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Biomedical subjects

M Hammami

Publications and source records attributed to M Hammami.

At least 19 recordsLinked to original sources

Foodstuffs and human blood contamination by the mycotoxin ochratoxin A: correlation with chronic interstitial nephropathy in Tunisia.

Ochratoxin A (OTA) has been detected in high amounts in human blood samples collected in nephrology departments in Tunisia from nephropathy patients under dialysis, especially those categorised as having a chronic interstitial nephropathy of unknown aetiology. These represent 12-26.1% of all chronic renal failure patients. To clarify the situation, food and blood samples were collected from nephropathy patients and controls, (with no familial case of nephropathy). The OTA assay showed very different scales of OTA food and blood contamination from 0.1 to 16.6 micrograms/kg and 0.1-2.3 ng/ml, respectively, in controls and healthy individuals and 0.3-46 830 micrograms/kg for food and 0.7-1136 ng/ml for blood in nephropathy patients. The disease seems related to OTA blood levels and food contaminations, since the control group was significantly different from the nephropathy group (p < 0.005) for both food and blood ochratoxin A contamination. Combined with data published already, the results emphasize the likely endemic aspect of this OTA-related nephropathy occurring in Tunisia and possibly in other countries of northern Africa. This nephropathy is very similar to Balkan endemic nephropathy.

Chronic Disease

Ochratoxin A in human blood in relation to nephropathy in Tunisia.

The determination of ochratoxin A (OTA) in human blood in Tunisian populations is underway. The range of contamination is between 0.7 to 7.8 ng ml-1 for the general population and 12 to 55 ng ml-1 for people suffering from chronic renal failure. It appears that 21 to 64% of people suffering from nephropathy are OTA positive with a detection limit of 1ng ml-1. This situation prompted us to search for possible association of OTA contamination and nephropathy resembling Balkan endemic nephropathy. The classification of the ill population into chronic interstitial nephropathy (CIN), chronic glomerular nephropathy (CGN), chronic vascular nephropathy (CVN) and others, indicated that the largest is the CIN group which is significantly different from the other groups, and from the control (P < 0.005). Furthermore, it presented the highest OTA mean values (25 to 59 ng ml-1) compared with the control, CGN, CVN and other groups (6 to 18 ng ml-1) according to the designated region in Tunisia. The rural population seems to be more exposed to ochratoxins in Tunisia, as has been previously reported in the Balkans and Western Europe. Altogether, these results emphasise that in Tunisia an endemic ochratoxin-related nephropathy is probably occurring.

Adult

[Mother-child transmission of hepatitis B virus in the Tunisian Sahel].

In order to assess the importance of mother-child transmission of the hepatitis B virus (HBV) in the Tunisian Sahel, 81 HBsAg-positive mothers have been selected at delivery in a representative sample of 1940 who delivered in maternities of this region. Each HBsAg-positive mother was matched for age and parity particularly with two HBsAg-negative mothers. Children born to these 66 HBsAg+ and 120 HBsAg- mothers were traced at 28 months and tested by ELISA for HBV serologic markers (HBsAg, anti-HBs and anti-HBc). The distribution of these markers was significantly different according to the maternal status for HBsAg. The overall prevalence rate of HBV markers was higher in children born to HBsAg+ mothers as compared to children born to HBsAg- mothers (33.3% vs 13.3%, OR = 2.5, 95% CI:1.4-4.2). For HBsAg, the figures were 27.3% and 9.2% respectively (OR = 2.9, 95% CI: 1.5-5.9). Given the prevalence rate of HBsAg in mothers (4.2%), the role of mother-child transmission in the spread of HBV infection and the intensity and precocity of horizontal transmission, systemic vaccination against HBV at birth should be recommended in the Tunisian Sahel in the context of the EPI. However this decision should take into account, in terms of cost/efficacy ratio, the other public health problems concerning this area.

Adult

Phenotypic expression of familial hypercholesterolaemia in central and southern Tunisia.

We studied 14 families with familial hypercholesterolaemia (FH) from Central and Southern Tunisia. Twenty-six living homozygotes were identified in these areas of whom 24 homozygotes and 27 of their obligate heterozygote parents are the subject of this report. Ten of the 14 families are unrelated and in 9 of them there were consanguineous marriages. The mean age of homozygotes was 16 for females (range 2.5-40) and 12.5 for males (range 2-34). All the homozygotes had extensive xanthomatosis and showed variable clinical manifestations of coronary heart disease (CHD). Plasma total and LDL cholesterol levels averaged 18 and 16.9 mmol/l, respectively. Mean high density lipoprotein (HDL) cholesterol values were 0.48 mmol/l for males and 0.70 mmol/l for females. The mean age of the obligate heterozygotes was 44 (range 32-62 years) for mothers and 51 (range 35-80 years) for fathers. None of them had tendon xanthomas, not even the oldest, who was aged 80. Only 5 of the 27 obligate heterozygotes had developed CHD (aged 34-58). Plasma cholesterol levels varied more than twofold (4.1-10 mmol/l) and averaged 6.79 and 7.51 mmol/l for males and females, respectively. LDL cholesterol values were below the age- and sex-related 95th percentile from the Lipid Research Clinics Prevalence Study in 46% of male and 30% of female heterozygotes. The frequency of homozygotes was 1:125,000 and the minimum estimated frequency of heterozygotes was 1:165 in Central and Southern Tunisia. Only Afrikaners in South Africa and French Canadians have such high frequencies of FH.

Adolescent

Isolation and structure determination of natural analogues of the mycotoxin ochratoxin A produced by Aspergillus ochraceus.

Three new natural mycotoxins, analogues of ochratoxin A, in which the phenylalanine moiety is replaced by serine, hydroxyproline or lysine, were isolated from cultures of Aspergillus ochraceus by TLC followed by HPLC column chromatography. Their structures were determined after acidic hydrolysis by the characterisation of both their amino acid moieties and of ochratoxin alpha, the chlorinated dihydroisocoumarin moiety of ochratoxin A. These structures were confirmed by mass spectrum analysis.

Aspergillus ochraceus

[Infantile cystinosis. A new Tunisian case].

A case of cystinosis in a three and a half-year-old is reported. Suggestive manifestations included severe rickets, small stature, and complex renal tubule dysfunction meeting the criteria for secondary Fanconi syndrome. Diagnosis was established by the discovery of retinal lesions upon ophtalmologic evaluation and, above all, by the finding that intracellular leukocyte cystine levels were increased to 16 mumol of 1/2 cystine per gram protein. Cystinosis is severe because it inevitably leads to renal failure. Much hope is currently placed in the use of cysteamine to delay this and other complications. At present, early antenatal diagnosis during the first ten weeks of pregnancy is needed in high-risk families to allow elective termination of pregnancy within the legal time limit.

Child, Preschool

Effect of rat plasma high density lipoprotein with or without apolipoprotein E on the cholesterol uptake and on the induction of the corticosteroid biosynthetic pathway in newborn rat adrenocortical cell cultures.

High density lipoprotein (HDL) has been shown to induce the cellular accumulation of cholesterol esters and the biosynthetis of 21-hydroxysteroids (corticosteroids) newborn rat adrenocortical cells cultivated in serum-free medium. In order to identify the component(s) of HDL responsible for these effects, we investigated the ability of rat HDL subfractions and HDL with or without apolipoprotein E to deliver cholesterol to cells and to stimulate the steroid biosynthetic pathways in adrenal cultured cells. The total cholesterol uptake from HDL2 was greater than that observed with HDL rich in apolipoprotein E (HDL1 and HDLc). Furthermore, the increase of the ratio between 21-hydroxysteroids and reductive metabolites of progesterone was higher with HDL2 than with HDL1 or HDLc. The results of competitive studies between LDL and HDL subfractions indicate that adrenal cells take up cholesterol from HDL2 and LDL by separate mechanisms but that LDL and HDL containing apolipoprotein E share the same uptake processes. In experiments with various concentrations of HDLc or HDL without apolipoprotein E, the adrenal cells displayed a higher affinity for rat HDLc than for rat HDL without apolipoprotein E. However, HDL without apolipoprotein E produced a higher enhancement of the cholesterol cell content and was 3-fold more effective in stimulating 21-hydroxylated steroid production than rat HDLc. Although these findings suggest a participation of HDL with apolipoprotein E in the HDL interaction with rat adrenal cells, the predominant effect on these cells is devoluted to HDL containing mainly apolipoprotein A.

Adrenal Cortex

The prevalence of autoantibodies during third-trimester pregnancy complicated by hypertension or idiopathic fetal growth retardation.

Lupus anticoagulant, anticardiolipin, antinuclear, anti-deoxyribonucleic acid, antithyroglobulin, and antithyroid microsomal antibodies were assayed during third-trimester pregnancy (100 normal, 100 with complications). In spite of a normal activated partial thromboplastin time in all instances, lupus anticoagulant was further investigated by three additional procedures: tissue thromboplastin inhibition time, platelet neutralization procedure, and cephalin neutralization test. The prevalence of autoantibodies in pregnancies with hypertension reaches 16% (four with lupus anticoagulant, two with anticardiolipin, and two with antithyroid microsomal antibodies), which is significantly greater than that for idiopathic fetal growth retardation (2%) (one with lupus anticoagulant antibodies) and normal pregnancies (3%) (two with antithyroglobulin and one with autithyroid microsomal antibodies) (p less than 0.01). Autoantibodies were equally distributed between patients with gestational hypertension and those with preeclampsia. When compared with the 42 patients with hypertension and no autoantibodies, the eight patients with autoantibody had a more frequent history of fetal growth retardation (p less than 0.05), but there was no difference in the severity of hypertension, the frequency of obstetric complications, or the outcome of pregnancy. They did not require any specific treatment.

Autoantibodies

[Prevention of complications of severe arterial hypertension in pregnancy using platelet antiaggregants].

A prospective study conducted between January, 1985 and September, 1987 involved 60 pregnant women who had previously suffered from hypertension in pregnancy with or without foetal and maternal complications. Thirty women received aspirin 250 mg every other day and dipyridamole 300 mg per day, starting from the 3rd month of pregnancy (group I); 30 women were examined regularly from the onset of pregnancy and received the conventional symptomatic treatment of complications that occurred (group II). Women in these two groups were similar in age, parity and previous obstetrical complications. Twenty-five women of group I had a perfectly normal pregnancy, as against 5 women of group II (P less than 0.001). Hypertension and/or proteinuria were observed in 5 women of group I and 15 of group II (NS). The 13 severe complications recorded (foetal death, eclampsia, retroplacental haematoma) occurred exclusively in women of group II. The duration of pregnancy and weight of the newborn were significantly greater in group I than in group II. Thus, antiplatelets appear to have an uncertain preventive effect on hypertension of pregnancy and a much more obvious prophylactic effect on major foetal and maternal complications.

Adult

A serum-free medium with or without a carrier protein supports the growth of the Y-1 mouse adrenocortical cell line and its steroidogenic function.

The development of a method for the serum-free culture of the Y-1 mouse adrenocortical tumor cell line has permitted a detailed search for factors regulating cellular growth and steroidogenesis. The serum-free medium (SFM) was made of Ham's F10 basal medium supplemented with free fatty acids adsorbed on albumin. The SFM complemented with calcium, arachidonic acid and cholesterol, i.e. SFM-S, induced cell proliferation to a density at confluency higher than that obtained with 1% serum-supplemented medium (1%-SSM) and allowed to sustain cell growth for more than six passages. When albumin was replaced by a dextran polymer (Mr = 2 x 10(6)) used as a carrier of lipids instead of albumin (which resulted in a serum-free and protein-free medium, SPFM), the cell number was 75% of that observed with the SFM-S. The addition to SPFM of beta-globulin alone or combined with insulin caused a 2- or 3-fold increase in the final cell density, respectively. The ability of the Y-1 cell line to produce steroids in response to ACTH was found to be higher in SFM-S or SPFM than in 1%-SSM. Furthermore, the addition of beta-globulin to SPFM stimulated steroid hormone biosynthesis with a marked increase in 11 beta-hydroxylated steroid production. These studies demonstrate that the use of a defined mixture of nutriments and of few growth factors permits to sustain not only the cellular proliferation of the Y-1 cell line but also its differentiated function of ACTH-induced steroidogenesis.

Adrenal Cortex

Induction of corticosteroid biosynthetic pathway by ACTH and high-density lipoprotein in newborn rat adrenocortical cells cultured in serum-free medium.

In order to investigate the role of rat high-density lipoprotein (HDL) on adrenal cholesterol accumulation and steroidogenic pathways (corticosteroid, i.e., 21-hydroxysteroid biosynthesis and reductive metabolism of progesterone), newborn rat adrenal cells cultured in serum-free medium were used. Incubation of [4-14C]cholesterol-HDL in serum-free medium compared to those in medium with lipoprotein-deficient serum, in serum-free medium with ACTH compared to those without ACTH, both showed an increase of labelled cholesterol in cells and of labelled 21-hydroxysteroids excreted in medium. Substitution of serum-supplemented medium by serum-free and cholesterol-free medium led to a deep decrease of ACTH-induced steroid biosynthesis with a predominance of 20 alpha-reduced steroids; addition of HDL restored the corticosteroid biosynthesis and decreased the reductive metabolism. Addition of increased concentrations of HDL (7-150 micrograms cholesterol/ml) enhanced, in a saturable fashion, the total cholesterol uptake and the corticosteroid biosynthesis. The total cholesterol accumulation in cells exceeded by 4-fold the steroid production at saturation. The ratio between the two steroidogenic pathways increased up to 40 at saturation in favor of corticosteroids. These results suggest that HDL is at least partly internalized and that probably its constituents contribute greatly to the control of the two different steroidogenic pathways.

Adrenal Cortex

Expression of ACTH-induced corticosteroid biosynthesis in newborn rat adrenocortical cells cultured in serum-free and carrier protein-free medium containing a cholesterol-alpha-cyclodextrin complex.

Newborn rat adrenocortical cells were successfully cultured in a serum-free carrier protein-free medium (SPFM) by using alpha-cyclodextrin as a cholesterol carrier and have expressed corticosteroid biosynthesis in this medium. A stable inclusion complex of cholesterol-alpha-cyclodextrin with a molar ratio of almost 1 was obtained for a 5 X 10(-5) mol/1 alpha-cyclodextrin concentration. Cell cultures incubated with [4-14C] cholesterol-alpha-cyclodextrin in SPFM produced, under ACTH stimulation, various 14C labeled steroids with a predominance of corticosterone and 18-hydroxy-11-deoxycorticosterone. As measured by gas chromatography and mass spectrometry, the ratio between corticosteroids (21-hydroxylated steroids) and 20 alpha-reduced steroids produced in SPFM with cholesterol-alpha-cyclodextrin was equal to 1.8. This corresponds to a value of 3.6 times higher than that found in the serum-free medium with cholesterol-albumin. Consequently, the chemically defined SPFM with cholesterol-alpha-cyclodextrin used in this study is more suitable for corticosteroidogenesis by adrenal cells in culture than a serum-free medium with cholesterol-albumin.

Adrenal Cortex

Role of albumin for the cholesterol transport and on the steroidogenic pathways in serum-free medium newborn rat adrenocortical cell cultures.

[3,4-13C]cholesterol-albumin complex incubated in serum-free medium allowed to evaluate quantitatively the transfer of cholesterol in newborn rat adrenocortical cultured cells, its accumulation as free cholesterol or cholesterol esters and its transformation into steroids which were also originated (47%) from intracellular unlabelled cholesterol. Increasing concentrations of albumin up to 5 g/l enhanced the production of total steroids but in the meantime decreased the 21-hydroxylated steroid fraction. Internalization of albumin shown by using [methyl-14C]methylated-albumin as a tracer accounted only for a minor part in the cholesterol uptake but strikingly affected the steroidogenic pathways by favoring the reductive metabolism of progesterone over the corticosteroid biosynthesis.

Adrenal Cortex