High cholesterol diet results in increased expression of interleukin-6 and caspase-1 in the brain of apolipoprotein E knockout and wild type mice

Inflammation in the central nervous system is an early hallmark of many neurodegenerative diseases including Alzheimer's disease (AD). Recently, increasing evidence suggests that hypercholesterolemia during midlife and abnormalities in the cholesterol metabolism could have an important role in the pathogenesis of AD. In the present study, we have evaluated the effect of high cholesterol (HC) diet on the expression of interleukin-6 (IL-6), a cytokine involved in neurodegeneration, and caspase-1, that is responsible for the cleavage of the precursors of interleukin-1 beta (IL-1 beta) and interleukin-18 (IL-18) in the brain of apolipoprotein E (Apo E) knock-out (KO) and wild type (WT) mice. The density of IL-6-positive cells was increased in the hippocampus (p<0.0001) and the dorsal part of the cortex (p<0.001) of KO and WT mice on HC diet (KOHC and WTHC mice, respectively) compared to KO and WT mice on ND (KOND and WTND mice, respectively). KOHC mice had increased caspase-1 positive cells and staining intensity in the hippocampus in comparison with WTHC mice (p<0.01). In the hippocampus, the density of caspase-1 positive cells was also higher in KOHC compared to KOND mice (p<0.05) and KOHC compared with WTHC mice (p<0.01). There was a major increase in caspase-1 immunoreactivity and cell density in both the dosal part of the cortex (p<0.001) and the lateral part of the cortex (p<0.005) in KO and WT mice on HC diet compared to ND. The findings of the present study indicate that chronic exposure to HC diet increases the expression of the two important inflammatory mediators IL-6 and caspase-1 in the brain of KO and WT mice. In the case of caspase-1, we report a major difference in the effect of HC diet on the KO mice compared to WT mice in the hippocampus. Increased expression of inflammatory mediators involved in neurodegeneration could be a potential mechanism by which hypercholesterolemia and HC diet increase the risk of AD.     

Non-Hodgkin's malignant lymphoma of the peripheral nervous system: clinicopathological correlations in ten patients

INTRODUCTION: Identifying tumor infiltration or compression in patients with non-Hodgkin's malignant lymphoma presenting peripheral neuropathy can be a difficult task. METHODS: We collected a series of patients with peripheral neuropathy with demonstrated lymphomatous infiltration or compression managed between October 1977 and October 2001 to search for clinico-pathological correlations. RESULTS: Ten cases were reviewed. Neurological manifestations were the inaugural symptom of the disease in 7 patients. Clinical presentations included 5 focal (3 cranial nerve palsies, 2 brachial radiculopathies) and 5 diffuse neuropathies (3 polyradiculoneuropathies, 1 polyneuropathy and 1 mononeuritis multiplex). The mechanisms of peripheral nerve involvement were classified into lymphomatous meningoradiculitis (5 cases), involvement of cranial nerves or spinal roots in their extraneuraxial course (3 cases) and infiltration of distal peripheral nerves (2 cases). Four long lasting survivals after treatment were observed. CONCLUSIONS: Prognosis depends much more on the haematological disease than on the neurological symptoms or tumor location.     

1H MRS studies in the Finnish boron neutron capture therapy project: detection of 10B-carrier, L-p-boronophenylalanine-fructose

This article summarizes the current status of 1H MRS in detecting and quantifying a boron neutron capture therapy (BNCT) boron carrier, L-p-boronophenylalanine-fructose (BPA-F) in vivo in the Finnish BNCT project. The applicability of 1H MRS to detect BPA-F is evaluated and discussed in a typical situation with a blood containing resection cavity within the gross tumour volume (GTV). 1H MRS is not an ideal method to study BPA concentration in GTV with blood in recent resection cavity. For an optimal identification of BPA signals in the in vivo 1H MR spectrum, both pre- and post-infusion 1H MRS should be performed. The post-infusion spectroscopy studies should be scheduled either prior to or, less optimally, immediately after the BNCT. The pre-BNCT MRS is necessary in order to utilise the MRS results in the actual dose planning.     

Tobacco: a potential inductor of lipid peroxidation of the human spermatozoon membrane?

OBJECTIVE: To determine the membrane lipid peroxidation of human spermatozoon in a cohort of smokers in comparison of never-smokers. MATERIALS AND METHODS: Malondialdehyde (MDA), a stable product of the membrane lipid peroxidation, was assessed in 25 smokers and in 17 never-smokers. In parallel, an evaluation of sperm characteristics was realized for all the studied patients. RESULTS: For the first time, between smokers and never-smokers, a significative increase of MDA concentrations was found by the U-Mann and Whitney test (0.118 +/- 0.176 vs 0.0392 +/- 0.0117 nmol/10(6) spermatozoa), a decrease of the forward motility (grade A), (18 +/- 8 vs 25 +/- 8%) and total sperm count (265.56 +/- 186.96 x 10(6) vs 399.30 +/- 322.23 x10(6)), and also an increase of tapering heads (6 +/- 4 vs 2 +/- 2%) or morphological stress pattern cells (39 +/- 6 vs 24 +/- 5%). In the smokers group, negative significative correlations were found by the non-parametric Spearman test between the MDA concentrations and the sperm count per mL (r=-0.767, p<0.001), the total sperm count (r=-0.656, p<0.001) and the percentage of normal morphology (r=-0.644, p<0.001). CONCLUSIONS: Given of deleterious effects of tobacco in a large panel of human cells and specially on the male gametes, the increase of spermatozoon membrane MDA concentrations and the sperm abnormalities found in the group of smokers may be linked to cigarette smoking.     

Viral transmission and medically assisted procreation: the Herpesviridae case

Procreation with sperm donation is at present achieved by insemination either in the uterus or in vitro, always from ejaculated and washed spermatozoa. Then, the infectious risk only exists if the donor sperm is capable of transporting the virus or its DNA, either by adhesion or by integration. With CMV, HSV1 and HSV2, medically assisted procreation in couples (AI or IVF-ET) does not increase the risk of viral contamination as compared with natural procreation, except possibly the cases of surgical procedure to pick up testicular sperm to be used in ICSI. Animal experiments show that, even if viral material is introduced in the oocyte, it may be eliminated from the embryo, at least for CMV.     

Critical period for styrene ototoxicity in the rat

The current experiments were undertaken to determine whether or not styrene-induced hearing loss in the rat depends more on the existence of a critical period between 14 and 21 weeks of age than on body weight. For these purposes, two experiments were carried out with mature Long-Evans rats. In the first experiment, two groups of 5-month old rats, but having different body weight (slim: 314 g vs. fat: 415 g) were exposed to 700 ppm styrene for 4 consecutive weeks, 5 days per week, 6 hours per day. In the second experiment, two groups of rats having the same weight: 345 g, but different ages (14- vs. 21- week old) were exposed to styrene in strictly identical experimental conditions. Auditory sensitivity was tested by recording evoked potentials from the inferior colliculus. Surface preparations of the organ of Corti were also performed to complete the investigation. At the end of the six week recovery period following the styrene exposure, a 7 dB permanent threshold shift (PTS) was obtained with the same age animals regardless of the body weight. Consequently, weight was not a major factor in styrene-induced hearing loss. Age was a more critical factor in determining higher sensitivity to styrene. Indeed, the three months old group had 23.5 dB PTS, whereas the five months old group had only a 7.7 dB PTS at 16 kHz. Thus, a 15 dB difference of PTS was obtained between the rats having the same weight but different age. While the weight does not play a major role in styrene ototoxicity, there is a critical period whose duration lasts more than three months and for which the susceptibility to styrene is enhanced.     

Bladder cancer: worse survival in women from deprived areas

In a case-note review of 120 women and 227 men presenting with muscle-invasive bladder tumours in 1998, survival was worse for women in 3 years of follow-up, with the greatest difference, of 19.9%, at 6 months. For more deprived women, 6-month survival was 52.3%, and 32 (37.2%) presented with advanced disease, compared with 73.5%, and three (8.8%) for less deprived women.     

Chemosensitivity and radiosensitivity profiles of four new human epithelial ovarian cancer cell lines exhibiting genetic alterations in BRCA2, TGFbeta-RII, KRAS2, TP53 and/or CDNK2A

To address the cellular basis for the response to ovarian cancer treatment, we characterized the chemosensitivity and radiosensitivity of four human epithelial ovarian cancer cell lines that harbor different genetic alterations. The TOV-21G, TOV-81D, OV-90, and TOV-112D cell lines were derived from ovarian tumors (TOV) or ascites (OV) from chemotherapy- and radiotherapy-naive patients and were characterized by their mutation spectrum of BRCA2, TGF-RII, KRAS2, TP53, and CDKN2A. Cells were monitored for survival following exposure at various concentrations to different cytotoxic agents including cisplatin, camptothecin or paclitaxel or to different doses of -irradiation. At the lowest doses, the TGF-RII-mutated and KRAS2-mutated cell line, TOV-21G, and the BRCA2-mutated cell line, TOV-81D, demonstrated a significantly higher sensitivity to cisplatin and -irradiation than the TP53-mutated cell lines, TOV-112D and OV-90. At higher doses, differences between the TP53-mutated lines were observed with TOV-112D being less sensitive to cisplatin than OV-90 that also harbors a CDNK2A mutation. All cell lines were similarly sensitive to high doses of -irradiation. In contrast, sensitivity to camptothecin or paclitaxel was not significantly different between all cell lines, irrespective of the mutation status of BRCA1, BRCA2, TGF-RII, KRAS2, TP53, and CDKN2A. The observed responses to treatment are consistent with the current knowledge concerning BRCA2, TGF-RII, KRAS2, TP53, and/or CDKN2A aberrant function.The first and second authors contributed equally to this work.     

Nail disease due to Scytalidium in Martinique (French West Indies)

INTRODUCTION: Scytalidium is an endemic mold in tropical and subtropial areas. Our purpose was to study the prevalence and clinical and epidemiological features of onychomycoses due to Scytalidium in Martinique (French West Indies). PATIENTS AND METHODS: We performed a prospective study on 106 patients (46 men and 60 women) with clinical onychomycosis, in the dermatological department of the Centre Hospitalier Universitaire of Fort-de-France. All patients underwent mycological sampling and were divided into two groups depending on the presence or not of Scytalidium. Age, sex, localization, clinical aspects, time of duration and environmental factors (place of residence, garden, animals, bare foot walk, immunodepression) were compared between the two groups using chi2, Fisher and Student's t test. Ten control volonteers without clinical onycomycosis underwent mycological sampling. RESULTS: Onychomycosis due to scytalidium represented 42 p. 100 of patients (Scytalidium hyalinum in 91 p. 100 of cases) and 56 p. 100 after elimination of patients with negative results. Medium age was significantly higher in Scytalidium group (62 versus 54 years; p<0.02). Toe nail was involved in 95 p. 100 of patients (big toe nail in 77 p. 100). Sole involvement was more frequent in Scytalidium group (47 p. 100 versus 14 p. 100; p<0.001). Sampling of controls showed scytalidium in one case. DISCUSSION: Our study confirmed the endemicity of Scytalidium hyalinum in Martinique and the frequence of sole involvement. Presence of Scytalidium without clinical features in one control is of epidemiological interest, and may explain the frequence of the disease.