Modulation of lipid peroxidation in human spermatozoa and human prostate by prostatic inhibin.

Loss of sperm motility as a result of the production of hydrogen peroxide by lipid peroxidation is regulated by as yet unidentified prostatic factor(s). Inhibinlike peptide of prostatic origin isolated from human seminal plasma, with a molecular size of about 10,400 daltons, was studied for its effect on ascorbate-induced lipid peroxidation in human spermatozoa. Dose-related suppression of lipid peroxidation was observed at dose levels of 0.25, 0.5, and 1.0 micrograms. The data suggest that inhibinlike peptide could be one of the factors involved in the regulation of lipid peroxidation and thereby of sperm motility. Inhibinlike peptide also exhibited local action in both normal and benign hyperplastic human prostate tissue by enhancing the rate of lipid peroxidation. These findings have implications in the pathophysiology of the prostate.     

Decreased peroxidative potential in rat brain microsomal fractions during ageing

Rough and smooth microsomes of brain in senescent rats showed less sensitivity to ascorbate-, NADPH- and cumene hydroperoxide-induced peroxidative damage compared with those of young adults. The observed decrease in peroxidative potential in senescent rats seemed to be due to decrease in the substrate for peroxidation in the form of phospholipids and increase in the level of antioxidants such as reduced glutathione and superoxide dismutase.     

Genomic imprinting: potential function and mechanisms revealed by the Prader-Willi and Angelman syndromes

The Prader-Willi (PWS) and Angelman (AS) syndromes are two clinically distinct syndromes which result from lack of expression of imprinted genes within chromosome 15q11-q13. These two syndromes result from 15q11-q13 deletions, chromosome 15 uniparental disomy (UPD), imprinting centre mutations and, for AS, probable mutations in a single gene. The differential phenotype results from a paternal genetic deficiency in PWS patients and a maternal genetic deficiency in AS patients. Within 15q11-q13, four genes (SNRPN, IPW, ZNF127, FNZ127) and two expressed sequence tags (PAR1 and PAR5) have been found to be expressed only from the paternally inherited chromosome, and therefore all must be considered candidate genes involved in the pathogenesis of PWS. A candidate AS gene (UBE3A) has very recently been identified. The mechanisms of imprinted gene expression are not yet understood, but it is clear that DNA methylation is involved in both somatic cell expression and inheritance of the imprint. The presence of DNA methylation imprints that distinguish the paternally and maternally inherited alleles is a common characteristic of all known imprinted genes which have been studied extensively, including SNRPN and ZNF127. Recently, several PWS and AS patients have been found that have microdeletions in a region upstream of the SNRPN gene referred to as the imprinting centre, or IC. Paternal IC deletions in PWS patients and maternal IC deletions in AS patients result in uniparental DNA methylation and uniparental gene expression at biparentally inherited loci. The IC is a novel genetic element which controls initial resetting of the parental imprint in the germline for all imprinted gene expression over a 1.5-2.5 Mb region within chromosome 15q11-q13.      

Fertility regulating and immunotherapeutic vaccines reaching human trials stage

The progress and current status of vaccines which induce antibodiesagainst human chorionic gonadotrophin (HCG) and luteinizinghormone-releasing hormone (LHRH) are reviewed. Three vaccinesdevised against HCG have undergone phase I clinical trials documentingtheir safety, and reversibility. One of these, the heterospeciesdimer (HSD)-HCG vaccine has also completed phase II efficacytrials in sexually active women of proven fertility. Immunizationwith the vaccine prevents pregnancy, as long as the antibodytitres remain =" BORDER="0">50 ng/ml HCG bioneutralization capacity.There is no disturbance of menstrual regularity and women continueto ovulate normally. The antibody response is predominantlyagainst an epitope in the core part of ß-HCG. Fertilityis regained at titres <35 ng. These observations have laidthe scientific foundations of a birth control vaccine. Researchsuggests the feasibility of making a cost-effective recombinantvaccine. The carriers tetanus toxoid (TT) and diptheria toxoid(DT) can be advantageously replaced by peptide determinantsrecognizing T, not B cells. In addition to optional fertilitycontrol, HCG vaccines may have tumour growth inhibition potentialin lung cancers which produce HCG. The vaccine against LHRHcan be used in both males and females. As it is a structurallyconserved molecule, the same vaccine is applicable to both animalsand humans. Antibodies against LHRH block the generation ofgametes and sex steroids, with the result that the vaccine canbe used for fertility control (domestic pets, prolongation oflactation amenorrhoea); as well as for sex hormone-dependentcancers. Phase I/phase II clinical trials have been conductedwith the LHRH vaccine in advanced metastazing carcinoma of prostatepatients with encouraging results. Bioeffective monoclonal antibodieshave been developed against both LHRH and HCG. These can be`humanized' and produced cost-effectively in bacteria and plants,thus paving the way for passive use of such antibodies for immunotherapyof cancers and fertility control.     

High-intensity focused ultrasound ablation as a bridging therapy for hepatocellular carcinoma patients awaiting liver transplantation

The scarcity of liver grafts in Asia leads to a significant dropout of patients from liver transplant waiting lists, particularly patients with hepatocellular carcinoma and a low model for end-stage liver disease score. In order to reduce dropping out, different bridging therapies are employed. We report the use of high-intensity focused ultrasound ablation as a bridging therapy for a patient with hepatocellular carcinoma of stage two and an extremely low platelet count (20×10⁹/L). The ablation was successful. Blood tests showed that his liver function was similar before and after the treatment. No adhesion was encountered in the liver transplantation performed six months later.     

Oral manifestations of inflammatory bowel disease: a review based on the observation of six cases

Inflammatory bowel disease (IBD) comprises two chronic, tissue‐destructive, clinical entities: Crohn's disease (CD) and ulcerative colitis (UC), both immunologically based. Bowel symptoms are predominant, but extra‐intestinal complications may occur, including involvement of the oral cavity. Oral involvement during IBD includes several types of lesions: the most common are aphthae; uncommon lesions include, among others, pyostomatitis vegetans and granulomatous lesions of CD. Starting with a presentation of six patients with oral manifestations, which were crucial for the final diagnosis of IBD, a review on the subject is presented. Oral involvement in IBD may be previous or simultaneous to the gastrointestinal symptoms. However, in the majority of cases, bowel disease precedes the onset of oral lesions by months or years. In many patients, the intestinal symptoms may be minimal and can go undetected; thus, most authors believe that the bowel must be thoroughly examined in all patients with suspected IBD even in the absence of specific symptoms. Usually, the clinical course of oral lesions is parallel to the activity of IBD; therefore, oral manifestations are a good cutaneous marker of IBD.