Impact of postmenopausal vaginal discomfort on sex and relationships in Brazil: the CLOSER survey.

OBJECTIVE: The CLOSER (CLarifying Vaginal Atrophy's Impact On SEx and Relationships) survey investigated how postmenopausal vaginal atrophy (VA) affects relationships between Brazilian women and male partners. METHODS: Postmenopausal women (age 55-65 years) with VA, and male partners of women with the condition, completed an online survey on the impact of VA and local estrogen treatment on intimacy and relationships. RESULTS: A total of 360 women and 352 men from Brazil were included. Women (83%) and men (91%) reported that they were comfortable discussing VA with their partners. Women's key source of information on VA was health-care providers (HCPs), but 44% felt that not enough information is available. VA caused 70% of women to avoid sexual intimacy and resulted in less satisfying sex. VA had a negative impact on women's feelings and self-esteem. Women (76%) and men (70%) both reported that treatment with vaginal estrogen improved their sexual relationship, primarily by alleviating women's pain during sex. Women (56%) and men (59%) felt closer to each other after treatment. CONCLUSIONS: VA had a negative impact on sexual relationships for both women and men in Brazil, and reduced women's self-confidence. Vaginal hormone therapy improved couples' sexual relationships. A proactive attitude of HCPs is essential to educate women on VA and the potential benefits of treatment.

Vaginal Health: Insights, Views & Attitudes survey in Latin America (VIVA-LATAM): focus on Brazil.

OBJECTIVE: A previous survey investigated postmenopausal vaginal atrophy in a sample of women across Latin America. To help implement a tailored approach to improve postmenopausal care and outcomes in Brazil, we consider results from the survey for this country. METHODS: A total of 2509 postmenopausal women resident in Argentina, Brazil, Chile, Colombia, or Mexico completed an online questionnaire. The Brazilian cohort comprised 504 women. RESULTS: Over half of the Brazilian cohort (56%) reported experiencing symptoms of vaginal atrophy; most described them as moderate or severe (76%), and almost half (48%) experienced symptoms for at least 1 year. Three-quarters of the Brazilian cohort (75%) were unaware of the chronic nature of the condition. Upon experiencing symptoms of vaginal atrophy, 92% had visited a health-care provider to discuss treatment options. Overall, 56% were aware of some form of local hormone therapy and 40% of those affected by vaginal atrophy had used such treatment. CONCLUSION: Postmenopausal women in Brazil are likely to benefit from increased awareness of the symptoms of vaginal atrophy. Health-care providers can potentially improve outcomes by helping women to understand the chronic nature of the condition and available treatment options. Women may be open to education pre menopause, before symptoms occur.

Androgens and bone.

Testosterone is the major gonadal sex steroid produced by the testes in men. Androgens induce male sexual differentiation before birth and sexual maturation during puberty; in adult men, they maintain the function of the male genital system, including spermatogenesis. Testosterone is also produced in smaller amounts by the ovaries in women. The adrenal glands produce the weaker androgens dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione. Because testosterone can be metabolized to estradiol by the aromatase enzyme, there has been controversy as to which gonadal sex steroid has the greater skeletal effect. In this respect, there is increasing evidence that at least part of the effects of androgens in men can be explained by their aromatization into estrogens. The current evidence suggests that estradiol plays a greater role in maintenance of skeletal health than testosterone, but that androgens also have direct beneficial effects on bone.

Osteoporosis after solid organ transplantation.

Osteoporosis and high risk of fractures have emerged as frequent and devastating complications of organ solid transplantation process. Bone loss after organ transplant is related to adverse effects of immunosuppressive drugs on bone remodeling and bone quality. Many factors contribute to the pathogenesis of osteoporosis in transplanted patients. This review address the mechanisms of bone loss that occurs both in the early and late post-transplant periods including the contribution of the immunosuppressive agents as well as the specific features to bone loss after kidney, lung, liver and cardiac transplantation. Therapy for bone loss and prevention of fragility fracture in the transplant recipient will also be discussed.

Differential nicotinic receptor expression in monkey basal ganglia: effects of nigrostriatal damage.

Our previous work showed that there were marked declines in (125)I-alpha-conotoxin MII labeled nicotinic receptors in monkey basal ganglia after nigrostriatal damage, findings that suggest alpha3/alpha6 containing nicotinic receptors sites may be of relevance to Parkinson's disease. We now investigate whether there are differential changes in the distribution pattern of nicotinic receptor subtypes in the basal ganglia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned animals compared to controls to better understand the changes occurring with nigrostriatal damage. To approach this we used (125)I-alpha-conotoxin MII, a marker for alpha3/alpha6 nicotinic receptors, and (125)I-epibatidine, a ligand that labels multiple nicotinic subtypes. The results demonstrate that there were medial to lateral gradients in nicotinic receptor distribution in control striatum, as well as ventromedial to dorsolateral gradients in the substantia nigra, which resembled those of the dopamine transporter in these same brain regions. Treatment with MPTP, a neurotoxin that selectively destroys dopaminergic nigrostriatal neurons, led to a relatively uniform decrease in nicotinic receptor sites in the striatum, but a differential effect in the substantia nigra with significantly greater declines in the ventrolateral portion. Competition analysis in the striatum showed that alpha-conotoxin MII sensitive sites were primarily affected after lesioning, whereas multiple nicotinic receptor populations were decreased in the substantia nigra. From these data we suggest that in the striatum alpha3/alpha6 nicotinic receptors are primarily localized on dopaminergic nerve terminals, while multiple nicotinic receptor subtypes are present on dopaminergic cell bodies in the substantia nigra. Thus, if activation of striatal nicotinic receptors is key in the regulation of basal ganglia function, alpha3/alpha6-directed nicotinic receptor ligands may be more relevant for Parkinson's disease therapy. However, nicotinic receptor ligands with a broader specificity may be more important if receptors in the substantia nigra play a dominant role in controlling nigrostriatal activity.

Vulnerability of 125I-alpha-conotoxin MII binding sites to nigrostriatal damage in monkey.

Parkinson's disease, a neurodegenerative movement disorder characterized by selective degeneration of nigrostriatal dopaminergic neurons, affects approximately 1% of the population over 50. Because nicotinic acetylcholine receptors (nAChRs) may represent an important therapeutic target for this disorder, we performed experiments to elucidate the subtypes altered with nigrostriatal damage in parkinsonian monkeys. For this purpose we used (125)I-alpha-conotoxin MII (CtxMII), a relatively new ligand that identifies alpha3 and/or alpha6 subunits containing nAChR subtypes. In brain from untreated monkeys, there was saturable (125)I-alpha-CtxMII binding to a single population of high-affinity nicotinic sites (K(d) = 0.9 nm), primarily localized in the visual, habenula-interpeduncular, and nigrostriatal-mesolimbic pathways. Administration of the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine resulted in damage to the nigrostriatal system and parkinsonism. Autoradiographic analysis showed that (125)I-alpha-CtxMII sites were selectively reduced (>/=99%) in the basal ganglia and that the lesion-induced decreases correlated well with declines in the dopamine transporter, a marker of dopaminergic neuron integrity. These findings may indicate that most or all of (125)I-alpha-CtxMII-labeled nAChR subtypes in the basal ganglia are present on nigrostriatal dopaminergic neurons, in contrast to (125)I-epibatidine sites. These data suggest that the development of ligands directed to nAChR subtypes containing alpha3 and/or alpha6 subunits may yield a novel treatment strategy for parkinsonian patients with nigrostriatal dopaminergic degeneration.

Nicotine-evoked transmitter release from synaptosomes: functional association of specific presynaptic acetylcholine receptors and voltage-gated calcium channels.

It has previously been shown that nicotine-evoked dopamine release from rat striatal synaptosomes and nicotine-evoked norepinephrine release from hippocampal synaptosomes are mediated by distinct nicotinic acetylcholine receptor (nAChR) subtypes. In the present study, the functional association of these nicotinic receptors with specific subtypes of voltage-gated calcium channels was examined. Cd(2+) (200 microM), as well as omega-conotoxin MVIIC (5 microM), blocks approximately 85% of nicotine-evoked dopamine release from striatal synaptosomes, indicating a major involvement of calcium channels. Furthermore, the toxin-susceptibility suggests that these calcium channels contain alpha(1A) and/or alpha(1B) subunits. Inhibition of nicotine-evoked dopamine release by conotoxins alpha-MII and omega-GVIA is additive and indicates that presynaptic alpha3beta2 nAChRs are functionally coupled to alpha(1A), but not alpha(1B), calcium channel subtypes. Conversely, insensitivity to alpha-AuIB and sensitivity to omega-MVIIC indicate that non-alpha3beta2/alpha3beta4-containing nAChRs are functionally coupled to alpha(1B)-containing calcium channels. In contrast, Cd(2+) blocks only 65% of nicotine-evoked norepinephrine release from hippocampal synaptosomes, indicating that a substantial fraction of this release occurs through mechanisms not involving calcium channels. This Cd(2+)-insensitive component of release is blocked by alpha-AuIB and therefore appears to be triggered by Ca(2+) flowing directly through the channels of presynaptic alpha3beta4 nAChRs. Thus, these data indicate that different presynaptic termini can have distinctive functional associations of specific nAChRs and voltage-gated calcium channels.

alpha-conotoxin AuIB selectively blocks alpha3 beta4 nicotinic acetylcholine receptors and nicotine-evoked norepinephrine release.

Neuronal nicotinic acetylcholine receptors (nAChRs) with putative alpha3 beta4-subunits have been implicated in the mediation of signaling in various systems, including ganglionic transmission peripherally and nicotine-evoked neurotransmitter release centrally. However, progress in the characterization of these receptors has been hampered by a lack of alpha3 beta4-selective ligands. In this report, we describe the purification and characterization of an alpha3 beta4 nAChR antagonist, alpha-conotoxin AuIB, from the venom of the "court cone," Conus aulicus. We also describe the total chemical synthesis of this and two related peptides that were also isolated from the venom. alpha-Conotoxin AuIB blocks alpha3 beta4 nAChRs expressed in Xenopus oocytes with an IC50 of 0.75 microM, a kon of 1.4 x 10(6) min-1 M-1, a koff of 0.48 min-1, and a Kd of 0.5 microM. Furthermore, alpha-conotoxin AuIB blocks the alpha3 beta4 receptor with >100-fold higher potency than other receptor subunit combinations, including alpha2 beta2, alpha2 beta4, alpha3 beta2, alpha4 beta2, alpha4 beta4, and alpha1 beta1 gamma delta. Thus, AuIB is a novel, selective probe for alpha3 beta4 nAChRs. AuIB (1-5 microM) blocks 20-35% of the nicotine-stimulated norepinephrine release from rat hippocampal synaptosomes, whereas nicotine-evoked dopamine release from striatal synaptosomes is not affected. Conversely, the alpha3 beta2-specific alpha-conotoxin MII (100 nM) blocks 33% of striatal dopamine release but not hippocampal norepinephrine release. This suggests that in the respective systems, alpha3 beta4-containing nAChRs mediate norepinephrine release, whereas alpha3 beta2-containing receptors mediate dopamine release.

Alpha-conotoxin MII blocks nicotine-stimulated dopamine release in rat striatal synaptosomes.

Activation of presynaptic nicotinic acetylcholine receptors (nAChRs) can induce the release of neurotransmitters such as dopamine and norepinephrine in the CNS. Accumulating evidence suggests that distinct nAChR subtypes are involved; however, it has been difficult to determine the subunit composition of these receptors, in part because of the lack of a sufficient variety of selective nAChR ligands. We present experimental data that at least two different nAChR complexes are involved in dopamine release, one of which has an alpha3/beta2 subunit interface. The recently discovered peptide alpha-conotoxin MII is a potent and selective inhibitor of rat nAChRs containing an interface formed by alpha3 and beta2 subunits. We used this peptide to examine nicotine-stimulated release of dopamine from rat striatal synaptosomes and of norepinephrine from hippocampal synaptosomes. MII (100 nM) blocks 34-49% of the nicotine-stimulated dopamine release, but not dopamine release evoked by elevated [K+]. Furthermore, two peptides structurally related to alpha-conotoxin MII, namely alpha-conotoxin MI (selective for alpha1beta1gammadelta nAChRs) and alpha-conotoxin ImI (selective for alpha7-containing nAChRs), have no effect on nicotine-stimulated dopamine release. The results indicate that one third to half of the dopamine release in the striatal preparation is mediated by nAChRs with an alpha3/beta2 subunit interface. In contrast,

[Effects of prophylactic doses of potassium iodide on the course of thyroid diseases (1986-1990) diagnosed due to the atomic accident at Czernobyl in adult patients at the outpatient endocrinologic hospital clinic in Lodz]. / Wplyw profilaktycznej dawki jodku potasu na przebieg chorób tarczycy (1986-1990) zdiagnozowanych przed awaria elektrowni atomowej w Czarnobylu u doroslych pacjentów Poradni Endokrynologicznej Szpitala Klinicznego nr 3 Akademii Medycznej w Lodzi.

2521 patients of the Lódz Outpatient Endocrinological Clinic (2290 females, 231 males; inhabitants of the central region of Poland Lódz City, Lódz Metropolitan Area, Piotrków, Plock, Sieradz, Skierniewice and Wloclawek Provinces in which committed dose equivalent to the thyroid was between 2.7-7.0 mSv [min.-max.] in Skierniewice Province and 4.6-11.7 mSv in Plock Province) were included in the study. The patients were divided into 5 groups: I--persons who did not take the protective dose of potassium iodide (KI) after Chernobyl Nuclear Power Plant accident and did not received any treatment with thyroid preparations or hormones at that time (n = 1282), II--patients who receive KI, once or several times (n = 774), III--patients who took orally iodine tincture or other iodine-containing preparations for the above purposes (n-37), IV--patients who took tablets of Thyroideum (Polfa) Thyroideum siccum (dry thyroid extract), once or several times, as a prophylactic action (n = 79), V--patients who were in the course of continuous treatment with Thyreoideum or thyroid hormones at the time of Chernobyl accident (n = 349). The analysis was performed for all the patients jointly, as well as separately for: either sex, three age groups (18-30, 31-55, 56-70 yrs) and 7 administrative areas specified above. All the patients were subjected into complex clinical examination, serum TSH, T3, T4 concentrations, anti-thyroid membrane antibodies (ATMA) and antithyroglobulin antibodies (ATg) titres, as well as ultrasound, scintigraphy, and fine needle aspiration biopsy of the thyroid (the last two according to indications) included. The patients were also examined by means of a special questionnaire (Patient's Inquiry Sheet), which was subsequently submitted to computer analysis. All the doctors' diagnoses from 1986 (17 different diagnoses) and 1990 (27 different diagnoses), as well as the course of diseases, were verified with use of a specially prepared IBM PC/AT computer program ChernStat.(ABSTRACT TRUNCATED AT 400 WORDS)