In this prospective study we performed repeated evaluations of thyroid status in patients undergoing treatment with different preparations of recombinant interferons (IFNs), in order to identify early markers of thyroid dysfunction. Moreover, we aimed to investigate whether the development of thyroid dysfunction was related to the appearance of thyroid autoimmunity. Our study included 51 consecutive patients without pre-existing thyroid disease, admitted to our hospital for Hepatitis C virus (HCV)-related chronic hepatitis. Thirty-six patients (Gr. A) were treated with IFN-alpha 2b plus ribavirin (RIBA), whereas 15 patients (Gr. B) underwent treatment with IFN-alphacon-1 (CIFN) plus RIBA. Thyroid autoimmunity and function were prospectively evaluated before, every month during treatment and for 6 months after IFN withdrawal. At study entry, all patients were euthyroid and negative for thyroid autoantibodies. In Gr. A, 10 patients developed thyroid autoimmunity after a median period of 3 months (range: 1-6) treatment with IFN-alpha+RIBA. At the time of appearance of thyroid autoantibodies, 4 patients developed destructive thyrotoxicosis (overt in one case, subclinical in 3 cases), while other 4 patients showed a high reduction of serum TSH levels (median decrease: -75.7%, range: -61.9- -84.2), which reached the low values of normal range. After a median period of 2 months (range: 1-3) from these biochemical abnormalities, 6 patients continuing antiviral treatment developed hypothyroidism (overt in 3 cases and subclinical in the other 3). In Gr. B, 5 patients developed thyroid autoimmunity after a median period of 3 months (range: 2-10) of treatment with CIFN+RIBA. Soon after the appearance of thyroid autoantibodies, all patients developed an overt thyrotoxicosis (with hyperthyroidism in 2 cases). Antiviral treatment was discontinued in all 5 cases. Thereafter, thyroid function recovered spontaneously without significant modifications of serum TGAb and TPOAb levels until the end of the study. In conclusion our prospective study demonstrated that: 1) the appearance of thyroid autoantibodies during treatment with IFN was accompanied in most cases by the occurrence of a destructive process in the thyroid gland; 2) The clinical expression of destructive thyroiditis was more evident in patients treated with CIFN than that in patients treated with IFN; 3) The thyroid clinical outcome of these patients was strictly correlated to the continuation of cytokine treatment.

Adult↗

PubMedDate not supplied

Microsomal oxidation of N,N-diethylformamide and its effect on P450-dependent monooxygenases in rat liver.

N,N-Diethylformamide (DEF) is a hepatotoxic polar solvent in which metabolism has not been investigated. In this study we examined the following: (a) the oxidative metabolism of DEF using both liver microsomes from rats pretreated with selected P450 inducers and purified P450 enzyme (2B1, 2E1, 2C11); and (b) the effect of administration of DEF and its metabolite, the monoethylformamide (MEF), on induction and/or inhibition of the P450 isoforms in rats. DEF was deethylated by microsomal P450-dependent oxidation forming acetaldehyde and MEF according to Michaelis-Menten kinetic parameters. Microsomes from rats pretreated with acetone and pyrazole (selective P4502E1 inducers) or rats pretreated with dexamethasone and 200 mg/kg DEF were able to deethylate DEF in a biphasic manner, showing a low Km component with a Vmax of about 0.2 nmol/(min.mg of protein) and a Km between 70 microM and 250 microM. The low Km component was not present in control microsomes or in microsomes from rats treated with phenobarbital, beta-naphthoflavone, or clofibrate, where linear Kinetics were observed. The use of purified P4502E1 and 2C11 in a reconstituted system showed that 2E1, which oxidized DEF with a Vmax of 4.5 nmol/(min.nmol of P450) and a Km of 0.7 mM, can partially account for the low Km DEF deethylase, whereas 2C11, which oxidized DEF with a Vmax of 4.8 nmol/(min.nmol of P450) and a Km of 17 mM, might be the high Km deethylase. The purified 2B1 was barely able to deethylate DEF. A confirmation of the role of 2E1 in DEF metabolism was obtained by using various selective inhibitors of P450 isoforms and immunoprecipitation experiments with anti P4502E1 IgG. The low Km component of DEF deethylation in acetoneor pyrazole-induced microsomes was strongly inhibited (approximately 90%) by diethyldithiocarbamate, 4-methylpyrazole, and anti-2E1 IgG, but in 200 mg/kg DEF-induced microsomes the inhibition was partial, suggesting that other P450(s) may be involved. Administration of DEF 200 mg/kg ip for 4 days induced hepatic microsomal P4502E1-dependent aniline hydroxylase, P4502B1/2-linked pentoxyresorufin O-depentylase, 16 beta-testosterone hydroxylase P4503A1/2-associated erythromycin N-demethylase, and 6 beta-testosterone hydroxylase. Alternatively, the same dose regimen of MEF induced only the aniline hydroxylase and depressed the 3A1/2-linked activities. Immunoblot experiments verified these data. These findings indicate that DEF, at low concentrations, is predominantly oxidized by P4502E1 and that this enzyme may be induced in rodents by repeated MEF or DEF treatment, thereby increasing their own metabolism and potentially their cytotoxicity through the formation of ethyl isocyanate.

Animals↗

PubMedDate not supplied

Mitochondrial DNA variability in Grauer's gorillas of Kahuzi-Biega National Park.

Eastern lowland gorillas (Gorilla gorilla graueri) are the least studied of the three gorilla subspecies; particularly at the molecular level. We sequenced an internal region of the mitochondrial DNA cytochrome oxidase subunit II (COII) region and a hypervariable portion of the mitochondrial DNA control region (D-loop) from wild gorillas in both the montane and lowland habitats of Kahuzl-Blega National Park, Democratic Republic of Congo. All individuals (n = 38) were identical at the COII region; this sequence indicates that diagnostic sites previously suggested for gorilla subspecies may be valid. Low variability was found within the D-loop region from a subset of the individuals (n = 15) sequenced for COII. Haplotype frequencies differed between the two habitats, suggesting a level of population subdivision that may have demographic consequences. These results also support the distinction of two distinct clades of gorillas comprised of western populations (G. g. gorilla) and eastern populations (G. g. graueri and G. g. beringei). Future management of Kahuzi-Biega National Park should ensure that sufficient habitat remains to prevent further genetic isolation of gorillas in the montane section of the park.

Animals↗

PubMedDate not supplied

Optical coherence tomography findings in diabetic macular edema before and after vitrectomy.

BACKGROUND AND OBJECTIVE: To assess the role of optical coherence tomography (OCT) in the evaluation and follow-up after vitrectomy for diabetic macular edema. MATERIALS AND METHODS: The 18 eyes of 12 patients affected by presumed diabetic vitreous-induced macular edema underwent biomicroscopy with a Goldmann contact lens, fluorescein angiography, and OCT. RESULTS: OCT revealed two patterns of edema. The first group (15 eyes) was characterized by widespread thickening of the neurosensory retina with an increased nonhomogeneous reflectivity of the inner retinal layers; cystoid-like spaces of absent or reduced reflectivity in the neurosensory retina were also present. In the second group (3 eyes), a cystoid macular edema with a dome-shaped foveal profile because of a markedly increased retinal thickness in the foveal region was observed. The disappearance of the physiologic foveal profile was always seen. Biomicroscopy revealed an increased reflex of the inner limiting membrane in the first group and minimal alterations in the second one. Four patients (7 eyes) underwent vitrectomy with posterior hyaloid removal. In 5 eyes, the patients experienced a visual improvement greater than two Snellen lines. The restoration of the normal foveal profile and the reduction of the retinal thickness on the OCT were evident in all cases one month after surgery. CONCLUSION: OCT appears to be a useful tool in the diagnosis and management of diabetic macular edema and in the monitoring of the morphological changes after vitrectomy.

Aged↗

PubMedDate not supplied

Symmetry of healthy adult feet: role of orthostatic footprint at computerized baropodometry and of digital formula.

Morphological aspects of orthostatic footprints (anterior heel, isthmus, posterior heel), using computerized baropodometry and of the digital formula were studied in 97 subjects (37 males, 60 females; median age: 20.9+/-1.56) at the Medical School of Palermo, Italy. The aim of this study was to contribute to our knowledge of the bilateral symmetry and asymmetry of the human feet in ethnically similar groups. We evaluated the length of the footprints (FL) and the widths of the anterior heel (AHW), isthmus (IW), and the posterior heel (PHW). Values were compared in the left and right feet of each subjects. The general morphology of the footprints was considered to determine bilateral correspondence or divergence. We also evaluated the digital formula to verify any bilateral correspondence. The linear measurements of the footprints did not show any particular bilateral conformity. The general morphology of the footprint showed bilateral correspondence in 76 subjects (78%): in 21 subjects (22%) it did not show any. Typological results of the bilateral orthostatic footprints showed normalfootprints in 54 subjects (55.5%): the isthmus included 1/3 to 2/3 of the AHW. Hollow footprints were found in 20 subjects (20.5%): the isthmus was less than 1/3 of the AHW. At clinical examination, using the digital formula, we found that Egyptian foot (1 degree > 2 degrees) was the most frequent (68%). The standard foot (1 degree = 2 degrees) and the Greek foot (1 degree < 2 degrees) were both present in 16% of the feet examined. Seventy-nine subjects (82%) presented bilaterally correspondent digital formulas: 1 degree > 2 degrees in 59 subjects (62%), 1 degree = 2 degrees in 9 subjects (9%), and 1 degree < 2 degrees in 11 (11%). While comparison of the bilateral linear measurements studied showed that there was primarily no bilateral correspondence, the morphological aspects of the footprints and of the digital formulas showed that bilateral correspondence was prevalent.

Adult↗

PubMedDate not supplied

[Plasma concentrations of complement components C3, C4, and C3PA in juvenile nephropathies].

Complement profiles in children suffering for nephropathy have been investigated. The approach has proved useful in differentiating distinct nosologic entities. Plasma C3 and, to a lesser extent, C4 levels were found to be markedly reduced in glomerulonephritis and significantly increased in nephrotic syndrome. Although in both conditions plasma C3PA concentration ranges normally, additional data are request before assuming that alternate pathway is not involved. The extensive serial study of complement profiles should be widely adopted by clinicians managing nephropatic patients.

Acute Disease↗