Peripheral inflammation exacerbates α-synuclein toxicity and neuropathology in Parkinson's models.

AIMS: Parkinson's disease and related disorders are devastating neurodegenerative pathologies. Since α-synuclein was identified as a main component of Lewy bodies and neurites, efforts have been made to clarify the pathogenic mechanisms of α-synuclein's detrimental effects. α-synuclein oligomers are the most harmful species and may recruit and activate glial cells. Inflammation is emerging as a bridge between genetic susceptibility and environmental factors co-fostering Parkinson's disease. However, direct evidence linking inflammation to the harmful activities of α-synuclein oligomers or to the Parkinson's disease behavioural phenotype is lacking. METHODS: To clarify whether neuroinflammation influences Parkinson's disease pathogenesis, we developed: (i) a 'double-hit' approach in C57BL/6 naive mice where peripherally administered lipopolysaccharides were followed by intracerebroventricular injection of an inactive oligomer dose; (ii) a transgenic 'double-hit' model where lipopolysaccharides were given to A53T α-synuclein transgenic Parkinson's disease mice. RESULTS: Lipopolysaccharides induced a long-lasting neuroinflammatory response which facilitated the detrimental cognitive activities of oligomers. LPS-activated microglia and astrocytes responded differently to the oligomers with microglia activating further and acquiring a pro-inflammatory M1 phenotype, while astrocytes atrophied. In the transgenic 'double-hit' A53T mouse model, lipopolysaccharides aggravated cognitive deficits and increased microgliosis. Again, astrocytes responded differently to the double challenge. These findings indicate that peripherally induced neuroinflammation potentiates the α-synuclein oligomer's actions and aggravates cognitive deficits in A53T mice. CONCLUSIONS: The fine management of both peripheral and central inflammation may offer a promising therapeutic approach to prevent or slow down some behavioural aspects in α-synucleinopathies.

Cost of reproduction. Changes in metabolism and endosulfan lethality caused by reproductive behavior in Hyalella curvispina (Crustacea: Amphipoda).

Biocides are periodically applied in agricultural activities, reaching aquatic systems and acting upon the biota. Amphipods are widely used in toxicity tests because of their sensitivity to a wide range of pollutants. In this work, we report the differential lethality of a widely used pesticide, endosulfan, on the amphipod Hyalella curvispina at two life stages and in three different adult groups, males and females separated by sex and both sexes grouped together. In addition, oxygen consumption of adult groups was determined as a way to estimate the role of behavioral activities and exposure to endosulfan in metabolism shifts. There were no differences between the LC(50) of juveniles and the adults when they were separated by sex (p>0.05). Nevertheless, the LC(50) of adults without sexual differentiation was significantly lower than the LC(50) of juveniles and adults separated by sex (p<0.05). The oxygen consumption rate was higher when adults were grouped without sexual differentiation in the control group. The exposure to low concentrations of endosulfan causes an increase in oxygen consumption in all the treatments. The sexual behavior increased the metabolism and the sensitivity to endosulfan. In future evaluations, adults grouped without sexual differentiation, which were the most sensitive group, should be included in order to mimic the environmental conditions. Using only juveniles or adults separated by sex in toxicity tests may inaccurately estimate the lethality of biocides, especially in species with constant reproductive activities.

Cost of a population-based programme of chest x-ray screening for lung cancer.

BACKGROUND: After the implementation of a population-based programme of chest x-ray (CXR) screening on smokers in Varese, Italy, lung cancer (LC) mortality was significantly reduced. Analysis of the incremental costs due to this type of screening programme is needed to evaluate its economic impact on the healthcare system. METHODS: In July 1997 a population-based cohort, consisting of all high-risk smokers (n=5,815) identified among 60,000 adult residents from the Varese province, was invited to a LC screening programme (an annual CXR for five years) in a general practice setting, and was observed through 2006. Invitees received National Health Service (NHS) usual care, with the addition of CXRs in screening participants. At the end of observation, among the 245 LCs diagnosed in the entire screening-invited cohort the observed LC deaths were 38 fewer than expected. To estimate the incremental direct cost due to screening in the invited cohort for the period July 1997-2006, we compared the direct cost of screening administration, CXR screens and LC management in the invited cohort and in the uninvited and unscreened controls in NHS usual care setting. RESULTS: Over the 9.5 years, the total incremental direct healthcare costs (including screening organization/administration, CXR screens, additional procedures prompted by false-positive tests, overdiagnosed LCs) were estimated to range from euro 607,440 to euro 618,370 (in euros as of 2012), equating to between euro 15,985- euro 16,273 per patient out of the 38 LC deaths averted. CONCLUSIONS: In a general practice setting, the incremental cost for a CXR screening programme targeted at all high-risk smokers in a population of 60,000 adults was estimated to be about euro 65,000 per annum, approx. euro 16,000 for each LC death averted.

Hypertension negatively affects the pregnancy outcome in patients with antiphospholipid syndrome.

The impact of hypertension in the pregnancies from autoimmune patients is not unequivocally defined. We have prospectively followed 168 pregnancies from 135 patients from four Italian centres to verify the potential impact of hypertension in the antiphospholipid syndrome (APS). The rate of preeclampsia, mean neonatal weight and gestational age at delivery were significantly lower in patients with both APS and hypertension than in patients with hypertension or APS alone. This information may be relevant for counselling and care of these patients.

Bullous lung disease and neurofibromatosis type-1.

Lung interstitial diseases and bullae are described as possible complications of neurofibromatosis type-1 (NF-1), a genetic disorder inherited as a autosomal-dominant trait. We report the case of a 16-year-old male non-smoker with NF-1, who presented with pneumothorax caused by ruptured lung bullae. The case of this young patient, successfully treated by video-assisted thoracoscopic resection of bullae, supports the concept that pulmonary alterations may be part of the NF-1 syndrome, rather than as an unrelated complication.

Fasting hyperglycaemia and in-hospital mortality in elderly population.

BACKGROUND: Admission hyperglycaemia has shown to be a marker of poor clinical outcome. The prevalence of admission hyperglycaemia and its relationship with in-hospital mortality in elderly population has not been clearly defined. We assessed the prevalence and prognostic significance of admission fasting hyperglycaemia in aged patients. METHODS: A total of 808 elderly patients were studied. Patients were classified into group I (serum glucose < 126 mg/dl), II (126-180 mg/dl) and III (> 180 mg/dl). Groups II and III were considered newly recognised fasting hyperglycaemia (NRFH) in non-diabetic patients. RESULTS: NRFH was present in 18.6%. After excluding diabetic patients (n = 206, 25.5%), the distribution of patients (n = 602, 74.5%) was as follows: group I (n = 452, 55.9%), group II (n = 122, 15.1%) and group III (n = 28, 3.5%). In the whole cohort, median fasting glucose was lower in patients who survived [105 mg/dl (88-135)] than in those who died [127 mg/dl (93-159), p < 0.001]. This significant difference was maintained only when non-diabetic patients were considered [100 mg/dl (87-122) vs. 118 mg/dl (92-149), p < 0.001]. In-hospital mortality rate in groups I, II and III was 8.5%, 14.1% and 22.9%, respectively (p < 0.001). Mortality rate was 8.4%, 18.0% and 32.1% (p < 0.001) in groups I, II and III, respectively in non-diabetic population. Both low albumin and high glucose serum concentrations were the only independent risk factors for in-hospital all-cause mortality in non-diabetic patients. CONCLUSIONS: In non-diabetic elderly patients admitted for acute disease, serum glucose concentration is an important, simple and independent predictor of hospital mortality.

Dopamine transporter regulation during four nights of REM sleep deprivation followed by recovery--an in vivo molecular imaging study in humans.

OBJECTIVES: To assess the influence of total or selective REM sleep deprivation on the dopamine transporter (DAT) densities and sleep patterns of healthy volunteers. DESIGN: Prospective study. SETTING: Evaluation of polysomnography recordings and DAT density after 4 nights of selective REM sleep deprivation followed by 3 nights of sleep recovery compared to a control group and a group that was subjected to 2 nights of total sleep deprivation. Single positron emission computed tomography and [99mTc]TRODAT-1 were used to assess the cerebral DAT density in the striatum at baseline, after REM sleep deprivation and total sleep deprivation as well as after sleep recovery. Blood was collected daily to examine prolactin and estradiol levels, which were correlated with dopaminergic activity. PATIENTS OR PARTICIPANTS: Thirty healthy male volunteers ranging from 19 to 29 years of age were randomly assigned to one of three experimental groups after giving written informed consent (10 non-sleep deprived, 10 total sleep deprived, and 10 REM sleep deprived). MEASUREMENTS AND RESULTS: Four nights of REM sleep deprivation and 2 nights of total sleep deprivation induced distinct and heterogeneous patterns of sleep recovery. No significant modulation of DAT availability was observed within groups. In the recovery nights, changes in cortisol, prolactin and estradiol concentrations were significantly correlated with specific sleep stages in the total and REM sleep deprived groups. In addition, DAT density was positively correlated with estradiol concentration and inversely associated with SWS latency only after total sleep deprivation. CONCLUSION: Our study demonstrates that although sleep deprivation did not promote significant alterations in DAT density within the striatum, there were significant correlations among transporter availability, hormonal concentrations and sleep parameters.

Microplastic in marine environment: reworking and optimisation of two analytical protocols for the extraction of microplastics from sediments and oysters.

Marine sediments and sessile biota (i.e. oysters) are nowadays recognised to be affected by microplastic (MP) pollution. NOAA proposes two distinct MP extraction protocols for sandy and bed sediments, which, however, were already demonstrated to suffer from many limitations. Conversely, to what concern oysters, works already published are usually time consuming, requiring a KOH 24-48 h oxidation step. The aim of this study is to show how iterative adaptation of the NOAA protocol allows to extract MPs, included PET, from marine sediments, regardless their characteristics. The method tested on PE-LD/PET/PA/PE-HD is based on density separation and oxidation treatments which were both carefully tuned, obtaining final recoveries higher than 85% for all the micropolymers (100% for PE and PA). Furthermore, a new protocol for the extraction of MPs from oysters was assessed, highlighting its efficacy (recoveries higher than 84% for all the plastics) and time-saving peculiarity. Finally, both protocols were successfully applied in the MPs extraction from real samples from Atlantic Ocean.•The extraction of PE-LD/PET/PA/PE-HD was optimised in sediments (regardless their characteristics) and oysters.•For sediments, density separation and oxidation procedures were carefully optimised.•For oysters, oxidation times were reduced from 24 to 48 h to 1 h.

Can plasma glucose and HbA1c predict fetal growth in mothers with different glucose tolerance levels?

To assess whether HbA1c and plasma glucose predicts abnormal fetal growth, 758 pregnant women attending 5 Diabetic Centers were screened for gestational diabetes mellitus (GDM). On glucose challenge (GCT) at 24-27 weeks of gestation (g.w.), negative cases formed the normal control group (N1). Positive cases took an oral glucose tolerance test (OGTT): those found negative were classed as false positives screening test (N2); if they had an OGTT result at least as high as their normal glucose levels, they were classed as having one abnormal glucose value (OAV) at OGTT; two values as GDM. HbA1c was assayed on the day of GCT. We considered fetal macrosomia, large for gestational age (LGA), ponderal index and mean growth percentile. Mean age, pre-pregnancy BMI, fasting plasma glucose (FPG) and HbA1c were progressively higher from N1 to GDM patients. The newborn of N2 mothers were heavier than those with N1 or GDM. The mean growth percentile was significantly higher in N2 than in N1. More LGA babies were born to OAV than to N1 or N2 women. Macrosomia and ponderal index did not differ significantly in the four groups. At logistic regression only plasma glucose at GCT could predict LGA babies and a ponderal index above 2.85. At risk analysis, GDM and OAV significantly predicted LGA babies, and GDM a ponderal index >2.85. In conclusion, FPG at GCT could predict fetal overgrowth and plasma glucose >85mg/dl doubles the risk of LGA infants. HbA1c at 24-27g.w. does not predict fetal overgrowth. Mild alterations in glucose tolerance correlate with fetal overgrowth and needs monitoring and treatment.

[Extramedullary hematopoyesis: compensatory mechanism or clinic syndrome? Case report and review of literature]. / Hematopoyesis extramedular: ¿mecanismo compensador o síndrome clínico? Descripción de un caso y revisión bibliográfica.

Extramedullary hematopoiesis (EMH) is a compensatory mechanism occurring in patients with chronic anemia. Liver, spleen, and lymph nodes are frequently involved. However, EMH may also develop in several sites such as thymus, kidneys, retroperitoneum, paravertebral areas of the thorax, lungs, bowel and others. Rarely symptomatic, it often shows a variety of clinical features. This condition, frequently, may be fatal. A correct early diagnosis of EHM might avoid, if possible, a bad prognosis. The Authors report a case where bone marrow cells were identified in centrifuge cerebrospinal fluid of a patient suffering from non-Hodgkin lymphoma.

Lymphscintigraphic evaluation of manual lymphatic drainage for lower extremity lymphedema.

To evaluate the effect of manual lymphatic drainage on technetium-99m-labeled dextran (99mTcDx) transport, 16 patients with lymphedema of lower extremities underwent two lymphscintigraphy exams by injecting 99mTcDx intradermally into the first interdigital space of the affected extremity. The first was a control examination at rest followed by an examination which included a manual lymphatic drainage session after the injection of the 99mTcDx. Images were obtained 45 minutes and three hours after the injection of the radioisotope. Extremity volumes were also measured before and after the drainage session. The findings from the examinations were assessed in a quantitative, semiquantitative and qualitative manner and compared without and with drainage. The analyses of the extremities' circumference before and after the drainage by paired t-test revealed a significant decrease. The analyses of the quantitative, semi-quantitative and qualitative evaluations evidenced no significant difference, without or with drainage, within the 45-minute and three-hour periods. Thus, manual lymphatic drainage caused an effective reduction in the circumference of the extremities but did not have a significant effect in the transport of 99mTcDx.

Haploidentical hematopoietic stem cell transplantation in children with high-risk hematologic malignancies: outcomes with two different strategies for GvHD prevention. Ex vivo T-cell depletion and post-transplant cyclophosphamide: 10 years of experience at a single center.

Forty patients with high-risk hematologic malignancies, median age 9 years, underwent haploidentical-HSCT from April 2005 to April 2015. Seventeen patients were transplanted with CD3-depleted PBSCs by negative selection (TCD group) following a reduced-intensity conditioning regimen (RIC), and 23 patients received T-cell-replete PBSCs followed by post-transplantation cyclophosphamide (PT-Cy group) after myeloablative conditioning (n=16) or RIC (n=7). Outcomes are reported for the TCD and PT-Cy recipients, respectively. Engraftment was achieved in 88% versus 100%. Median time to neutrophils>500/µL was 10 days versus 15 days. Platelets>20 000/µL occurred at a median of 16 days versus 20 days, respectively. Transplant-related mortality (TRM) was 24% versus 26% at 1 year. The cumulative incidence (CI) of grade III-IV acute GvHD was 7% versus 5%, and chronic GvHD 9% versus 53% (P=0.029). Relapse at 2 years was 31% versus 24%. Actuarial overall survival rates at 2 years were 47% versus 48%. Causes of death were infections (n=3), sinusoidal obstructive syndrome (n=4), acute GvHD (n=2) and relapse (n=9). These results indicate that haploidentical-HSCT is feasible in Uruguay. The TRM rate is of concern and should be the focus of continuing attention. Chronic GvHD risk was higher in the PT-Cy approach, so modifications are justified.

Insulin antibodies do not preclude optimization of metabolic control in women with IDDM during pregnancy.

OBJECTIVE: To evaluate whether the presence of insulin antibodies (IAs) may preclude the optimization of metabolic control during pregnancy and affect outcome in women with IDDM. RESEARCH DESIGN AND METHODS: IAs were measured by radiobinding assay in 44 women with IDDM referred to the Diabetes and Pregnancy Outpatients' Clinic during 46 pregnancies. Age, duration of IDDM, metabolic control (HbA1c, mean pre- and postprandial capillary blood glucose, frequency of hypo- or hyperglycemia), insulin requirement at 1st and 3rd trimester of pregnancy, BM1, and weight gain were recorded. Neonatal variables such as gestational age, weight, length, and the presence at birth of either hypoglycemia, hypocalcemia, or jaundice requiring phototherapy were also considered. RESULTS: IAs correlated positively with insulin requirement (P < 0.05) and negatively with HbA1c at term (P < 0.01). Patients with IA levels > or = 40% insulin binding (8 of 46) had a higher insulin requirement and lower preprandial capillary blood glucose at the beginning of pregnancy but not at term (P < 0.005), whereas they had lower HbA1c at term than did patients with low IA levels (P < 0.01). IA levels decreased slightly at term (P = 0.007). IA levels > or = 40% were not associated with a higher rate of hypo- or hyperglycemic episodes or with diabetic complications or thyreopathy. No correlation was found between 1A levels and any of the neonatal variables considered. CONCLUSIONS: The presence of IAs does not preclude optimization of metabolic control during pregnancy and is compatible with a favourable outcome.

Low prevalence of islet autoantibodies in patients with gestational diabetes mellitus.

OBJECTIVE: To determine the proportion of patients with gestational diabetes mellitus (GDM) who have serological characteristics typical of IDDM. RESEARCH DESIGN AND METHODS: Islet cell antibodies (ICAs), insulin autoantibodies (IAAs), GAD65, and IA-2 antibodies were measured in 145 pregnant women with GDM, 33 with impaired glucose tolerance (IGT), and in 73 with normal glucose tolerance (NGT). ICAs were measured by indirect immunofluorescence; GAD65 and IA-2 antibodies, by a radio-ligand immunoassay incorporating 35S-labeled recombinant antigen; and IAAs, by a liquid-phase radiobinding assay. RESULTS: The prevalences of islet autoantibodies were low and not significantly different between groups. ICAs were detected at levels ranging from 5 to 45 Juvenile Diabetes Foundation U in 14 (10%) women with GDM, 2 (6%) women with (GT, and in 4 (5%) women with NGT. IAAs were detected at levels between 3 and 4 SD above the mean in 4 (3%) women with GDM, 0 women with IGT, and in 1 (1%) woman with NGT. None had both ICAs and IAAs. Neither GAD65 nor IA-2 antibodies, which have been detected in the majority of pre-IDDM and IDDM patients, were found in NGT, IGT, or GDM patients. CONCLUSIONS: Low-titer ICAs and IAAs are not infrequent in pregnant women, but multiple islet autoantibodies and antibodies to GAD65 or IA-2 were not found in GDM. These findings suggest that the serological characteristics of IDDM are rare in GDM.

Screening for gestational diabetes in the Lombardy region: A population-based study.

AIM: As the treatment of hyperglycaemia during pregnancy with diet or insulin reduces the risk of adverse maternal outcomes and perinatal complications, screening for gestational diabetes mellitus (GDM) is included, albeit to variable extents, in all guidelines of care for pregnant women. The aim of the present investigation was to estimate the proportion of pregnancies screened for GDM in Lombardy between 2007 and 2010, and to identify predictors of screening. METHODS: A retrospective cross-sectional study using regional healthcare utilization databases of Lombardy was conducted. The study included all residents of Lombardy without pregestational diabetes who delivered between 1 January 2007 and 31 December 2010. The proportion of pregnancies with at least one screening test for GDM was calculated, along with the odds ratios and 95% confidence intervals associated with selected covariates for GDM screening. RESULTS: Of the 362,818 pregnancies included in the sample, 30% were screened for GDM. The proportion of pregnancies screened increased slightly from 2007 (27%) to 2010 (33%) and with maternal age (from 28% among women<25 years to 32% among those ≥35 years), and varied widely across local health management organizations (HMOs) of residence (range: 20% to 68%). Socioeconomic indicators (education, immigrant status), obstetric history and prepregnancy hypertension were independent predictors of GDM screening. CONCLUSION: The study finding of a low rate of pregnant women screened for GDM among residents of Lombardy supports the need for programmes to improve training of healthcare professionals, to raise women's awareness of GDM and to eliminate barriers to GDM screening.

Comparação das artérias carótidas comuns de equinos e muares por ultrassonografia modo-B e Doppler espectral e a relação com a massa corpórea / Comparison of the common carotid arteries of horses and mules by B-mode and Doppler spectral ultrasonography and the relation with body mass

A ultrassonografia convencional e o Doppler espectral nas artérias carótidas comuns em equinos e muares são considerados escassos, diferentemente do que ocorre na medicina humana. Este trabalho propôs comparar as artérias carótidas comuns de equinos e muares por ultrassonografia modo-B e Doppler espectral, além de verificar as diferenças dessas variáveis entre os gêneros desses animais e a relação com a massa corpórea. Foram avaliados os seguintes parâmetros: massa corpórea, diâmetros das artérias, espessura da camada íntima-média (EIM), índice de resistividade (IR), índice de pulsatilidade (IP), velocidade sistólica (VS), velocidade diastólica (VD) e velocidade média (VM). Salvo a massa corpórea, esses parâmetros foram obtidos de três regiões (cranial, médio e caudal) e submetidos à análise conjuntamente. Os diâmetros das artérias carótidas comuns são diferentes entre equinos e muares, com valores menores nos equinos. O IR, o IP, a VS e a VM diferiram entre equinos e muares, sendo maiores nos equinos, e a VD superior nos muares. Não foi observada diferença das variáveis do modo-B e Doppler entre gêneros nos equinos, diferentemente dos muares, cujos machos apresentaram valores maiores do diâmetro, do IR e do IP, mas menores da VS e da VM. A massa corpórea não influenciou as variáveis do modo-B, independentemente do gênero, mas apresenta correlação significativa nas variáveis do modo Doppler. As artérias carótidas comuns de equinos e muares são diferentes pelos exames ultrassonográficos modo-B e Doppler espectral. O gênero não influencia no modo-B e no Doppler nos equinos, porém influencia parcialmente nos muares. A massa corpórea de equinos e de muares, independentemente do gênero, não tem associação com as variáveis do modo-B, apenas com o Doppler.(AU)

Conventional ultrasound and spectral Doppler in the common carotid arteries in horses and mules are considered scarce, different from human medicine. The aim of this study was to compare the common carotid arteries of horses and mules by B-mode ultrasonography and spectral Doppler ultrasonography, as well as to verify the differences of these variables between their genders and the relation with body mass. The following parameters were evaluated: body mass, artery diameter, intima-media thickness (EIM), resistivity index (IR), pulsatility index (IP), systolic velocity (VS), diastolic velocity (VD) and average velocity (VM). Besides the body mass, the other variables were obtained from three regions (cranial, medium and caudal) and analyzed together. The diameters of the common carotid arteries are different between horses and mules, being smaller in horses. The IR, IP, VS and VM differed between horses and mules, being higher in the horses, but the VD was higher in mules. No difference in the variables in B-mode and Doppler between gender were observed in horses, different from mules, in which the diameters, IR and IP values were higher in males and the VS and VM was higher in females. Body mass did not influence B-Mode, both for horses and mules. A significant correlation was observed for Doppler. The common carotid arteries of horses and mules are different by ultrasound scans B-mode and spectral Doppler. Gender does not influence the B-Mode and Doppler variables in horses, but can in mules. The body mass of horses and mules, regardless of gender, is not associated with B-mode variables, but with Doppler variables.(AU)

Predictive value of plasma thrombomodulin in preeclampsia and gestational hypertension.

In a prospective longitudinal study, 130 primigravidae at risk for preeclampsia were examined and plasma sampling performed in 45 of them. Plasma thrombomodulin (pTM) was sequentially measured at weeks 12, 24 and 32 of gestation and after delivery in 20 primigravidae who developed either mild preeclampsia (n = 8) or gestational hypertension (n = 12) between weeks 32 and 39 of gestation and in 25 (age-matched) primigravidae who had uneventful pregnancies. pTM elevations were not observed until week 32 in uneventful pregnancies, but were present by week 24 (p = 0.002) in patients who later developed hypertensive complications. A net individual pTM increase > or = 4.2 ng/ml between weeks 12 and 24 (more than 8 times that of normotensive primigravidae) and/or pTM level > or = 47.5 ng/ml at week 32 predicted the development of hypertensive complications with 80% accuracy. Serial pTM determinations can be useful to select pregnancies who may benefit from early pharmacological intervention.

Visceral leishmaniasis in a patient treated for polyarteritis nodosa.

We report a case of visceral leishmaniasis in a patient receiving steroids and cyclophosphamide for polyarteritis nodosa. The clinical presentation of leishmaniasis, with fever, pancitopenia and hypergammaglobulinemia may be confused with a reactivation of vasculitis or with other non-infectious conditions such as haematologic diseases. In endemic areas, the case of latent leishmaniasis must be considered and serology for Leishmania should be performed before starting immunosuppressive treatment.

Interindividual variability of the human hepatic sulphotransferases.

The variability among subjects of the hepatic activities of O-sulphotransferase towards dopamine, p-nitrophenol, testosterone and ethinyloestradiol and of N-sulphotransferase with 1,2,3,4-tetrahydroisoquinoline (TIQ) as substrate is described. The rates of testosterone and TIQ sulphation were higher in men than women whereas those of ethinyloestradiol, dopamine and p-nitrophenol were similar in both sexes. The sulphotransferase activities towards p-nitrophenol and dopamine were positively skewed whereas those towards ethinyloestradiol approached normality. The coefficients of variations for the sulphotransferase activities ranged between 34% and 62% indicating a considerable variability among subjects. The rates of dopamine-, TIQ- and p-nitrophenol-sulphation were measured in the mucosa of the human intestine, and the duodenum/liver ratios were 10, 0.9 and 0.1, respectively. Thus the contribution of the intestine in the sulphation of xenobiotics is substrate dependent.

Glutathione conjugation with 1-chloro-2,4-dinitrobenzene (CDNB): interindividual variability in human liver, lung, kidney and intestine.

The rate of glutathione conjugation with 1-chloro-2,4-dinitrobenzene (CDNB) was measured in specimens of human liver (n = 93), sigmoid colon (n = 56), renal cortex (n = 67) and lung (n = 68). In the liver there was a weak but significant (r = - 0.247 p = 0.017) negative correlation between the activity of glutathione transferase and the liver donor's age. Such a correlation was not found in the renal cortex, lung and colon. In the renal cortex and in lung the rate of glutathione conjugation with CDNB was a little but significantly (p < 0.05) higher in women than men, whereas no sex-dependent difference was observed in the liver and colon. The distribution of glutathione transferase activity was polymorphic in the mucosa of colon and renal cortex of men but not in that of women. Smoking seems not to affect the glutathione conjugation rate with CDNB in lung. The activity of glutathione transferase was 2-, 6-, and 7-fold greater in liver than in the renal cortex, lung and colon, respectively. There was a large interindividual variability of the hepatic glutathione transferase activity, and because this variability, 15% of the population studied catalyzed the glutathione conjugation with CDNB at a rate similar to those of the renal cortex and duodenum. The subjects with low expression of the hepatic glutathione transferase should be more exposed to the effects of toxic and carcinogenic compounds.