3 serum levels, a curvilinear relationship (power function, r = 0.94, p less than 0.001), as described previously in man, was confirmed in the rats, as was the linear relationship between T4 and rT3 serum levels (r = 0.75, p less than 0.001). Individual 5'DA increased by more than fourfold, from 531 pg/mg.min to 2,234 pg/mg.min (controls, 1,419 +/- 67 pg/mg.min), when passing from low to high T4 serum values. The increase in 5'DA was steeper in the low T4 range, while it was progressively flattened under T4 levels above the controls' range. The particular changes in 5'DA can be illustrated by calculating the ratio of 5'DA and T4 serum levels.(ABSTRACT TRUNCATED AT 250 WORDS)

T3-hyperthyroidism caused by enhanced and shifted T4-conversion.

Radioactivities of endogenously labelled thyroid hormones following in vivo application of 131 I and extraction from serial blood samples, show that T4 secretion is enhanced in T3-hyperthyroidism as it is in T4-T3-hyperthyroidism. In an extreme case of T3-hyperthyroidism with serum concentrations (SC) of T3 nearly equal to T4 (1000 ng/dl and 1800 ng/dl, respectively) tracer studies revealed a very short half life of T4 when compared to T3 (21.8 and 20.2 hrs., respectively). In 110 cases with both types of hyperthyroidism, regression analysis showed that T3/T4 ratio as an indicator of T4 conversion, as well as T3/rT3 ratio as an indicator of the direction of the conversion, are related to T4SC (r = -0.84 and -0.72, respectively, p less than 0.001). T3-hyperthyroidism is described by high values of these ratios. For the definition of T3-hyperthyroidism it is suggested that both T4 and rT3SC are within the normal range (T4 less than or equal to 11.5 micrograms/dl, rT3 less than or equal to 43.0 ng/dl) and according to this definition, T3/rT3 is higher than in T4-T3-hyperthyroidism and in an undefined group (24.8 +/- 4.5 vs. 6.3 +/- 0.4 or 7.5 +/- 0.4, respectively). By means of the ratios the undefined group may be allocated to T4-T3-hyperthyroidism. The T3/rT3 ratio is value of greater than 10 has a frequency of 88% in thus defined T3-hyperthyroidism and a ratio of less than or equal to 10 is found in 90% of the other cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid status and hepatic thyroxine deiodinating activity under high-dose long-term nitrendipine.

The influence of high doses of oral nitrendipine on the hypophyseal-thyroid axis and on peripheral thyroxine metabolism was studied in baboons. Administration of 320 mg oral nitrendipine per kg body weight (b.wt.) for three months caused a hypothyroid state with decreased values for thyroxine and reverse triiodothyronine, elevated TSH, but unchanged triiodothyronine; the lower doses investigated (24 and 48 mg/kg b.wt.) were without any effect. High doses of nitrendipine concomitantly increased hepatic 5'-deiodinating activity by a rise in Vmax, which could be attributed to an increase in the deiodinating enzyme content. Normal T3 serum levels in the presence of low T4 serum concentrations under high dose nitrendipine can be ascribed, at least in part, to the enhanced peripheral 5'-deiodination.

Total hip arthroplasty using an uncemented femoral component with taper design: outcome at 10-year follow-up.

The aim of this study was to assess the clinical and radiological outcome of the cementless-system (CLS) femoral component designed by Spotorno with a taper design. Ninety-four patients (107 hips) were operated on from January 1987 to December 1988. The female/male ratio was 2/1, the mean age was 51 years (range 20-77 years). Clinical follow-up was obtained in 89 hips (83%). Five patients (7 hips, 6.5%) could not be traced. Nine patients (11 hips, 10%) had died before the minimum time of follow-up required for this study (10 years). All these hips still had their stem in place at the time of the last intermediate inquiry. The mean follow-up was 10.3 +/- 0.3 years. No stem required revision. According to the Harris score, 84% of hips were rated good or excellent, 14% fair, and 2% poor. The average Harris hip score was 88 at the time of the last follow-up. Fifteen patients (17%) reported occasional thigh pain. All patients reported complete relief of pain within the first 6 months after the operation. Radiologically, 95% of stems showed stable fixation by bony ingrowth, 5% by fibrous ingrowth. Seven (9%) uncemented acetabular components showed progressive migration. Three of those cups had been replaced in the meantime. Fifty-one (65%) of the CLS stems induced either no change in femoral bone density or only patchy loss of bone density localized to zone 1 or 7 according to Gruen, while 27 (35%) of the hips showed some reduction of bone density in the proximal diaphysis of the femur (zone 2 or 6). Severe progressive osteolysis of the femoral cortex underneath the lesser trochanter was found in 4 hips (5%) with coexistent loosening of the cup. In all of these hips, the Mecron cup had been used. At a mean follow-up of 10 years, the results of the CLS femoral component are comparable with those of modern techniques of cementing in primary total hip arthroplasty and with the long-term outcomes of other uncemented stems with tapered design. The long-term fixation of the cup remains an unsolved problem.

Thyroid hormones alter mRNA activity profiles of differentiated 3T3-L1-cells.

The influence of thyroid hormones on the gene expression of 3T3-L1-adipocytes was examined. mRNA activity profiles were investigated by in vitro-translation and 2D-electrophoresis. Seven protein spots out of 210 were sensitive to 3,5,3'-triiodothyronine (T3). All proteins increased from hypothyroid to hyperthyroid status. Additionally two spots increased from hypothyroid to T3-substituted and euthyroid status. There is evidence for the existence of protein S14 in differentiated 3T3-L1-cells, as part of spot 5.

Liver thiol content under varying glucoregulatory states in rats.

The influence of varying glucoregulatory states as induced by fasting, feeding and intravenous glucose infusion on liver thiol content has been assessed in the male rat. As expected, increasing the serum glucose levels from 131 +/- 7 mg/dl to 343 +/- 12 mg/dl (mean +/- S.E.) caused a corresponding increase in serum insulin responses. Rising from 3.2 +/- 0.4 mumol/g w.w. in the fasted group to a peak value of 6.3 +/- 0.4 mumol/g (P less than 0.01) in the group infused by 10% glucose solution, hepatic non protein bound sulphydryl groups (NP-SH) were closely related to serum glucose levels up to 244 +/- 11 mg/dl. When higher glucose doses were infused. NP-SH values fell steadily, they even inclined below the level of the fasted rats after infusion of 30% and 40% glucose solutions (1.3 +/- 0.4 mumol/g w.w., P less than 0.05 and 0.7 +/- 0.3, P less than 0.01, resp.), mean serum glucose levels being 291 +/- 12 and 343 +/- 13 mg/dl, resp. Hepatic protein bound thiols were not affected by any of the glucoregulatory states experimentally induced. The data demonstrate that the glucoregulatory state influences hepatic NP-SH content divergently. The study suggests that under physiological conditions liver NP-SH content covariates positively with serum insulin and glucose levels.