Cardiovascular risk in women with polycystic ovarian syndrome (PCOS)

AIMS: Studies have suggested that polycystic ovary syndrome (PCOS) is associated with increased cardiovascular risk. The aim of this study was to examine cardiovascular risk profiles in women with PCOS compared with healthy age and weight matched control subjects using novel biochemical and biophysical markers. METHODS: After ethics committee approval, 11 women with PCOS and 12 controls were recruited (mean age, 32; SD, 6.5 years; mean body mass index (BMI), 33.1; SD, 5.9 kg/m2). Serum was analysed for lipid and lipoprotein profile (total and high density lipoprotein cholesterol, triglycerides, apolipoprotein B-100, apolipoprotein A1, lipoprotein (a)), and sialic acid, fibrinogen, homocysteine, and C reactive protein (CRP) concentrations. Endothelial function was also assessed by a standard venous occlusion plethysmography technique to measure reactive hyperaemic forearm blood flow (RH), and expressed as per cent increase from baseline. RESULTS: There were no significant differences in glucose, lipid, or lipoprotein concentrations between the two groups. Furthermore, sialic acid (PCOS: mean, 70.5; SD, 149 mg/litre; controls: mean, 71.3; SD, 112 mg/litre), fibrinogen (PCOS: mean, 3.1; SD, 1.0 g/litre; controls: mean, 3.3; SD, 0.7 g/litre), CRP (PCOS: mean, 4.6; SD, 4.2 mg/litre; controls: mean, 5.41 SD, 5.5 mg/litre), and RH (PCOS: mean, 158.7; SD, 135.5%; controls: mean, 200.1; SD, 114.2%) were similar. CONCLUSIONS: There were no differences in surrogate markers of the processes linked to enhanced cardiovascular risk between patients with PCOS and weight matched controls.     

Dimethylarginines in chronic renal failure

BACKGROUND: Nitric oxide (NO) is a potent chemical mediator involved in many functions. In vivo production of NO is thought to be regulated by endogenous analogues of L-arginine: asymmetric dimethylarginine (ADMA). AIM: To examine the effect of renal function and dialysis on the serum concentrations of ADMA and symmetric dimethylarginine (SDMA). METHODS: Blood samples were obtained from nine healthy subjects, patients with renal failure before (n = 17) and after haemodialysis (n = 9), nine patients on chronic ambulatory peritoneal dialysis (CAPD), and 13 patients with chronic renal failure on conservative treatment. Serum samples were extracted using a solid phase cation exchange column and the extracts were analysed by high performance liquid chromatography (HPLC). RESULTS: Serum concentrations of ADMA in patients with renal failure (mean, 1.04 micromol/litre; SD, 0.17) were significantly higher than those of controls (mean, 0.61 micromol/litre; SD, 0.13). Haemodialysis significantly decreased the serum concentration by 36% (before dialysis: mean 0.99 (SD, 0.25) micromol/litre; after dialysis: mean, 0.63 (SD, 0.15) micromol/litre). Serum SDMA concentrations were higher in patients with renal failure, and haemodialysis decreased the concentration by 60%. There was no difference in serum arginine concentrations between the groups. CONCLUSION: Serum concentrations of ADMA are increased in renal failure and haemodialysis reduces the concentration.     

Glutathione in gingival crevicular fluid and its relation to local antioxidant capacity in periodontal health and disease.

AIMS: To determine possible changes in gingival crevicular fluid (GCF) antioxidant defence in chronic adult periodontal disease and to investigate the nature of the local radical scavenging mechanisms, with particular reference to glutathione. METHODS: GCF and plasma were collected from patients with chronic periodontitis and age and sex matched control subjects (n = 10). Polymorphonuclear leucocytes (PMNLs) were prepared and gingival epithelial cells (GECs) were collected by conventional methods from periodontally healthy subjects. PMNL were stimulated with F-Met-Leu-Phe after cytochalasin B treatment. Enhanced chemiluminescence was used to determine the total antioxidant capacity and to investigate the activity of cell fractions and reducing agents. GCF concentrations of reduced (GSH) and oxidised (GSSG) glutathione were determined by high performance liquid chromatography. RESULTS: Plasma and GCF from patients contained lower mean (SD) total antioxidant capacity (501.8 (123) micro M Teq/litre and 658.3 (392) micro M Teq/litre, respectively) compared with controls (577.9 (99.8) and 1351.5 (861) micro M Teq/litre, respectively). Antioxidant light recovery profiles for GCF demonstrated a stepped response, not seen in plasma, which was inhibited by N-ethylmaleimide. This response was also detected in the cytosolic fraction of GEC and anaerobically stimulated PMNL. Similar antioxidant profiles, inhibitable by N-ethylmaleimide, were obtained with cysteamine, cysteine, and GSH. Control GCF contained high mean (SD) concentrations of glutathione (GSH, 1899.8 (494.4) micro M; GSSG, 256.8 (152.4) micro M). GCF from patients with periodontitis contained significantly lower amounts of GSH (mean, 1183.1; SD, 580.3 micro M) and GSSG (mean, 150.1; SD, 44.9 micro M). CONCLUSIONS: GSH values and total antioxidant capacity are reduced in chronic periodontal disease. The high concentrations of GSH present in GCF in health are similar to those found extracellularly in the lung and may represent an important antioxidant and anti-inflammatory defence strategy common to exposed epithelial surfaces.     

Alcohol estimation at necropsy: epidemiology, economics, and the elderly.

AIMS: To gather data on blood alcohol concentrations in a forensic necropsy population and to analyse the information on trends that may predict where alcohol testing is going to prove cost-effective. METHODS: Alcohol assays were performed on blood, urine, and vitreous samples in 1620 consecutive medicolegal necropsy examinations. RESULTS: Alcohol was detected in only 7% of natural deaths from all causes and in four of 40 deaths categorised as unknown/obscure. Alcohol concentrations > or = 350 mg/100 ml were found in nine drug/alcohol abuse deaths (range 362-506 mg/100 ml), five accidental deaths (356-504 mg/100 ml), and one homicide victim (400 mg/100 ml). Those categorised as alcohol abusers were represented in all but one category of death (unknown/obscure deaths in males), showing that many true alcoholics die with their alcoholism rather than of it; 39% of males and 34% of females with histories of alcohol abuse had alcohol present in their blood at necropsy at concentrations > or = 50 mg/100 ml, v only 9% (male) and 6% (female) without such history. CONCLUSIONS: The study highlights the problems of elderly and "hidden" alcoholics and illustrates cases where routine assays would provide additional significant information. Routine alcohol testing is useful in all cases of suspected unnatural death but universal testing of forensic necropsies is not cost-effective.     

Concentrations of temafloxacin in serum and bronchial mucosa

The bronchial mucosal concentrations of temafloxacin hydrochloride were determined in specimens obtained at fibreoptic bronchoscopy and compared with simultaneous serum concentrations. The 18 patients studied were given an oral dose of 400 mg b.i.d. for three days to achieve steady state levels. The mean serum concentration was 6.9 mg/l (SD 2.5 mg/l) and the mean bronchial mucosal concentration 12.2 mg/kg (SD 4 mg/kg). The mucosal levels exceeded those required to inhibit most of the common respiratory pathogens, includingStreptococcus pneumoniae andPseudomonas aeruginosa. These data support the use of temafloxacin for therapy of bronchial infections.     

Reduction of erythrocyte magnesium concentration in heterozygote beta-thalassaemic subjects and in normal subjects submitted to physical stress

Erythrocyte and serum magnesium (Mg) concentrations have been assayed in a group of sedentary heterozygote beta-thalassaemic subjects (beta-thal), in a group of non-thalassaemic well trained runners before and after a 25 km running race, and in a group of sedentary healthy controls. The mean erythrocyte Mg concentration (EMg) found in beta-thal (2.72 mEq/litre) and in runners, both before and after the race (2.58 mEq/litre before, 3.10 after), was significantly lower than the EMg values from the control group (3.69 mEq/litre). We propose various hypotheses to explain the reductions observed.     

Pre-beta-migrating lipoprotein A-I concentration in normal full-term maternal blood]

Hyperlipidemia in pregnancy accompanying selectively-raised concentrations of serum apolipoprotein A-I (apoA-I) and high-density lipoprotein-2-cholesterol (HDL2-C) had been considered to be, at least in part, mediated by sex hormones. On the other hand, it is known that oral estrogen-replacement therapies in postmenopausal women raise serum concentrations of lipoprotein A-I without apoA-II (LpA-I) originated from the liver. This study was performed to clarify the relations among the concentrations of pre-beta-migrating LpA-I (pre-betaLpA-I) and of serum apoA-I and of HDL-C. And we discussed the origin of pre-beta LpA-I in normal full-term maternal blood. Pre-beta LpA-I concentrations in 12 maternal (mean +/- SD = 33.8 +/- 7.6 mg/dl) and umbilical cord blood (mean +/- SD = 3.1 +/- 1.9 mg/dl) pairs and those in 20 healthy non-pregnant adult female controls (mean +/- SD = 13.5 +/- 6.1 mg/dl) were determined using the crossed immunoelectrophoresis. (1) The higher concentration of maternal pre-beta LpA-I than that of control was contributed to the high concentration of maternal serum apoA-I but not to the high concentration of maternal HDL-C, so it would loosen the correlativity between serum apoA-I concentration and HDL-C concentration because pre-beta LpA-I was cholesterol-poor. (2) It did not correlate with the high concentration of chylomicron, which made us speculate that maternal pre-betaLpA-I might be possible to be originated from the liver by the action of endogenous estrogen. And, (3) no correlation between the concentrations of pre-beta LpA-I from maternal blood and those from cord blood respectively will support the idea that their lipoprotein metabolisms would be independent with each other.     

Salicylic acid in the serum of subjects not taking aspirin. Comparison of salicylic acid concentrations in the serum of vegetarians, non-vegetarians, and patients taking low dose aspirin

AIMS: To determine serum salicylic acid concentrations in non-vegetarians and vegetarians not taking salicylate drugs, and to compare these concentrations with those found in patients taking aspirin, 75 mg daily. METHODS: Serum samples were obtained from vegetarians (n = 37) and non-vegetarians (n = 39) not taking salicylate drugs. Non-vegetarians and vegetarians were recruited from the community and from a Buddhist monastery, respectively, in Dumfries and Galloway, Scotland. Patients (n = 14) taking aspirin (75 mg daily) were recruited from the Dumfries diabetic clinic. Serum salicylic acid concentrations were determined using a high performance liquid chromatography method with electrochemical detection. RESULTS: Salicylic acid was detected in every serum sample analysed. Higher serum concentrations of salicylic acid were found in vegetarians than non-vegetarians: median concentrations of 0.11 (range, 0.04-2.47) micromol/litre and 0.07 (range, 0.02-0.20) micromol/litre, respectively; the median of the difference was 0.05 micromol/litre (95% confidence interval for difference, 0.03 to 0.08; p < 0.0001). The median serum concentration of salicylic acid in patients taking aspirin (75 mg daily) was 10.03 (range, 0.23-25.40) micromol/litre, which was significantly higher than that found in non-vegetarians and vegetarians. There was overlap in serum salicylic acid concentrations between the vegetarians and patients taking aspirin. CONCLUSIONS: Salicylic acid, a non-steroidal anti-inflammatory drug, is present in fruits and vegetables and is found in higher concentrations in vegetarians than non-vegetarians. This suggests that a diet rich in fruits and vegetables contributes to the presence of salicylic acid in vivo. There is overlap between the serum concentrations of salicylic acid in vegetarians and patients taking aspirin, 75 mg daily. These findings may explain, in part, the health promoting effects of dietary fruits and vegetables.     

Triglycerides, cholesterol, and phospholipids in normal heart papillary muscle and in patients suffering from diabetes, cholelithiasis, hypertension, and coronary atheroma

The triglyceride, cholesterol, and phospholipid contents of heart papillary muscle were measured in groups of obviously healthy and diseased females and males on whom either routine or forensic necropsies were performed. In healthy men the triglyceride content was 1.77 +/- 1.30 mg/g of wet weight and in women 1.25 +/- 0.48 mg/g wet weight. The corresponding values for cholesterol were 1.07 +/- 0.24 mg/g and 1.21 +/- 0.22 mg/g and those for phospholipids 17.70 +/- 5.15 mg/g and 19.65 +/- 10.21 mg/g. The differences between the sexes were not significant.The hypertensive or cardiac hypertrophy group had about the same or slightly lower means for lipid content.In the cholelithiasis group, women had significantly high triglyceride values (3.38 +/- 2.36 mg/g). The cholesterol values were not significantly elevated in either men or women.In the diabetic group, triglycerides were significantly increased both in men (mean 8.12 +/- 0.54 mg/g) and in women (6.85 +/- 5.66 mg/g). The cholesterol mean values were also high in both sexes, but the rise was not significant because of the great variation.In the coronary atheroma group, both male and female hospital cases had high triglyceride contents (mean 4.48 +/- 4.25 mg/g and 3.65 +/- 3.94 mg/g) whereas the forensic cases had only slightly elevated or normal values. Cholesterol assays paralleled the triglyceride ones, but phospholipids showed an inverse trend.The results showed that the lipid content of papillary muscle was increased in diseases where disturbances of lipid metabolism are evident, as in diabetes and cholelithiasis. In coronary atheroma only those cases with advanced obstruction of the arteries were associated with abnormal values of papillary lipids. No increase of the lipid content with age alone was found, nor was there any correlation with obesity.     

Evaluation of serum theophylline concentrations following administration of sustained-release beads in applesauce to asthmatic preschool children

A sustained-release theophylline preparation (Theo-Dur Sprinkle) was evaluated in young asthmatic patients aged 1 to 6 years and receiving a daily dose of 23.4 +/- 2.0 mg/kg (mean +/- SD) to determine, on the basis of serial serum concentrations obtained over a 12-hour dosing interval at steady state, the suitability of such a product in patients likely to metabolize the drug very rapidly. Peak theophylline concentrations of 15.1 +/- 4.1 mg/L were achieved 5.5 +/- 1.5 hours after dosing. The mean maximum to minimum concentration difference was 6.9 +/- 2.2 mg/L for the dosing interval studied. Fluctuations in theophylline concentration less than 100% were achieved in nine of the 12 study patients. Use of the "sprinkle-technique" with Theo-Dur Sprinkle appears to be a simple and effective method of maintaining acceptable fluctuations in serum theophylline concentrations in preschool asthmatic children.     

Transcortinkonzentrationen im Plasma von Normalpersonen und Patienten mit Nieren- oder Lebererkrankungen

Summary The purpose of the study was to assess the influence of chronic kidney and liver diseases on the transcortin concentrations in plasma. The mean (±SD) plasma concentration of transcortin was 45.0±6.7 mg/l in women not taking oral contraceptive steroids and 41.2±6.7 mg/l in healthy male volunteers. Patients with the nephrotic syndrome had low transcortin concentrations (females: 20.9±8.5 mg/l; males: 26.0±6.0 mg/l). Abnormally low concentrations were measured in females treated for endstage renal disease with chronic ambulant peritoneal dialysis (CAPD) (30.8±7.5 mg/l). Patients on hemodialysis or with a functioning renal allograft had normal transcortin concentrations in plasma. Females suffering from a primary biliary cirrhosis had normal transcortin concentrations and male patients with an alcoholic cirrhosis had abnormally low mean transcortin concentrations in plasma (32.6±7.4 mg/l). The transcortin concentrations in patients with a Gilbert syndrome were normal. Among patients with a kidney or liver disease, the large variability of the transcortin concentration in plasma indicates that the knowledge of the transcortin concentration or the unbound steroid concentration in plasma is mandatory for the interpretation of total glucocorticoid concentrations in plasma.

Die Arbeit wurde unterstützt durch the Swiss National Foundation for Scientific Research (Grant No 3.914-0.82)     

Method for the measurement of antioxidant activity in human fluids

AIM: To develop a new, simple, and cheap method for estimating antioxidant activity in human fluids. METHODS: The assay measured the capacity of the biological fluids to inhibit the production of thiobarbituric acid reactive substances (TBARS) from sodium benzoate under the influence of the free oxygen radicals derived from Fenton's reaction. A solution of 1 mmol/litre uric acid was used as standard. RESULTS: The following mean (SD) antioxidative activities were found (as uric acid) in the various biological fluids: serum, 2.04 (0.20) mmol/litre; urine, 176.5 (25.6) micromol/litre; cerebrospinal fluid, 95.0 (26.9) micromol/litre; aqueous humour oculi, 61.25 (9.9) micromol/litre; saliva, 838.5 (48.2) micromol/litre; tears, 247.0 (17.0) micromol/litre; ascites fluid, 270.0 (63.3) micromol/litre; kidney cyst fluid, 387.1 (28.1) micromol/litre. Small samples of the biological material were needed for the analyses: 10 microl of serum and 50-100 microl of other body fluids. In the sera of 48 healthy individuals there was a significant positive correlation between values obtained with the Randox method (as a reference method) and the new method proposed here (correlation coefficient, 0.8728; mean difference between methods, <0.4%). CONCLUSIONS: This method is easy, rapid, reliable, and practical for the routine measurement of total antioxidant activity in serum and other human body fluids. Small samples of biological material are needed for the analyses and the results are comparable with the reference (Randox) method.     

Glutathione in gingival crevicular fluid and its relation to local antioxidant capacity in periodontal health and disease

Aims: To determine possible changes in gingival crevicular fluid (GCF) antioxidant defence in chronic adult periodontal disease and to investigate the nature of the local radical scavenging mechanisms, with particular reference to glutathione.

Methods: GCF and plasma were collected from patients with chronic periodontitis and age and sex matched control subjects (n = 10). Polymorphonuclear leucocytes (PMNLs) were prepared and gingival epithelial cells (GECs) were collected by conventional methods from periodontally healthy subjects. PMNL were stimulated with F-Met-Leu-Phe after cytochalasin B treatment. Enhanced chemiluminescence was used to determine the total antioxidant capacity and to investigate the activity of cell fractions and reducing agents. GCF concentrations of reduced (GSH) and oxidised (GSSG) glutathione were determined by high performance liquid chromatography.

Results: Plasma and GCF from patients contained lower mean (SD) total antioxidant capacity (501.8 (123) μM Teq/litre and 658.3 (392) μM Teq/litre, respectively) compared with controls (577.9 (99.8) and 1351.5 (861) μM Teq/litre, respectively). Antioxidant light recovery profiles for GCF demonstrated a stepped response, not seen in plasma, which was inhibited by N-ethylmaleimide. This response was also detected in the cytosolic fraction of GEC and anaerobically stimulated PMNL. Similar antioxidant profiles, inhibitable by N-ethylmaleimide, were obtained with cysteamine, cysteine, and GSH. Control GCF contained high mean (SD) concentrations of glutathione (GSH, 1899.8 (494.4)μM; GSSG, 256.8 (152.4)μM). GCF from patients with periodontitis contained significantly lower amounts of GSH (mean, 1183.1; SD, 580.3μM) and GSSG (mean, 150.1; SD, 44.9μM).

Conclusions: GSH values and total antioxidant capacity are reduced in chronic periodontal disease. The high concentrations of GSH present in GCF in health are similar to those found extracellularly in the lung and may represent an important antioxidant and anti-inflammatory defence strategy common to exposed epithelial surfaces.

     

In situ postmortem ethanol quantification in the cerebrospinal fluid by non‐water‐suppressed proton MRS

Determination of the ethanol concentration in corpses with MRS would allow a reproducible forensic assessment by which evidence is collected in a noninvasive manner. However, although MRS has been successfully used to detect ethanol in vivo, it has not been applied to postmortem ethanol quantification in situ. The present study examined the feasibility of the noninvasive measurement of the ethanol concentration in human corpses with MRS. A total of 15 corpses with suspected alcohol consumption before demise underwent examination in a 3 T whole body scanner. To address the partial overlap of the ethanol and lactate signal in the postmortem spectrum, non‐water‐suppressed single voxel spectra were recorded in the cerebrospinal fluid (CSF) of the left lateral ventricle via the metabolite cycling technique. The ethanol signals were quantified using the internal water as reference standard, as well as based on a reference signal acquired in a phantom. The measured values were compared with biochemically determined concentrations in the blood (BAC) and CSF (CSFAC). In 8 of the 15 corpses a BAC above zero was determined (range 0.03–1.68 g/kg). In all of these 8 corpses, ethanol was measured in CSF with the proposed MRS protocol. The two applied MRS calibration strategies resulted in similar concentrations. However, the MRS measurements generally overestimated the ethanol concentration by 0.09 g/kg (4%) to 0.72 g/kg (45%) as compared with the CSFAC value. The presented MRS protocol allows the measurement of ethanol in the CSF in human corpses and provides an estimation of the ethanol concentration prior to autopsy. Observed deviations from biochemically determined concentrations are mainly explained by the approximate correction of the relaxation attenuation of the ethanol signal.     

Generation of novel trimeric fragments of human SP-A and SP-D after recombinant soluble expression in E. coli

Surfactant treatment for neonatal respiratory distress syndrome has dramatically improved survival of preterm infants. However, this has resulted in a markedly increased incidence of sequelae such as neonatal chronic inflammatory lung disease. The current surfactant preparations in clinical use lack the natural lung defence proteins surfactant proteins (SP)-A and D. These are known to have anti-inflammatory and anti-infective properties essential for maintaining healthy non-inflamed lungs.Supplementation of currently available animal derived surfactant therapeutics with these anti-inflammatory proteins in the first few days of life could prevent the development of inflammatory lung disease in premature babies. However, current systems for production of recombinant versions of SP-A and SP-D require a complex solubilisation and refolding protocol limiting expression at scale for drug development.Using a novel solubility tag, we describe the expression and purification of recombinant fragments of human (rfh) SP-A and SP-D using Escherichia coli without the need for refolding. We obtained a mean (± SD) of 23.3 (± 5.4) mg and 86 mg (± 3.5) per litre yield of rfhSP-A and rfhSP-D, respectively. rfhSP-D was trimeric and 68% bound to a ManNAc-affinity column, giving a final yield of 57.5 mg/litre of highly pure protein, substantially higher than the 3.3 mg/litre obtained through the standard refolding protocol. Further optimisation of this novel lab based method could potentially make rfhSP-A and rfhSP-D production more commercially feasible to enable development of novel therapeutics for the treatment of lung infection and inflammation.     

Long-term therapy with paricalcitol for secondary hyperparathyroidism in hemodialysis patients

PURPOSE: The efficacy of the vitamin D analog paricalcitol has mainly been shown in short-term studies. There are limited data regarding long-term treatment with this agent. This purpose of this study was to determine long-term effects of paricalcitol therapy on parathyroid hormone (PTH) suppression and serum levels of calcium, phosphorus and calcium-phosphorus product (Ca x P). PATIENTS AND METHODS: Patients who received paricalcitol for > or = 3 months had the following data collected: demographics, drug dosage, serum PTH, corrected serum calcium concentration, serum phosphorus concentrations and serum Ca x P values. RESULTS: Sixteen patients received paricalcitol for a mean of 18 months. The mean +/- SD dose of paricalcitol was 0.13 +/- 0.12 mcg/kg. The mean +/- SD pre-paricalcitol serum PTH concentration was 705 +/- 423 pg/mL. PTH concentration did not change significantly over the duration of treatment (mean +/- SD: 821 +/- 480 pg/mL). The number of patients who had at least one corrected serum calcium concentration > or = 11.5 mg/dL, one serum phosphorus concentration > or = 6.5 mg/dL, or one Ca x P level > or = 70 were 75%, 94% and 82%, respectively. Hypercalcemia and elevated Ca x P value resulted in a mean of 17% of doses being withheld during therapy. CONCLUSION: During the study, PTH was not adequately suppressed by paricalcitol. This was primarily attributed to withholding paricalcitol doses due to elevated serum calcium and Ca x P levels.     

Bromine and thyroid hormone activity.

AIMS--To examine the possible consequences of high plasma concentrations of bromine on thyroid hormone. METHODS--Bromine was measured by inductively coupled plasma mass spectrometry in the plasma of 799 patients consulting for thyroid disorders. Because the mean (SD) bromine concentration in the plasma of healthy subjects is 4 (1) mg/l, concentrations above 6 mg/l were regarded as outside the normal range. Bromine, free thyroxine (FT4), and thyroid stimulating hormone (TSH) values were compared. RESULTS--The percentage of patients with normal, low, and high FT4 and TSH plasma activities, measured separately, did not differ between patients with low and high bromine concentrations. The percentage of patients with high TSH but normal FT4 values was significantly higher in the group with bromine values of more than 6 mg/l than in the group with bromine concentrations below this (p < 0.02). CONCLUSION--An increase in plasma bromine could potentiate an increase in plasma TSH concentration, probably as a consequence of a minor inhibitory effect on thyroid activity.     

Serum levels of beta-2-microglobulin-free heavy chain of HLA class I antigen in healthy individuals: relationship to their class I allotype

An ELISA-based double determinant immunoassay has been established to measure the soluble beta2-microglobulin (beta2m)-free heavy chain (FHC) of the HLA-B, -C (and HLA-A3, -A28 and -A30) class I molecular complex in sera from 212 HLA-typed healthy unrelated individuals. FHC was calculated by means of a standard curve constructed using serial concentrations of beta2m-associated HLA-class I heavy chain (HLA-I)/FHC purified from cultured human lymphoid cell C1R-sB7-supernatant. The mean FHC concentration (+/-SD) was 0.25 mg/l (+/-0.2). Its median concentration did not statistically differ between males and females, though the male/female ratio was greater in the high secretor (FHC >0.45 mg/l; mean + 1SD) than in the low secretor group (FHC < 0.05 mg/l; mean - 1SD). FHC < 0.05 mg/l was statistically (Fisher's exact test) associated with HLA-B17 (p = 0.003); FHC > 0.45 mg/l was statistically associated with HLA-B35 (p = 0.003) and -Cw4 (p = 0.002). None of these allele-positive groups showed a mean FHC concentration 1.5 times higher than that of the corresponding allele-negative ones. This allotype-dependent HLA-B and C FHC enhancement was less marked than that previously reported for HLA-I in individuals carrying HLA-A9 (and its splits). These results indicate that FHC could be a more valuable marker when its levels are compared among individuals carrying different allotypes. Moreover the lack of correlation between FHC and HLA-I levels measured in 52 HLA-A3, -A28 or -A30 positive individuals suggests that the two molecules may be regulated by different metabolic pathways and their serum expression may have a different biological significance.     

Helicobacter pylori infection and fasting plasma glucose concentration

BACKGROUND: Helicobacter pylori infection raises basal and meal stimulated serum gastrin concentrations and lowers iron stores, which may in turn reduce fasting plasma glucose concentrations in the population. AIM:To determine whether H pylori infection leads to lower fasting plasma glucose concentrations in the population. METHODS: One hundred and seventy three women and 165 men, randomly selected from the electoral rolls of an Australian city, participated in a cardiovascular risk factor survey. Plasma glucose concentrations and H pylori IgG antibody titres were measured. Non-fasting subjects and pregnant women were excluded, as were known diabetics, whose plasma glucose concentrations would be affected by diet and/or medications. Fasting plasma glucose concentrations were logarithmically transformed and the relation with H pylori infection, adjusting for age and other confounding factors, was determined for men and women separately by analyses of variance. RESULTS: Helicobacter pylori infection was significantly associated with fasting plasma glucose concentration among women. Infected women had a lower mean fasting plasma glucose concentration (5.2 mmol/litre; range, 3.9-8.2) than did non-infected women (5.4 mmol/litre; range, 3.9-11.1). CONCLUSIONS: Helicobacter pylori infection may lead to lower fasting plasma glucose concentrations among women and should be considered when interpreting concentrations bordering on diabetes.     

Influence of ethanol on systemic and pulmonary hemodynamics in anesthetized dogs

Immediate circulatory reactions to acute intragastric ethanol administration were studied by a catheterization technique in spontaneously breathing dogs. Diluted ethanol was given in a dosage of 1 g/kg in test group I (n = 11), and 2 g/kg in group II (n = 10). The control group (n = 14) received only water. The highest blood ethanol concentration was 0.90 ± 0.07 mg/ml (mean ± SE) in group I, and 1.97 ± 0.10 mg/ml in group II. Heart rate and cardiac output increased (p < 0.001), but stroke volume, mean aortic blood pressure and right atrial blood pressure remained practically unchanged. Systemic vascular resistance decreased. Mean pulmonary arterial blood pressure increased markedly in both test groups (p < 0.001) while pulmonary arterial wedge pressure did not change. The pulmonary arterial resistance increased (p xyl 0.01). Changes in respiratory rate or volume and arterial pO₂ were negligible in group I, but respiratory minute volume decreased in group II. In conclusion, ethanol in concentrations 0.5 to 2.0 mg/ml increased resistance in the pulmonary arterial tree, indicating pulmonary arterial vasoconstriction, but reduced systemic vascular resistance, thus putting a concept of peripheral vasodilation in favour.