54 research outputs found
Aromatase inhibitors in men: effects and therapeutic options
Aromatase inhibitors effectively delay epiphysial maturation in boys and improve testosterone levels in adult men Therefore, aromatase inhibitors may be used to increase adult height in boys with gonadotropin-independent precocious puberty, idiopathic short stature and constitutional delay of puberty. Long-term efficacy and safety of the use of aromatase inhibitors has not yet been established in males, however, and their routine use is therefore not yet recommended
Determinants of Plasma Androgen and Estrogen Levels in Men
__Abstract__
The steroid hormone testosterone is responsible for the development of the primary and
secondary male sex characteristics such as male pattern hair growth, deepening of the voice
and increased lean body mass. Testosterone is produced in the testicular Leydig cells in
response to stimulation by pituitary derived luteinizing hormone (LH). In its turn the pituitary
LH secretion is regulated by the hypothalamus. Testosterone will feed back onto the pituitary
and hypothalamus thereby allowing the hypothalamo-pituitary-testicular (HPG) axis to
maintain the plasma testosterone concentration within close limits. The serum testosterone
concentration is considered normal when within the reference range as supplied by the
laboratory. The lower limit of this reference range represents the 2.5 percentile of testosterone
levels of a group of apparently healthy men. However, testosterone levels may vary
considerably between individuals.
Older men may have signs and symptoms reminiscent oftestosterone deficiency such as lack
of libido, erectile dysfunction and lower bone and lean body mass. In older men the mean
testosterone concentration in blood is lower compared to young men. The question is whether
the above-mentioned symptoms truly represent testosterone deficiency. For an adequate
answer to this question a better understanding of the determinants ofthe serum testosterone
level in men is necessary in order to better differentiate between normal and abnormal levels
in a specific individual.
In the body testosterone is converted to estradiol. In the past ten years it has become evident
that estradiol is responsible for a number of the effects formerly attributed to testosterone.
Estradiol has an important role in gaining and maintaining bone mass, closing of the
epiphyses and the feedback on gonadotropin release by the pituitary. Since estradiol may be a
determinant of the circulating testosterone concentrations but may also be involved in the
development ofthe clinical syndrome associated with androgen deficiency, evaluation of
estradiol levels in men seems appropriate. However, the interpretation of estradiol levels in
men is probably even more difficult than the interpretation of testosterone concentrations.
Only little is known about the determinants of the estradiol serum concentration in men, its
interaction with testosterone and the minimal tissue level needed to prevent symptoms of
estrogen deficiency.
Therefore, the aim of the present thesis was to gain more insight into the determinants of the
testosterone and estradiol concentrations in men. This information may be helpful when
interpreting the serum testosterone and estradiol concentrations of men with symptoms
reminiscent of androgen deficiency
Enhancement of feline immunodeficiency virus infection after immunization with envelope glycoprotein subunit vaccines.
Cats were immunized three times with different recombinant feline immunodeficiency virus (FIV) candidate vaccines. Recombinant vaccinia virus (rVV)-expressed envelope glycoprotein with (vGR657) or without (vGR657 x 15) the cleavage site and an FIV envelope bacterial fusion protein (beta-Galactosidase-Env) were incorporated into immune-stimulating complexes or adjuvanted with Quil A. Although all immunized cats developed antibodies against the envelope protein, only the cats vaccinated with the rVV-expressed envelope glycoproteins developed antibodies which neutralized FIV infection of Crandell feline kidney cells. These antibodies failed to neutralize infection of thymocytes with a molecularly cloned homologous FIV. After the third immunization the cats were challenged with homologous FIV. Two weeks after challenge the cell-associated viral load proved to be significantly higher in the cats immunized with vGR657 and vGR657 x 15 than in the other cats. The cats immunized with vGR657 and vGR657 x 15 also developed antibodies against the Gag proteins more rapidly than the cats immunized with beta-Galactosidase-Env or the control cats. This suggested that immunization with rVV-expressed glycoprotein of FIV results in enhanced infectivity of FIV. It was shown that the observed enhancement could be transferred to naive cats with plasma collected at the day of challenge
A Broad Set of Different Llama Antibodies Specific for a 16 kDa Heat Shock Protein of Mycobacterium tuberculosis
Background Recombinant antibodies are powerful tools in engineering of novel diagnostics. Due to the small size and stable nature of llama antibody domains selected antibodies can serve as a detection reagent in multiplexed and sensitive assays for M. tuberculosis. Methodology/Principal Findings Antibodies for Mycobacterium tuberculosis (M. tb) recognition were raised in Alpaca, and, by phage display, recombinant variable domains of heavy-chain antibodies (VHH) binding to M. tuberculosis antigens were isolated. Two phage display selection strategies were followed: one direct selection using semi-purified protein antigen, and a depletion strategy with lysates, aiming to avoid cross-reaction to other mycobacteria. Both panning methods selected a set of binders with widely differing complementarity determining regions. Selected recombinant VHHs were produced in E. coli and shown to bind immobilized lysate in direct Enzymelinked Immunosorbent Assay (ELISA) tests and soluble antigen by surface plasmon resonance (SPR) analysis. All tested VHHs were specific for tuberculosis-causing mycobacteria (M. tuberculosis, M. bovis) and exclusively recognized an immunodominant 16 kDa heat shock protein (hsp). The highest affinity VHH had a dissociation constant (KD) of 4×10-10 M. Conclusions/Significance A broad set of different llama antibodies specific for 16 kDa heat shock protein of M. tuberculosis is available. This protein is highly stable and abundant in M. tuberculosis. The VHH that detect this protein are applied in a robust SPR sensor for identification of tuberculosis-causing mycobacteria
The Results of CHD7 Analysis in Clinically Well-Characterized Patients with Kallmann Syndrome
Item does not contain fulltextCONTEXT: Kallmann syndrome (KS) and CHARGE syndrome are rare heritable disorders in which anosmia and hypogonadotropic hypogonadism co-occur. KS is genetically heterogeneous, and there are at least eight genes involved in its pathogenesis, whereas CHARGE syndrome is caused by autosomal dominant mutations in only one gene, the CHD7 gene. Two independent studies showed that CHD7 mutations can also be found in a minority of KS patients. OBJECTIVE: We aimed to investigate whether CHD7 mutations can give rise to isolated KS or whether additional features of CHARGE syndrome always occur. DESIGN: We performed CHD7 analysis in a cohort of 36 clinically well-characterized Dutch patients with KS but without mutations in KAL1 and with known status for the KS genes with incomplete penetrance, FGFR1, PROK2, PROKR2, and FGF8. RESULTS: We identified three heterozygous CHD7 mutations. The CHD7-positive patients were carefully reexamined and were all found to have additional features of CHARGE syndrome. CONCLUSION: The yield of CHD7 analysis in patients with isolated KS seems very low but increases when additional CHARGE features are present. Therefore, we recommend performing CHD7 analysis in KS patients who have at least two additional CHARGE features or semicircular canal anomalies. Identifying a CHD7 mutation has important clinical implications for the surveillance and genetic counseling of patients
Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension
We studied the hemodynamic, neurohumoral, and biochemical effects of the
novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86
untreated patients with essential hypertension on a normal sodium diet.
According to a double-blind parallel group trial, patients were randomized
to a once-daily oral dose of the AT1 receptor antagonist (1, 25, or 100
mg) or placebo after a placebo run-in period of 3 weeks. Randomization
medication was given for 1 week. Compared with placebo, 24-hour ambulatory
blood pressure did not change with the 1-mg dose, and it fell (mean and
95% confidence interval) by 7.0 (4.2-9.8)/6.1 (3.9-8.1) mm Hg with the
25-mg dose and by 12.1 (8.1-16.2)/7.2 (4.9-9.4) mm Hg with the 100-mg
dose. Heart rate did not change during either dose. With the 25-mg dose,
the antihypertensive effect was attenuated during the second half of the
recording, and wi
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