Low-dose oral or non-oral hormone therapy: effects on C-reactive protein and atrial natriuretic peptide in menopause.

OBJECTIVE: To assess the effects of oral low-dose and non-oral hormone therapy (HT) on ultra-sensitive C-reactive protein (CRP), atrial natriuretic peptide (ANP), and cardiovascular risk factors in postmenopause. METHODS: In this randomized, cross-over study, 44 recently postmenopausal women, with no clinical evidence of cardiovascular disease, received oral low-dose HT (estradiol 1 mg + drospirenone 2 mg/day) for 3 months. Forty-two patients received non-oral, conventional HT (1.5 mg/day percutaneous 17ß-estradiol gel or equivalent for nasal route) for 3 months followed by 200 mg/day micronized progesterone by the vaginal route (14 days during each menstrual period). After 3 months, patients were crossed over without washout. Post-HT vs. pre-HT measures were determined: lipids, glucose, body mass index, waist circumference, fibrinogen, CRP-stratified levels, and ANP levels. The study was registered at clinical trials.gov (NCT01432028). RESULTS: The mean age was 51 ± 3 years and the mean time since the menopause was 22 ± 10 months. CRP-stratified high levels decreased in a higher number of non-oral HT patients, who moved to intermediate and low levels (p = 0.02). No effect of HT was observed on ANP levels (baseline 67.4 (18.4-104.5), low-dose oral 43.5 (14.4-95.9), non-oral 39.8 (15.5-67.5) pg/ml). Markers of endothelial function did not worsen with either low-dose oral or non-oral HT: von Willebrand factor (baseline 118 ± 37%, low-dose oral 119 ± 38%, non-oral 108 ± 3%, p < 0.01), fibrinogen (baseline 356 ± 58 mg/dl; low-dose oral 343 ± 77 mg/dl; non-oral 326 ± 71 mg/dl, p < 0.01). CONCLUSIONS: Low-dose oral and non-oral HT for 6 months had neutral or beneficial effects in recently postmenopausal women with no clinical evidence of cardiovascular disease.

Rod precursors in the adult retina of the Austrolebias charrua annual fish.

Rod photoreceptors in the adult teleost retina are produced by rod precursors located in the outer nuclear layer (ONL). Annual fishes of the genus Austrolebias exhibit extensive adult retinal cell proliferation and neurogenesis, as well as surprising adaptive strategies to their extreme and changing environment, including adult retinal plasticity. Thus, here we identify and characterize rod precursors in the ONL of the Austrolebias charrua retina. For this aim we used classical histological techniques, transmission electron microscopy, detection of cell proliferation, and immunohistochemistry. Through these complementary approaches, we describe a cell population clearly distinguishable from photoreceptors in the ONL of the adult retina of A. charrua, which we propose corresponds to the rod precursor population. These cells exhibited particular morphological and ultrastructural characteristics, uptake of cell proliferation markers (BrdU+) and expression of stem cell markers (Sox2+). Determining the existence of the population of rod precursors is crucial to understand the sequence of events related to retinal plasticity and regeneration.

DNA sperm damage correlates with nuclear ultrastructural sperm defects in teratozoospermic men.

Sperm morphology has consistently been the best indicator of male fertility. Transmission electron microscopy currently provides the most information on the subcellular details of sperm structure. Recently, assessment of sperm DNA damage has been employed to assess fertility potential. The purpose of this work was to link sperm DNA damage, evaluated by an intercalated fluorescent dye, with the structural characteristics of sperm. Conventional semen analysis was performed on samples from men undergoing fertility evaluation. Thirty men were evaluated and assigned to three subgroups based on strict criteria for sperm morphology: normal morphology (>14% normal forms), intermediate morphology (5-14% normal forms), and poor morphology (<5% normal forms). By quantifying acridine orange-positive cells and ultrastructural sperm defects, we found that the poor morphology pattern group showed a positive association between sperm carrying damaged DNA and the percentage of sperm nucleus with vacuoles (P = 0.01). No statistically significant correlations were established in other ultrastructural characteristics of sperm, including immature chromatin, lytic changes, or abnormal sperm tails. These results suggest that zones without chromatin in the sperm nucleus reflect underlying chromosomal or DNA defects in severe teratozoospermic men. This association should be considered in the evaluation of male fertility.

Mitochondrial dysfunction in rat brain with aging Involvement of complex I, reactive oxygen species and cardiolipin.

Reactive oxygen species (ROS) are considered a key factor in brain aging process. Mitochondrial respiration is an important site of ROS production and hence a potential contributor to brain functional changes with aging. In this study we examined the effect of aging on complex I activity, oxygen consumption, ROS production and phospholipid composition in rat brain mitochondria. The activity of complex I was reduced by 30% in brain mitochondria from 24 months aged rats relative to young animals. These changes in complex I activity were associated with parallel changes in state 3 respiration. H(2)O(2) generation was significantly increased in mitochondria isolated from aged rats. The mitochondrial content of cardiolipin, a phospholipid required for optimal activity of complex I, decreased by 31% as function of aging, while there was a significant increase in the level of peroxidized cardiolipin. The age-related decrease in complex I activity in brain mitochondria could be reversed by exogenously added cardiolipin. This effect of cardiolipin could not be replaced by other phospholipids. It is proposed that aging causes brain mitochondrial complex I dysfunction which can be attributed to ROS-induced cardiolipin oxidation. These findings may prove useful in elucidating the mechanism underlying mitochondrial dysfunction associated with brain aging.

Protective effect of melatonin against mitochondrial dysfunction associated with cardiac ischemia- reperfusion: role of cardiolipin.

Reactive oxygen species (ROS) are considered an important factor in ischemia/reperfusion injury to cardiac myocytes. Mitochondrial respiration, mainly at the level of complex I and III, is an important source of ROS generation and hence a potential contributor of cardiac reperfusion injury. Appropriate antioxidant strategies could be particularly useful to limit this ROS generation and associated mitochondrial dysfunction. Melatonin has been shown to effectively protect against ischemic-reperfusion myocardial damage. The mechanism by which melatonin exerts this cardioprotective effect is not well established. In the present study we examined the effects of melatonin on various parameters of mitochondrial bioenergetics in a Langerdoff isolated perfused rat heart model. After isolation of mitochondria from control, ischemic-reperfused and melatonin-treated ischemic-reperfused rat heart, various bioenergetic parameters were evaluated such as rates of mitochondrial oxygen consumption, complex I and complex III activity, H2O2 production as well as the degree of lipid peroxidation, cardiolipin content, and cardiolipin oxidation. We found that reperfusion significantly altered all these mitochondrial parameters, while melatonin treatment had strong protective effect attenuating these alterations. This effect appears to be due, at least in part, to the preservation, by ROS attack, of the content and integrity of cardiolipin molecules which play a pivotal role in mitochondrial bioenergetics. Protection of mitochondrial dysfunction was associated with an improvement of post-ischemic hemodynamic function of the heart. Melatonin had also strong protective effect against oxidative alterations to complex I and III as well as to cardiolipin in isolated mitochondria.

Seminiferous epithelium cycle of a hantavirus reservoir, the long-tailed mouse Oligoryzomys flavescens (Rodentia-Cricetidae).

Oligoryzomys flavescens, a common rodent of the temperate regions of South America, has been identified as a Hantavirus reservoir. There is still little information concerning its reproductive biology, which is essential to devise effective control measurement of natural populations. This rodent is a seasonal breeder and adult males exhibit a short period of testicular regression during winter months (June-August). In the present study we provided a histological and ultrastructural analysis of the composition of the testis of sexually mature O. flavescens during the breeding season. Over 95% of the testicular parenchyma was occupied by the seminiferous tubules and less than 5% by the interstitial tissue. The mean tubular diameter and epithelium height were 147.2 and 57.8 microm, respectively. The spermatogenic wave was characterized and eight spermatogenesis stages were identified according to the tubular morphology method. Their length, estimated as their relative frequencies, were (I-VIII) 8.8, 14.9, 4.0, 5.0, 10.4, 5.8, 27.0, and 23.9. Ultrastructural features of spermiogenesis are shown for the first time in a sigmodontine rodent.

[Adenomatoid tumor of the epididymis]. / Tumor adenomatoide de epididimo.

OBJECTIVE: Paratesticular tumors are very rare and mostly bening. Wa aport a new case of adenomatoid tumor of epididymis METHOD: Male of 40 years old with solid lesion in epidididymis tale treated with mass exéresis RESULTS: Adenoamotid tumor of the epididymis confirmed with hystopathologic technique CONCLUSION: Adenomatoid tumor of epididymis is the most frequent paratesticular tumors and when is suspected, conservative surgery must be performed.

Shrinkage of freeze-dried cryosections of cells: Investigations by EFTEM and cryo-CLEM.

Freeze-drying of cryosections of cells or tissues is considered to be the most efficient preparation for microanalysis purpose related to transmission electron microscopy. It allows the measurements of ions and water contents at the ultrastructural level. However an important drawback is associated to freeze-drying: the shrinkage of the cryosections. The aim of this paper is the investigation of this phenomenon by means of three different methods applied to both hydrated and dehydrated cryosections: direct distance measurements on fiducial points, thickness measurements by energy filtered transmission microscopy (EFTEM) and cryo-correlative light electron microscopy (cryo-CLEM). Measurements in our experimental conditions reveal a lateral shrinkage around 10% but the most important result concerns the lack of differential shrinkage between most of the cellular compartments.

Differentiation of smooth muscle in the genital tract of the female mouse and its temporal relation with the development of the Wolffian nerve.

The development of the smooth muscle in the genital tract of the female mouse was studied by light and electron microscopy before and after birth. These studies showed that: a) between 13 days of fetal development and 2 days after birth the cells surrounding the Mullerian duct were undifferentiated and showed a fibroblast-like appearance; b) between 3 and 10 days after birth the cells acquired several characteristics of smooth muscle but they did not seem fully mature; c) between 30 and 180 days after birth the cells acquired a mature appearance; and d) the Wolffian nerve reached the Mullerian duct surrounding tissue before the start of smooth muscle differentiation.

Many-body interaction effects on the low-k structure of liquid Kr.

Neutron diffraction measurements and theoretical calculations of the structure factor S(k) of liquid Kr are extended to small k values (k<4 nm(-1)). The results show that many-body interaction contributions have an increasing effect on S(k) as k-->0, reaching at least 40% of the measured intensity. Both the phase diagram and the low-k structural data of dense Kr turn out to be closely reproduced by the hierarchical reference theory if additional many-body forces are taken into account by an augmented strength of the Axilrod-Teller triple-dipole potential. The experimental density derivative of S(k) is also used for a very sensitive test of the theories and interaction models considered here.

Physiological responses to child stimuli in mothers with and without a childhood history of physical abuse.

The present study investigated changes in heart rate, skin conductance, and self-reported affect in response to child stimuli in mothers with and without a childhood history of physical abuse. The stimuli were videotape presentations of a smiling and crying infant. During baseline periods (prior to videotape presentations), mothers without a childhood history of abuse displayed a significant reduction in skin conductance, which was not observed in mothers with a childhood history of abuse, suggesting that mothers without a history of abuse habituated to the experimental setting. Although the two groups of mothers did not differ in self-reported affect or in heart rates in response to the crying and smiling infant, mothers with a childhood history of abuse showed increases in skin conductance while viewing the smiling infant, but not while viewing the crying infant. In contrast, mothers without a childhood history of abuse showed increases in skin conductance during the presentation of the crying infant, but not while viewing the smiling infant. Similarities between the skin conductance results for mothers with and without a childhood history of abuse and skin conductance data reported for physically abusive and at-risk mothers are discussed.

Physiological responses to non-child-related stressors in mothers at risk for child abuse.

Physical child abusers and adults at risk for child abuse, relative to comparison subjects, are reported to be more physiologically reactive to child-related stressors. It is not known if the reported physiological reactivity is child specific or if physical child abusers and at-risk parents are also more reactive to other types of stressful stimuli. The present study investigated changes in heart rate and skin conductance in response to four types of non-child-related stressors in at-risk and matched low-risk mothers. The four types of stressful stimuli were: a cold pressor; a stressful film depicting industrial accidents; unsolvable anagrams; and an aversive car horn. At-risk mothers, relative to low-risk mothers, had greater and more prolonged sympathetic activation during presentations of the cold pressor and the stressful film, the stimuli rated as the most stressful. The present data, combined with previous findings, support the view that generalized sympathetic activation to both child and non-child-related stressors may serve as a mediator of physical child abuse.

[Arthropneumotomography in recurrent dislocations and subluxations of the shoulder. Methods, results, and indications in 45 cases (author's transl)]. / L'arthropneumotomographie dans les luxations récidivantes et les pseudoluxations de l'épaule. Technique, résultats et indications à propos de 45 cas.

The authors describe the results of arthropneumotomography in 45 patients with recurrent dislocations or subluxations of the shoulder. The method used is given in detail and the need for excellent quality glenoid profile sections, as described by Bernageau, is emphasized. The results are analyzed for bone lesions, capsuloligamentary lesions, and intra-articular foreign bodies. The two latter conditions are specifically demonstrated by arthropneumotomography. These results are then described radiological and surgical correlations, and the indications defined. Arthropneumotomography is therefore of value when a decision is to be taken as to the need for operation.

[New alternatives in the treatment of bacterial vaginosis]. / Nuevas alternativas en el tratamiento de la vaginosis bacteriana.

Efficiency and security clindamycin vaginal cream (2%) were compared to oral metronidazole's for the treatment of 184 women with symptomatic bacterial vaginosis in a multicentric, randomized, double-blind, controlled study. The treatment was of 7 days duration, using placebo capsules for the clindamycin group and placebo cream for the metronidazole group. Patients were observed during a follow up (4-13 and 20-43 days after completion of therapy). Global results of this treatment indicated that clindamycin vaginal cream offers a similar efficiency than oral metronidazole. Improvement or total healing was 87% for clindamycin and 79% for metronidazole, with no significant differences (p > 0.22). No relapses were observed in the clindamycin group, and 7% in the metronidazole group. The clindamycin group had a failure rate of 3% compared to 15% in the oral metronidazole group. Both drugs were well tolerated. Side effects more frequently reported were vulvovaginal irritation and cervicitis/vaginitis. The only side effect that could have been classified as serious was a generalized rash in a patient receiving metronidazole. It was concluded that clindamycin vaginal cream (2%) is an efficient and secure alternative to oral metronidazole for the treatment of bacterial vaginosis being the elective therapy for pregnant women in their first gestational trimester.

[Microbial etiology of mild and moderate pelvic inflammatory disease]. / Etiología microbiana de la enfermedad inflamatoria pélvica leve y moderada (EIP).

Pelvic inflammatory disease (PID) is one of the most severe complications of sexually transmitted disease (STD). It can be due to the ascending of normal endogenous microorganisms of the female genital tract or the infection by microorganisms related to STD as Chlamydia trachomatis and Neisseria gonorrhoeae. PID leads to serious gynecoobstetric consequences as infertility and ectopic pregnancy. Clinicians face the problem of knowing the ethiology of PID in order to treat appropriatly patients with this clinical diagnosis. So that, this work pretends to establish what kind of microorganisms are implicated in PID. A proper isolation and identification of microorganisms achieved by culture of lower genital tract samples from endocervix, endometrium and peritoneal fluid, leading to a betther, specific and proper treatment of this disease.

[Bladder substitution using the double-folded ileum technic (Goodwin's cup-patch technic)]. / Vessie de substitution faite au moyen de l'iléon replié (Goodwin's cup-patch technique).

An internal urinary diversion after radical cystoprostatectomy has been performed in 70 male patients. The bladder substitute was made from an ileal segment, opened along its antimesenteric border and folded twice, according to Goodwin's "cup-patch technique". After an observation time of 6 months to 6 years, the results are in general good: The initial capacity of the pouch made from only 40 cm of ileum (in order to avoid metabolic disturbances) increases to a functional capacity of 500 ml within the first postoperative weeks. The increase of the bladder substitute's capacity is parallel to the improvement of urinary continence. In general, the latter is achieved after 1-3 months during the day, and after 3-6 months during the night. However, loss of a few drops of urine may occur, reason why half of our patients wear a safety pad later than 6 months after surgery, at least during the night. There was no significant difference between those patients with an antireflux nipple and those patients having an ileal tubular afferent segment.

Olfacto-retinalis pathway in Austrolebias charrua fishes: a neuronal tracer study.

The olfacto-retinal centrifugal system, a constant component of the central nervous system that appears to exist in all vertebrate groups, is part of the terminal nerve (TN) complex. TN allows the integration of different sensory modalities, and its anatomic variability may have functional and evolutionary significance. We propose that the olfacto-retinal branch of TN is an important anatomical link that allows the functional interaction between olfactory and visual systems in Austrolebias. By injecting three different neuronal tracers (biocytin, horseradish peroxidase, and 1,1'-dioctadecyl-3,3,3',3'tetramethyl-indocarbocyanine perchlorate (DiI)) in the left eye of Austrolebias charrua fishes, we identified the olfacto-retinal branch of TN and related neuronal somas that were differentiable by location, shape, and size. The olfacto-retinal TN branch is composed of numerous thin axons that run ventrally along the olfactory bulb (OB) and telencephalic lobes, and appears to originate from a group of many small monopolar neurons located in the rostral portion of both the ipsi- and contralateral OB (referred to as region 1). Labeled cells were found in two other regions: bipolar and multipolar neurons in the transition between the OB and telencephalic lobes (region 2) and two other groups in the preoptic/pretectal area (region 3). In this last region, the most rostral group is constituted by monopolar pear-shaped neurons and may belong to the septo-preoptic TN complex. The second group, putatively located in the pretectal region, is formed by pseudounipolar neurons and coincides with a conserved vertebrate nucleus of the centrifugal retinal system not involved in the TN complex. The found that connections between the olfactory and visual systems via the olfacto-retinal TN branch suggest an early interaction between these sensory modalities, and contribute to the identification of their currently unknown circuital organization.

Proliferation zones in the brain of adult fish Austrolebias (Cyprinodontiform: Rivulidae): a comparative study.

In contrast with mammals, adult fish brains exhibit an enormous potential to produce new cells. Proliferation zones, however, have been described in only a few species, hindering comparisons among genuses and orders. Here we analyzed brain cell proliferation in annual teleostean fishes Austrolebias (Cyprinodontiform: Rivulidae). Immunocytochemistry against 5-bromo-2'-deoxyuridine (BrdU) was quantitated and mapped 24 h after injection in three species with different phylogenetic positions or habitats. All species had similar brain anatomy and total volume, but olfactory bulbs, torus longitudinalis and cerebellum were of different sizes in different species. Cell proliferation was found throughout the brain. Three-D reconstructions provided evidence for contiguity along the rostro-caudal axis and concentration in the vicinity of the ventricles. Brain regions analyzed exhibited high mitotic activity, and the torus longitudinalis had the highest volume-normalized proliferation index. A. affinis exhibited the highest normalized proliferation indexes in visual regions but the lowest in olfactory bulb. A. reicherti showed an inverse pattern, suggesting that these species have a different hierarchy of sensorial modalities that could be related to phylogeny or habitat. Double immunostaining against BrdU and cell-type specific markers was performed to determine the fate of proliferating cells. A widespread gliogenesis was evidenced. Few cells positive for both BrdU and the neuronal marker HuC/D were found in the brain of the three species, demonstrating neurogenesis in the adult Austrolebias brain. Summarizing, adult members of the three species showed similar brain anatomy and cell proliferation patterns. Among species, volume-normalized proliferation indexes varied in regions involved in different sensory modalities. To our knowledge, this is the first report showing proliferating cells with neuronal markers as earlier as 24 h after BrdU injection.

Influence of habitual physical activity on body composition, fat distribution and metabolic variables in early postmenopausal women receiving hormonal therapy.

OBJECTIVE: To determine whether there is an association between the level of habitual physical activity, body composition and anthropometric and metabolic variables in postmenopausal patients before and after hormone replacement therapy (HRT). STUDY DESIGN: Thirty-four healthy, recent postmenopausal women (50+/-2.7 years; 23.8+/-10 months since menopause) consulting for symptoms of estrogen deficiency were included in the study. Anthropometric assessment, percent of body fat (BF) estimated by skinfold measures, and metabolic evaluation were performed before and 4 months after the start of HRT, which included non-oral or low-dose oral preparations. The status of physical activity was defined by counting steps with a pedometer. Patients were stratified as active (6000 steps ore more per day) or inactive (fewer than 6000 steps per day). Results are expressed as mean+/-SD or median and interquartile range. log 10 transformation was used to normalize the distribution of non-Gaussian variables. ANOVA for repeated measures was performed for the active and inactive groups, before and after HT. Pearson correlation coefficient was used to investigate the relationship between anthropometric and metabolic variables and habitual physical activity. RESULTS: BMI and BF did not change with HRT in comparison with baseline. In contrast, a decline was observed in waist circumference (WC) and waist to hip ratio (WHR) after HRT in both active and inactive women (P<0.01). While triglycerides and glucose did not change after HRT, total and LDL-cholesterol decreased from baseline. In contrast, after HRT, active patients were found to have lower BF than inactive women (active: 25.4+/-2.5; inactive: 26.6+/-2, P=0.01). There was a significant negative correlation between habitual physical activity (number of steps per day) and BF (r=-0.36, P=0.04). After HRT, when only active patients were considered, a significant negative correlation was found between the number of steps and WC (r=-0.42, P=0.04) and WHR (r= -0.58, P=0.03). CONCLUSION: Habitual physical activity plays a major role in preserving a favorable cardiovascular profile in postmenopausal patients using HRT.