Values In Healthy Control Subjects Research Articles

Evaluation of Serum Amyloid A and some Biochemical markers in Iraqi patients with systemic lupus erythematosus

An autoimmune condition called systemic lupus erythematosus (SLE) is caused by long-term inflammation. Amyloid A (AA) amyloidosis results in nephropathy and other internal symptoms, including death. The current study set out to look at the relationship between serum amyloid A (SAA) levels in circulation and SLE patients. Methods: Sixty SLE patients and 30 healthy with age range (19-55) yearswere involved in this study. A SLE patient wasidentified in the teaching hospital in Baghdad. In this study, laboratory indicators such as blood lipid, kidney function, test results, and total cholesterol (TC), triglyceride (TG), SAA, and ALB were assessed using an automated biochemical analyzer. Results: Patients with active SLE had serum amyloid A (SAA) values 5.83 mg/L [IQR: 2.08–10.87], 4.92 mg/L [IQR: 1.57–11.43], and 1.33 mg/L [IQR: 0.13–3.12], respectively, substantially upper than personswith inactive SLE or healthy control subjects (P < 0.001). ESR values in healthy control subjects, patients with inactive SLE, and patients with active SLE. In conclusion, the current study's findings offered more proof of SAA's potential involvement in SLE and suggested that it might be valuable biomarkers that could reveal more details about the disease's activity.

Current Concept of Quantitative Sensory Testing and Pressure Pain Threshold in Neck/Shoulder and Low Back Pain.

In recent years, several published articles have shown that quantitative sensory testing (QST) and pressure pain threshold (PPT) are useful in the analysis of neck/shoulder and low back pain. A valid reference for normal PPT values might be helpful for the clinical diagnosis of abnormal tenderness or muscle pain. However, there have been no reliable references for PPT values of neck/shoulder and back pain because the data vary depending on the devices used, the measurement units, and the area examined. In this article, we review previously published PPT articles on neck/shoulder and low back pain, discuss the measurement properties of PPT, and summarize the current data on PPT values in patients with chronic pain and healthy volunteers. We also reveal previous issues related to PPT evaluation and discuss the future of PPT assessment for widespread use in general clinics. We outline QST and PPT measurements and what kinds of perceptions can be quantified with the PPT. Ninety-seven articles were selected in the present review, in which we focused on the normative values and abnormal values in volunteers/patients with neck/shoulder and low back pain. We conducted our search of articles using PubMed and Medline, a medical database. We used a combination of “Pressure pain threshold” and “Neck shoulder pain” or “Back pain” as search terms and searched articles from 1 January 2000 to 1 June 2022. From the data extracted, we revealed the PPT values in healthy control subjects and patients with neck/shoulder and low back pain. This database could serve as a benchmark for future research with pressure algometers for the wide use of PPT assessment in clinics.

Differential Effect of Iron and Myelin on Susceptibility MRI in the Substantia Nigra.

Background The heterogeneous composition of substantia nigra (SN), including iron, nigrosome-1 substructure, and myelinated white matter, complicates the interpretation of MRI signals. Purpose To investigate R2* and quantitative susceptibility mapping (QSM) in the SN subdivisions of participants with Parkinson disease and healthy control subjects. Materials and Methods In this prospective study conducted from November 2018 to November 2019, participants with Parkinson disease and sex-matched healthy control subjects underwent 3-T MRI. R2* and QSM values were measured and compared in the anterior SN and posterior SN at the rostral (superior) and caudal (inferior) levels. Postmortem MRI and histology correlation of midbrain tissues was evaluated to investigate the effect of myelin and iron in the SN on R2* and QSM values. Results Forty individuals were evaluated: 20 healthy control subjects (mean age, 61 years ± 3 [standard deviation]; 10 men) and 20 participants with Parkinson disease (mean age, 61 years ± 4; 10 men). The R2* values of participants with Parkinson disease were higher in all subdivisions of the SN compared with R2* values in healthy control subjects (all P < .05). For QSM, no evidence of a difference was found in the rostral posterior SN (healthy control subjects, 54.1 ppb ± 21.0; Parkinson disease, 62.2 ppb ± 19.8; P = .49). The combination of rostral R2* and caudal QSM values resulted in an area under the receiver operating characteristic curve of 0.84. R2* values showed higher correlation with QSM values at the caudal level than at the rostral level within each group (all P < .001). Postmortem investigation demonstrated that R2* and QSM values showed weak correlation in the myelin-rich areas (r = 0.22 and r = 0.36, P < .001) and strong correlation in myelin-scanty areas (r ranged from approximately 0.52 to approximately 0.78, P < .001) in the SN. Conclusion Considering the iron and myelin distribution in the substantia nigra subdivisions, the subdivisional analysis of substantia nigra using R2* and quantitative susceptibility mapping might aid in specifically differentiating individuals with Parkinson disease from healthy control subjects. © RSNA, 2021 Online supplemental material is available for this article.

Short-term resistance training with instability reduces impairment in V wave and H reflex in individuals with Parkinson's disease.

This study had two objectives: 1) to compare the effects of 3 wk of resistance training (RT) and resistance training with instability (RTI) on evoked reflex responses at rest and during maximal voluntary isometric contraction (MVIC) of individuals with Parkinson's disease (PD) and 2) to determine the effectiveness of RT and RTI in moving values of evoked reflex responses of individuals with PD toward values of age-matched healthy control subjects (HCs) (z-score analysis). Ten individuals in the RT group and 10 in the RTI group performed resistance exercises twice a week for 3 wk, but only the RTI group included unstable devices. The HC group (n = 10) were assessed at pretest only. Evoked reflex responses at rest (H reflex and M wave) and during MVIC [supramaximal M-wave amplitude (Msup) and supramaximal V-wave amplitude (Vsup)] of the plantar flexors were assessed before and after the experimental protocol. From pretraining to posttraining, only RTI increased ratio of maximal H-reflex amplitude to maximal M-wave amplitude at rest (Hmax/Mmax), Msup, Vsup/Msup, and peak torque of the plantar flexors (P < 0.05). At posttraining, RTI was more effective than RT in increasing resting Hmax and Vsup and in moving these values to those observed in HCs (P < 0.05). We conclude that short-term RTI is more effective than short-term RT in modulating H-reflex excitability and in increasing efferent neural drive, approaching average values of HCs. Thus short-term RTI may cause positive changes at the spinal and supraspinal levels in individuals with PD. NEW & NOTEWORTHY Maximal H-reflex amplitude (Hmax) at rest and efferent neural drive [i.e., supramaximal V-wave amplitude (Vsup)] to skeletal muscles during maximal contraction are impaired in individuals with Parkinson's disease. Short-term resistance training with instability was more effective than short-term resistance training alone in increasing Hmax and Vsup of individuals with Parkinson's disease, reaching the average values of healthy control subjects.

Isometric knee extension force in Japanese type 2 diabetic patients without apparent diabetic polyneuropathy: Data from the Multicenter Survey of the Isometric Lower Extremity Strength in Type 2 Diabetes study.

Objectives:To determine standard reference values for isometric knee extension force using a cohort of Japanese type 2 diabetic patients without diabetic polyneuropathy.Methods:Patient data were collected from the Multicenter Survey of the Isometric Lower Extremity Strength in Type 2 Diabetes study and compared with previously published data of healthy control subjects. In total, we enrolled 898 patients with type 2 diabetes aged 30–87 years, who did not have diabetic polyneuropathy. The control group included 510 healthy subjects aged 30–88 years. Maximum isometric knee extension force (KEF) values were obtained by using a hand-held dynamometer with belt stabilization. In addition, KEF (kgf) was adjusted for bodyweight (kg) to calculate %KEF.Results:KEF and %KEF decreased with age in both patients with diabetes and healthy control subjects. The mean values of KEF and %KEF in patients with diabetes were reduced by 9.7% and 20.8%, respectively, in males, and by 11.6% and 23.0%, respectively, in females compared to the values in healthy control subjects.Conclusion:KEF and %KEF in patients with type 2 diabetes without diabetic polyneuropathy may reduce by approximately 10% and 20%, respectively, compared to these values in healthy control subjects. This study provides reference values for isometric KEF with respect to sex in a population covering a wide age range.

Evaluation of T1ρ as a potential MR biomarker for liver cirrhosis: Comparison of healthy control subjects and patients with liver cirrhosis

ObjectivesThe purpose of this study was to compare mean liver T1ρ values in patients with liver cirrhosis and healthy control subjects in order to evaluate T1ρ as a potential MR biomarker for liver cirrhosis. Materials and methodsTen healthy control subjects (mean age 42.7 years; 6 female, 4 male) and 21 patients with clinically diagnosed liver cirrhosis (mean age 56.5 years; 5 female, 16 male) were examined at 1.5T (Magnetom Avanto, Siemens). T1ρ-weighted images were acquired using a 2D TurboFLASH sequence (TR/TE 3/1.31ms, FA 8°, FoV 309×380mm, resolution 2×2×6mm, acquisition time 15s, slice thickness 6mm) with spin-lock preparation. T1ρ maps were calculated from five breath-hold measurements, performed with different spin-lock times (4, 8, 16, 32 and 48ms). Mean liver T1ρ values of healthy control subjects and patients with liver cirrhosis were calculated and compared using Student t-test. In addition, a receiver operating characteristic (ROC) curve analysis was performed to evaluate the utility of mean liver T1ρ values for the prediction of liver cirrhosis. ResultsMean liver T1ρ values in patients with liver cirrhosis (57.4±7.4ms) were significantly higher than those of healthy subjects (47.8±4.2ms; p=0.0007). According to the ROC analysis at a threshold value of 50.1ms the sensitivity and specificity of mean liver T1ρ in predicting liver cirrhosis were 90.5% and 90%, respectively. The area under the ROC curve was 0.90. ConclusionMean liver T1ρ values in patients with liver cirrhosis were significantly higher than those in healthy subjects suggesting a potential role of liver T1ρ as a MR biomarker for liver cirrhosis.

Improved Detection of Cardiac Sarcoidosis Using Magnetic Resonance with Myocardial T2 Mapping

Improved Detection of Cardiac Sarcoidosis Using Magnetic Resonance with Myocardial T2 Mapping

Standardizing Nasal Nitric Oxide Measurement as a Test for Primary Ciliary Dyskinesia

Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and interpretation have not been standardized. To use a standard protocol for measuring nNO to establish a disease-specific cutoff value at one site, and then validate at six other sites. At the lead site, nNO was prospectively measured in individuals later confirmed to have PCD by ciliary ultrastructural defects (n = 143) or DNAH11 mutations (n = 6); and in 78 healthy and 146 disease control subjects, including individuals with asthma (n = 37), cystic fibrosis (n = 77), and chronic obstructive pulmonary disease (n = 32). A disease-specific cutoff value was determined, using generalized estimating equations (GEEs). Six other sites prospectively measured nNO in 155 consecutive individuals enrolled for evaluation for possible PCD. At the lead site, nNO values in PCD (mean ± standard deviation, 20.7 ± 24.1 nl/min; range, 1.5-207.3 nl/min) only rarely overlapped with the nNO values of healthy control subjects (304.6 ± 118.8; 125.5-867.0 nl/min), asthma (267.8 ± 103.2; 125.0-589.7 nl/min), or chronic obstructive pulmonary disease (223.7 ± 87.1; 109.7-449.1 nl/min); however, there was overlap with cystic fibrosis (134.0 ± 73.5; 15.6-386.1 nl/min). The disease-specific nNO cutoff value was defined at 77 nl/minute (sensitivity, 0.98; specificity, >0.999). At six other sites, this cutoff identified 70 of the 71 (98.6%) participants with confirmed PCD. Using a standardized protocol in multicenter studies, nNO measurement accurately identifies individuals with PCD, and supports its usefulness as a test to support the clinical diagnosis of PCD.

Examining outcomes from total knee arthroplasty and the relationship between quadriceps strength and knee function over time

Background Temporal-spatial gait parameters improve following total knee arthroplasty (TKA) but lower limb kinematics and moments fail to match those of age-matched healthy individuals. The aim of this study was to determine whether quadriceps strength, clinical measures of knee function, lower limb kinematics, and joint moments improve following arthroplasty and normalize over time. Methods Twelve patients underwent total knee arthroplasty were tested at 3 and 12 months following surgery. Twelve matched controls were also tested. All underwent quadriceps strength testing and gait analysis to calculate knee joint kinematics and kinetics. Function was assessed using clinical tests and self-report. Findings All clinical measures except for quadriceps strength significantly improved from 3 to 12 months. Gait asymmetry was observed at 3 months (lower stance times, peak knee flexion angle, range of motion and vertical ground reaction force), but ankle, knee and hip moments contributing to the total limb support moment were equivalent between legs. At 12 months, gait speed remained significantly slower than controls. Inter-limb differences in peak knee flexion angle and range of motion persisted. Greater hip and lower knee moments were evident in the operated limb, compared to the non-operated limb and controls. Quadriceps strength was positively correlated with faster times on the Time Up and Go and Stair Climbing Test and greater distances during the 6 Minute Walk test. Interpretation Patients who have undergone TKA demonstrate improvements in function as measured by self-report and functional performance measures. Gait becomes more symmetric and quadriceps strength becomes stronger. Some approached the values of healthy control subjects. Important differences still remain however. The larger hip extensor contribution to the total support moment may be to compensate for the diminished knee extensor contribution during level walking. Since instrumented gait analysis and functional performance measures appear to reflect different aspects of recovery following total knee replacement, both should be considered when evaluating gait and function.

Persistent idiopathic facial pain exists independent of somatosensory input from the painful region: findings from quantitative sensory functions and somatotopy of the primary somatosensory cortex

In 14 patients with unilateral persistent idiopathic facial pain (PIFP), classified according to the criteria of the International Headache Society, and 16 age-matched control subjects sensory functions were examined on the face by quantitative sensory testing (QST). Additionally, the somatotopy of the primary somatosensory cortex (SI) to tactile input from the pain area was evaluated by means of magnetoencephalography. Previously reported abnormalities in PIFP as a dishabituation of the R2 component of the blink reflex and psychiatric disturbances were co-evaluated. Psychiatric evaluation included a Structured Clinical Interview for axis-I DSM IV disorders (SCID-I) and employment of the SCL-90-R and a depression scale (ADS). Thresholds to touch, pin prick, warm, cold, heat and pressure pain as well as the pain ratings to single and repetitive (perceptual wind up) painful pin prick stimuli did not indicate a significant sensory deficit or hyperactivity in the pain area when compared with the asymptomatic side nor when compared with the values of healthy control subjects. QST results were not significantly altered in patients ( n=4) that showed an abnormal dishabituation of the R2 component of the blink reflex. The interhemispheric difference in distance between the cortical representation of the lip and the index finger did not differ between patients and control subjects. Psychiatric evaluation did not disclose significant abnormalities at a group level. It is concluded that PIFP is maintained by mechanisms which do not involve somatosensory processing of stimuli from the pain area.

Duration of the P Wave and P Wave Dispersion in Subclinical Hyperthyroidism

To determine whether the values for P wave dispersion (Pdis) and adjusted Pdis, which are simple noninvasive electrocardiographic markers to detect paroxysmal atrial fibrillation, differ in patients with endogenous subclinical hyperthyroidism in comparison with those in healthy control subjects. We measured the maximal P wave duration and the difference between the maximal and the minimal P wave duration (Pdis) from the 12-lead surface electrocardiogram of 36 patients with endogenous subclinical hyperthyroidism and of 22 age- and sex-matched healthy control subjects. Adjusted Pdis (Pdis/square root of the number of measured electrocardiographic leads) was also calculated from each electrocardiogram. The minimal P wave duration was significantly shorter in patients with subclinical hyperthyroidism than in healthy control subjects (P<0.001). Pdis and adjusted Pdis were also significantly higher in the patient group than in the control subjects (P<0.05). By univariate analysis, only thyrotropin levels were found to be associated with adjusted Pdis (r = -0.28; P = 0.03). Pdis and adjusted Pdis differed in patients with endogenous subclinical hyperthyroidism in comparison with those values in healthy control subjects. Thus, these simple electrocardiographic markers may be useful for identifying patients with endogenous subclinical hyperthyroidism who are at risk for paroxysmal atrial fibrillation.

Cerebral blood flow velocity in untreated panic disorder patients: a transcranial doppler ultrasonography study

Background: The aim of this study was to compare resting cerebral blood flow velocity values of unmedicated patients in the acute phase of panic disorder with resting values of healthy control subjects. Methods: Nineteen unmedicated panic disorder patients were assessed for degree of anxiety using the Hamilton Anxiety Scale. The patients and 20 healthy age-matched control subjects were then insonated at rest using transcranial Doppler ultrasonography (TCD). For TCD, the anterior, the middle, and the posterior cerebral arteries were insonated bilaterally in all patients. Results: Compared with healthy age-matched control subjects, acute unmedicated panic disorder patients showed a significant increase in cerebral blood flow velocity, bilaterally in the middle and the anterior cerebral artery, and unilaterally in the left posterior cerebral artery. Cerebral blood flow velocity in the right middle cerebral artery correlated positively to the item “Fear” on the Hamilton Anxiety Scale, whereas pulsatility index in the posterior cerebral artery bilaterally and in the left middle cerebral artery correlated negatively to the item “Mood.” Conclusions: Transcranial Doppler ultrasonography agrees well with validated psychometric methods. If follow-up studies confirm our findings, TCD could allow an objective assessment of the mental state of panic disorder patients and reliably discriminate panic disorder patients from normal control subjects.

Diagnostic Value of Serum IGF-I and IGFBP-3 in Growth Hormone Disorders in Adults

Objective: To investigate the diagnostic value of serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) measurements in adult patients with acromegaly and GH deficiency (GHD). Methods: Serum IGF-I and IGFBP-3 levels were measured in 39 active acromegalic patients, 34 adult patients with GHD and 150 healthy adults. Disease activity in patients with acromegaly was confirmed by nadir GH levels during an oral glucose tolerance test (OGTT). Among patients with acromegaly, 15 had not been treated previously and 24 had been treated but not cured. GHD in adults was diagnosed by an insulin tolerance test (ITT). Among patients with GHD, 15 were aged 20–40 years (9 men and 6 women) and 19 were aged over 40 years (9 men and 10 women). One hundred and fifty healthy subjects were recruited as a control group. To compare the individual serum IGF-I and IGFBP-3 levels of patients with the results of the gold standard, we calculated age- and sex-corrected standard deviation scores (SDS) for individual IGF-I and IGFBP-3 levels. The sensitivities of serum IGF-I and IGFBP-3 measurements for the disease diagnosis were analyzed using the mean ± 2 SD of the values of healthy control subjects as a diagnostic cutoff, defining 95% specificity. Results: The mean IGF-I and IGFBP-3 SDS levels were significantly higher in active acromegalic patients, both untreated and treated but not cured, than in the control subjects (p < 0.05). The sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of acromegaly were 97.4 and 81.8%, respectively. In untreated patients with acromegaly, the sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of disease were 100 and 100%, while these were 95.8 and 72.7% in treated patients with acromegaly. In adult patients with GHD, the mean IGF-I and IGFBP-3 SDS were significantly lower than those of the control subjects (IGF-I, –2.2 ± 0.8 vs. 0.0 ± 1.0 SDS, p < 0.0001); IGFBP-3, –1.7 ± 1.2 vs. 0.0 ± 1.0 SDS, p < 0.0001), but there was a considerable overlap between GHD in adults and the controls. In all patients with GHD, the sensitivities of serum IGF-I and IGFBP-3 measurements were 64.7 and 52.9%, respectively. In the group of women aged 20–40 years, the sensitivity of IGF-I measurement for the diagnosis of GHD was 100%, although the number of patients was only 6. Conclusion: Both serum IGF-I and IGFBP-3 measurements are comparable to an oral glucose tolerance test in patients with untreated acromegaly, but in acromegalic patients that have undergone surgery and/or radiotherapy, serum IGF-I is more valuable for determining disease activity than serum IGFBP-3. Serum IGF-I and IGFBP-3 measurements are not valuable for the diagnosis of GHD in adults, but in women aged 20–40 years serum IGF-I measurement appears to be useful in the diagnosis of GHD.

HMG-CoA Reductase Inhibitors Decrease CD11b Expression and CD11b-Dependent Adhesion of Monocytes to Endothelium and Reduce Increased Adhesiveness of Monocytes Isolated From Patients With Hypercholesterolemia

Objectives. This study sought to determine whether inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase affect CD11b expression and adhesiveness of monocytes in vitro and after treatment of patients with hypercholesterolemia.Background. HMG-CoA reductase inhibitors improve survival of patients with coronary heart disease (CHD) and prevent CHD in hypercholesterolemic men. Because these drugs have been shown to modulate monocyte functions, they may act by reducing monocyte adhesion to endothelium, which is crucial in atherogenesis.Methods. Isolated human blood monocytes were subjected to flow cytometric detection of CD11b and adhesion assays on fixed human endothelial cells after treatment with lovastatin in vitro or ex vivo before and after treatment of hypercholesterolemic patients with HMG-CoA reductase inhibitors.Results. The integrin heterodimer CD11b/CD18 expressed on monocytes interacts with intercellular adhesion molecule-1 on endothelium and is involved in monocyte adhesion to endothelium. Treatment of monocytes with lovastatin in vitro slightly and dose dependently reduced surface expression of CD11b on monocytes. Moreover, lovastatin inhibited CD11b-dependent adhesiveness to fixed endothelium of unstimulated monocytes or monocytes stimulated with monocyte chemotactic protein 1. Coincubation with mevalonate, but not with low density lipoprotein (LDL), reversed the effects of lovastatin, suggesting that early cholesterol precursors, but not cholesterol, are crucial for adhesiveness of CD11b. In hypercholesterolemic patients, adhesion of isolated monocytes to endothelium ex vivo was dramatically increased over values in healthy control subjects. Treatment of these patients with the HMG-CoA reductase inhibitors lovastatin or simvastatin (20 to 40 mg/day) for 6 weeks slightly decreased total and LDL cholesterol plasma levels and monocyte CD11b surface expression but resulted in a significant reduction of monocyte adhesion to endothelium (p < 0.01, n = 7).Conclusions. The reduction of CD11b expression and inhibition of CD11b-dependent monocyte adhesion to endothelium may crucially contribute to the clinical benefit of HMG-CoA reductase inhibitors in CHD, independent of cholesterol-lowering effects.

Long-term oral vitamin E supplementation in cystic fibrosis patients: RRR-alpha-tocopherol compared with all-rac-alpha-tocopheryl acetate preparations

To investigate the efficacy of three different vitamin E preparations for optimizing vitamin E status in cystic fibrosis (CF patients long-term, 29 patients (aged 0.7-29.8 y) were randomly assigned to receive 400 IU of either RRR-alpha-tocopherol (A: 268 mg, n = 10) or all rac-alpha-tocopheryl acetate as a fat-soluble (B: 400 mg, n = 10) or water-miscible preparation (C: 400 mg, n = 9) and were followed for 6 wk. In the whole study group, plasma alpha-tocopherol concentrations increased from baseline (10.5 +/- 4.6 micromol/L) to 3 wk (25.7 +/- 6.5 micromol/L; P < 0.001), but not further between 3 and 6 wk; concentrations at 3 and 6 wk did not differ from those of age-matched control subjects (23.6 +/- 3.9 micromol/L). There was no significant difference in the increase from baseline to 6 wk among preparations A (17.75 +/- 8.43 micromol/L), B (14.0 +/- 9.4 micromol/L), and C (15.5 +/- 7.1 micromol/L). Because of differences in body weight, the dose administered ranged from 5.5 to 47.4 IU x kg-1 x d-1; it correlated positively with the increase in plasma alpha-tocopherol concentrations (P < 0.001). There was no significant difference in the increase in plasma alpha-tocopherol concentrations between patients with CF-associated liver disease (n = 8) who received 10.2 +/- 3.8 IU x kg-1 x d-1 and those without liver disease taking comparable doses. We conclude that CF patients can be efficiently supplemented with 400 IU/d of any one of the three vitamin E preparations and plasma values of healthy control subjects can be achieved.

Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation

Plasma and platelet taurine concentrations were assayed in 39 patients with insulin-dependent diabetes mellitus (IDDM) and in 34 control subjects matched for age, sex, and both total and protein-derived daily energy intake. Platelet aggregation induced by arachidonic acid in vitro at baseline and after oral taurine supplementation (1.5 g/d) for 90 d was also studied. Plasma and platelet taurine concentrations (mean +/- SEM) were lower in diabetic patients (65.6 +/- 3.1 mumol/L, or 0.66 +/- 0.07 mol/g protein) than in control subjects (93.3 +/- 6.3 mumol/L, or 0.99 +/- 0.16 mol/g protein, P < 0.01). After oral supplementation, both plasma and platelet taurine concentrations increased significantly in the diabetic patients, reaching the mean values of healthy control subjects. The effective dose (mean +/- SEM) of arachidonic acid required for platelets to aggregate was significantly lower in diabetic patients than in control subjects (0.44 +/- 0.07 mmol compared with 0.77 +/- 0.02 mmol, P < 0.001, whereas after taurine supplementation it equaled the mean value for healthy control subjects (0.72 +/- 0.04 mmol). In in vitro experiments, taurine reduced platelet aggregation in diabetic patients in a dose-dependent manner, whereas 10 mmol taurine/L did not modify aggregation in healthy subjects.

Relationships between serum bilirubins and production and conjugation of bilirubin: Studies in Gilbert's syndrome, Crigler-Najjar disease, hemolytic disorders, and rat models

The pattern of serum bilirubins was determined in serum of humans and rats with unconjugated hyperbilirubinemia due to increased pigment load or defective hepatic conjugation. Bilirubin ester conjugates were present in all serum samples tested and were identified as bilirubin 1-O-acyl glucuronides. In Gilbert's syndrome, the concentration of total conjugates was comparable to the values in healthy control subjects. Because the concentration of unconjugated pigment was increased, the fraction of conjugated relative to total bilirubins was markedly decreased. Sera from patients with Crigler-Najjar disease differed from those with Gilbert's syndrome by the higher unconjugated bilirubin levels and the undetectability of diconjugated bilirubins. A striking finding was that in hemolytic disease, the concentration of both monoconjugates and diconjugates was enhanced in parallel with the increase of unconjugated pigment. Therefore, the fraction of conjugated relative to total bilirubins remained within the normal range. As in Gilbert's syndrome, heterozygote R/APfd-j/+ rats with impaired hepatic bilirubin conjugation exhibit an increased unconjugated bilirubin level in serum, whereas the concentration of total conjugates was comparable to the values in normal rats. In serum of normal rats loaded intraperitoneally with unconjugated bilirubin, both unconjugated and mono- and diconjugated bilirubins were increased in parallel so that the ratio of unconjugated to esterified pigment remained unaffected. Decreased hepatic conjugation or increased bilirubin load was associated with a lower percentage of diconjugates relative to total conjugates both in human and rat serum. The present results are consistent with a compartmental model in which there is bidirectional transfer across the sinusoidal membrane for unconjugated bilirubin as well as for the bilirubin glucuronides. Because typical patterns of serum bilirubins are found in Gilbert's syndrome and patients with hemolytic hyperbilirubinemia, determination of esterified bilirubins in serum is of value to study the pathophysiology and the differential diagnosis of unconjugated hyperbilirubinemia.