Ultra low-dose hormone replacement therapy and bone protection in postmenopausal women

OBJECTIVES: The aim of the present study was to evaluate the effects of low doses of hormone replacement therapy (HRT) in normal young postmenopausal women. METHODS: In an open trial healthy, non-obese postmenopausal women received for 2 years a low-dose continuous combined HRT (LD-HRT) containing 1mg estradiol+0.5 mg norethisterone acetate each pill for 28 days, or 0.5 mg of 17beta-estradiol and 0.25 mg of norethisterone acetate (Ultra low dose, Ultra-LD-HRT) along with 1000 mg of calcium per day. Control group consisted of women receiving only 1000 mg of calcium per day, for 2 years. Menopausal symptoms were evaluated by the Green climacteric scale for the first 12 weeks of the study while bleeding profiles, bone mineral density (BMD) and bone turnover were assessed for 24 months. RESULTS: LD-HRT and Ultra-LD-HRT were effective in reducing menopausal clinical symptoms. In the control group, BMD significantly (P<0.05) decreased at the spine (-2.8+/-0.2%), and femoral neck (-2.8+/-0.7%). In LD-HRT treated group BMD showed a significant (P<0.05) increase at the spine (5.2+/-0.7%), and femoral neck (2.8+/-0.4%) after 24 months. In the Ultra-LD-HRT treated women spine and femoral neck BMD showed a significant (P<0.05) increase (2.0+/-0.3 and 1.8+/-0.3%, respectively) after 24 months. In these women treated with LD-HRT and Ultra-LD-HRT the BMD values were significantly (P<0.05) different from those measured in calcium-treated women. CONCLUSIONS: LD-HRT and Ultra-LD-HRT can alleviate subjective symptoms providing an effective protection against the postmenopausal decrease of BMD.     

Ultrastructure of somatostatin-immunoreactive nerve terminals in laminae I and II of the rat trigeminal subnucleus caudalis.

The morphology and distribution of somatostatin-immunoreactive synaptic boutons was studied in the rat trigeminal subnucleus caudalis using pre-embedding electron microscopic techniques. Immunoreactive terminals were found in lamina I and throughout lamina II but were more concentrated in outer lamina II. All immunoreactive terminals contained many round or pleomorphic agranular small synaptic vesicles and some large dense-cored vesicles. Lamina I terminals were all simple dome-shaped and relatively small. They established one asymmetric or slightly asymmetric synapse over a dendritic spine or a small, medium or large dendritic shaft. The large dendrites are probably derived from Waldeyer neurons. Many lamina II immunoreactive terminals were also simple dome-shaped terminals and established asymmetric synaptic contacts with one postsynaptic structure, usually a dendritic spine or a small to medium-sized dendritic shaft. However, other lamina II immunoreactive terminals were larger and displayed more complex morphology and synaptology. Complex immunoreactive terminals had scalloped or smooth contours and made synaptic contacts with more than one postsynaptic profile. In outer lamina II they sometimes constituted the central terminals of typical glomerular synaptic complexes. We conclude that many of the immunoreactive simple terminals probably originate from intrinsic somatostatin-immunoreactive interneurons while some of the more complex ones and the central glomerular terminals are likely to originate from primary afferents. These results are consistent with our accompanying light microscopic study (Alvarez and Priestley, Neuroscience 38, 343-357, 1990) which indicates that somatostatin-immunoreactive primary afferents project preferentially to outer lamina II while the lamina I somatostatin-immunoreactive plexus is likely to originate largely from laminae I and II interneurons. In addition somatostatin-immunoreactive cell bodies were found in lamina II. The heaviest immunoreactivity in these cells was in the Golgi apparatus. Also some vesicles containing dendrites were immunostained, and these were most abundant in inner lamina II. Thus, in trigeminal subnucleus caudalis, somatostatin may be derived from primary afferent synaptic boutons, interneuron synaptic boutons and interneuron dendrites. However, each of these sites probably makes a proportionately different contribution to the total amount of somatostatin released in each lamina or sublamina.     

Latex allergy in fruit-allergic patients

The purpose of this study was to investigate the prevalence of latex allergy in fruit-allergic patients, and to assess its clinical significance. Fifty-seven fruit-allergic patients and 50 non-fruit-allergic atopic patient controls were studied. All patients were questioned about conventional immediate symptoms after contact with latex products. Patients also underwent skin prick testing and determination of specific serum IgE to latex, as well as a screening test for environmental allergens. Immunologic latex sensitization occurred in 49/57 (85.9%) fruit-allergic patients, who showed a positive STP and/or CAP to latex, but in only two controls ( P <0.001). Six out of 57 (10.5%) fruit-allergic patients suffered from clinically relevant latex allergy. Symptoms included contact urticaria, angioedema, conjunctivitis, generalized urticaria, and moderate anaphylactic reactions. No control reported symptoms with latex products ( P =0.052). In all patients, clinical symptoms to fruits preceded a history of latex allergy. The fruits most associated were melon, peach, and banana. From our data, we conclude that there is a potential for allergic reactions to latex in patients with allergy to fruit. All patients with fruit allergy should be screened for individual risk of latex allergy.     

Molecular and epidemiological characteristics of blood-borne virus infections among recent immigrants in Spain

The increased immigration from developing regions to Western countries raises public health concerns related to blood-borne viruses. The prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-lymphotropic virus (HTLV) infections among recent immigrants attending several Spanish diagnostic centers in years 2002 and 2003 was examined. Genetic characterization of viral subtypes and its relationship with distinct at-risk populations was carried out. A total of 1,303 immigrants were identified. They originated in Latin America (46.9%), Sub-Saharan Africa (23.7%), Eastern Europe (9.4%), and the Maghreb (9.2%). Seroprevalence rates were as follows: HIV-1 4.2%, HBV 4.1%, HCV 2.9%, and HTLV-1 0.8%. All patients with HIV-1 non-B subtypes, HBV genotypes E and A3, and HCV genotype 4 were sub-Saharan Africans, and had been infected mainly through heterosexual contacts. In contrast, Latin American homo/bisexual men carried HIV-1 subtype B most likely acquired after their arrival to Spain. In conclusion, while Sub-Saharan Africans carry wide diverse genetic variants of blood-borne viruses, the absence of high-risk practices in most cases could limit the spread of these variants. In contrast, Latin Americans with high-risk sexual practices may be a particularly vulnerable collective to acquire blood-borne viruses in the receptor country.     

Stem cell therapy for neurodegenerative diseases: the issue of transdifferentiation

In the past few years research on stem cells has exploded as a tool to develop potential therapies to treat incurable neurodegenerative diseases. Stem cell transplantation has been effective in several animal models, but the underlying restorative mechanisms are still unknown. Several events such as cell fusion, neurotrophic factor release, endogenous stem cell proliferation, and transdifferentiation (adult cell acquisition of new unexpected identities) may explain therapeutic success, in addition to replacement of lost cells. This issue needs to be clarified further to maximize the potential for effective therapies. Preliminary stem transplantation trials have already been performed for some neurodegenerative diseases. There is no effective pharmacological treatment for amyotrophic lateral sclerosis, but recent preliminary data both in experimental and clinical settings have targeted it as an ideal candidate disease for the development of stem cell therapy in humans. This review summarizes recent advances gained in stem cell research applied to neurodegenerative diseases with a special emphasis to the criticisms put forward.     

Assisted reproductive technology and complex chromosomal rearrangements: the limits of ICSI

Complex chromosomal rearrangements are very rare events in the human population. According to our knowledge on the consequences of simple reciprocal translocations for male fertility, translocations involving three or more chromosomes are thought to lead to severe reproductive impairments in terms of meiotic disturbance or chromosomal imbalance of gametes. We report the case of a 48 year old man whose sperm count revealed either oligozoospermia (<10(3) spermatozoa/ml) or azoospermia. He was referred to the laboratory for in-vitro fertilization after intracytoplasmic sperm injection. Cytogenetic investigations showed a complex chromosomal rearrangement involving firstly a translocation between the short arm of chromosome 7 and the long arm of chromosome 13 and secondly a translocation between the short arm of the same chromosome 13 and the short arm of chromosome 9. Diagnosis was ascertained by fluorescence in-situ hybridization and staining of the nucleolar organizer regions. Theoretical study of the translocated chromosomes predicted a 'chain' configuration of the hexavalent at the pachytene stage of meiosis. In all, 32 modes of segregation were considered and only one resulted either in a normal or a balanced gamete karyotype. Genetic counselling and choice of appropriate artificial reproduction technique are discussed.      

Cell death in the ventral region of the neural retina during the early development of the chick embryo eye

The present study deals with morphologic and quantitative changes that take place in the area of cell death in the ventral part of the presumptive retinal wall of the chick embryo. These changes were followed from the optic vesicle stage until the first optic fiber fascicles leave the neural retina. Our results show that both the volume occupied by the area of cell death and the density of its pyknotic fragments undergo considerable variation during the period between Hamburger and Hamilton's (1951) stages 12 to 20. In the optic vesicle stages, cell death in the ventral wall of the vesicle was observed in 50 to 75% of the embryos studied. During stages 14 and 15, this zone was seen in more than 90%. By the time invagination of the optic cup was complete, the ventral retinal zone of cell death had disappeared entirely in a large proportion of embryos; in all others, it shrank significantly both in volume and density of pyknotic fragments. In stage 19, when the first optic fiber fascicles begin to emerge from the retina, a dramatic increase occurs in the number of pyknotic fragments in the posterior pole of the retina. The appearance of dying cells, in a region shortly to be traversed by developing ganglion cell axons, supports the hypothesis that cell death processes are apparently somehow related to the creation of a suitable environment for the emergence of fibers toward the optic stalk. Densities of mitotic and interphasic cells as well as the mitotic index were determined in both the retinal zone of cell death and in areas devoid of dead cells. In all developmental stages analyzed, the mitotic index was notably lower in the former than in non-necrotic zones, suggesting that cell proliferation is partially inhibited in retinal areas of cell death.     

Expression of insulin-like growth factor II (IGF–II) in human hepatocellular carcinomas: An immunohistochemical study

Recent results obtained using molecular biology techniques have suggested a possible role for insulin-like growth factor II (IGF-II) in the pathogenesis of hepatocellular carcinoma (HCC). To investigate this phenomenon, a monoclonal anti-body was used against IGF-II to study 54 patients with HCC. The presence of HBsAg was also tested both in serum and liver tissue. A positive immunoreaction was found in 9/15 (60%) of the HCC arising in cirrhotic livers of patients who had serum markers for HBV (HBV+ positive patients). These results provide further evidence that HBV might play a role in the expression of IGF-II. In HCC of patients without any markers of HBV infection (HBV- negative patients), IGF–II was detected in 10/39 (25.6%) of the tumors, and in some benign neoplastic lesions. It was found not only in neoplastic cells but also in some dysplastic nodules. The speculation arises that IGF–II expression may play a role in some steps of hepato-carcinogenesis.     

Differential uptake of systemic fluorochrome Hoechst 33342 in lung and liver metastasis of B16 melanoma

Summary The growth and vascularization patterns of B16 melanoma colonies in the liver and lungs were measured and compared by histological techniques and dye diffusion patterns after injection of the fluorochrome Hoechst 33342. In the liver, the fluorescent pattern of dye diffusion revealed that uninodular tumours measuring up to 146 n in diameter were not functionally vascularized. However, when the nodules fused to give rise to multinodular tumours measuring between 256 and 366 n in diameter, a reticular dye diffusion pattern revealed functional tumour vascularization. In the lungs, subpleural, parenchymal and peritubular (i.e. surrounding blood vessels and airways) tumours were observed. The two former classes were vascularized down to thicknesses and diameters of 49 and 24 m respectively. In contrast, dye diffusion was never seen in peritubular tumour cuffs up to 609 m in thickness. The results indicate differences in vascularization patterns in B16 tumours in the liver and lungs, and differences between tumours growing in different sites within the lungs. If these results are applicable to metastases in these two organs, they indicate potential diffusion-mediated resistance to chemotherapy, and potential hypoxia-mediated resistance to radiotherapy of both metastases and micrometastases.