37-39 Full-length huntingtin protein as well as truncated versions of the protein with a polyglutamine sequence in the pathological range (40-150 glutamines) were expressed in mice under the control of different promoters. The majority of these studies suggest that the formation of Nils is correlated with the appearance of progressive neuronal dysfunction and toxicity. Thus, it is reasonable to assume that reduction of inclusion body formation and huntingtin aggregation

may have a beneficial effect on disease progression Inhibitors,research,lifescience,medical in HD patients. Using a conditional mouse model of HD, Yamamoto et al40 demonstrated that blocking the expression of mutant huntingtin protein in neurons resulted in the disappearance of inclusions and the behavioral phenotype. Therefore, reduction of HD protein expression in patients and/or stimulation of natural clearance mechanisms could be effective therapeutic

strategies for HD. Apart from Nils, inclusion bodies with aggregated huntingtin protein were recently detected in Inhibitors,research,lifescience,medical axons and axon terminals of striatal neurons.41 These structures were termed neuropil aggregates. The formation of these aggregates is likely to affect specific neuronal functions such as axonal transport and neurotransmitter release or uptake in axon terminals. Therefore, the deposition of mutant huntingtin protein in the terminals of striatal neurons, Inhibitors,research,lifescience,medical which are affected most in HD, may contribute to the selective neuropathology Inhibitors,research,lifescience,medical of HD. After the discovery of Nils in brains of transgenic animals,35 similar structures were detected in postmortem brains of HD patients.6, 7 Nils were found in neurons but not

in glia cells. Immunohistochemical studies showed that they are most abundant Inhibitors,research,lifescience,medical in the striatum and the cerebral cortex, the areas most affected by HD. In the striatum, inclusions were found in the medium spiny neurons that are selectively lost during HD. Nils in patient brains are detected by antibodies directed against the N-terminus of huntingtin, but not by antibodies that recognize the C-terminus of the protein, indicating that a truncated N-terminal huntingtin fragment rather than the full-length protein is present in the Nils of patients. Like the Nils in transgenic animals, the Nils in patients were stained with anti-ubiquitin antibodies. These results suggest that the truncated huntingtin protein present in the inclusion bodies is ubiquitinated others but cannot be degraded by the proteasome system.42 Ultrastructural studies revealed that Nils in patient brains contain aggregated huntingtin protein with a fibrillar and granular selleck morphology. In addition, dystrophic neurites containing aggregated huntingtin protein were detected.6 Dystrophic neurites are known to result from dysfunction of neuronal retrograde transport. Formation of insoluble huntingtin aggregates could alter this process in neuronal cells.

The Maimonides portrait is undoubtedly one of the world’s most famous and easily recognizable universal icons. Portraits, including those of Jewish prominent leaders and scholars, became fashionable long after Maimonides died. We have no way of knowing what Maimonides really looked like, yet a single utterly imaginative “portrait” has successfully Inhibitors,research,lifescience,medical defined our conception of Maimonides for ever. Of the numerous available versions of this portrait let us focus on the pen-and-ink drawing frequently cited and known as “portrait and autograph” (Figure 1).1 The depicted Maimonides signature in this picture is unequivocally authentic and resembles his numerous verified signatures

found in the Cairo Genizah (Figure 2).2 However, many intriguing questions come to mind when appraising the portrait itself. In the following article we’ll try to answer these questions. Figure 1 Maimonides’ traditional portrait and autograph.1 This nineteenth-century imaginative depiction,

Inhibitors,research,lifescience,medical courtesy of the Granger Collection, NY, is possibly by the American illustrator Arthur Burdett Frost. Figure 2 The enlarged signature in the picture (above) compared to Inhibitors,research,lifescience,medical the almost identical authentic one found in the Cairo Genizah (below).2 HOW AND WHEN DID THIS PARTICULAR PORTRAIT BECOME ASSOCIATED WITH MAIMONIDES? The earliest Maimonides portrait, dating back to the fifteenth century, Inhibitors,research,lifescience,medical is attributed to Professor Moshe-David (Umberto) Cassuto (1883–1951) who reportedly 3 discovered it in 1935. Professor Umberto Cassuto, a member of the Academic Council of the Hebrew University in Jerusalem, has discovered a new portrait of Maimonides made in the 15th century. The portrait is coloured and is of rare artistic value, showing Maimonides in oriental dress. Regretfully, the exact details of that particular intriguing discovery are unknown. Professor Cassuto, a renowned Rabbi and scholar, has written the Maimonides article in the Treccani Encyclopedia and was intimately familiar with the rare handwritten and beautifully illuminated copies Inhibitors,research,lifescience,medical Phosphoprotein phosphatase of the Mishneh

Torah created in Italy and Spain in the fifteenth century. It is plausible that, while cataloguing all Hebrew find more manuscripts in the Vatican Library (later to be published as Codices Vaticani Hebraici), Professor Cassuto has indeed encountered and identified such a portrait. Luckily much more is known about a portrait that dates back to the eighteenth century. This image was probably first “discovered” in the mid-nineteenth century by Yashar (R. Isacco Samuele Reggio, 1784–1855), an Austro-Italian scholar, mathematician, voluminous writer, and rabbi born at Gorizia. Reggio was one of the prominent leaders of Jewish emancipation and found the portrait in a 34-volume encyclopedic work called Thesaurus Antiquitatum Sacrarum (1744–1769).

Pre-existing neuropathies are not a contraindication to treatment. Central neurotoxicity may occur and may be severe especially with paclitaxel. Myalgia and/or arthralgia typically appear 2-3 days after drug administration, resolve within a few days, and are unrelated to dose (41),(42). Docetaxel-associated neuropathy occurs less frequently and with less severity than paclitaxel-associated neuropathy (42). Reversible fluid retention syndrome (42),(43), which is characterized by edema and third-space fluid retention, is a unique side effect of docetaxel. Bowel wall edema and pleural and peritoneal fluid retention are common manifestations of this syndrome, Inhibitors,research,lifescience,medical which

is caused by a docetaxel-induced increase in capillary permeability. The most Inhibitors,research,lifescience,medical serve end-organ complication of third-space fluid collection is heart failure. This severe complication can be ameliorated and prevented with prophylactic administration of corticosteroids, along with aggressive and early administration of diuretics (43). No less important, but less frequently reported, toxicities associated with taxanes include fatigue, mucositis,

Inhibitors,research,lifescience,medical gastrointestinal symptoms, phlebitis, drug-induced adult respiratory distress syndrome (for docetaxel), and bradycardia plus swollen, red, painful mouth (for paclitaxel). Fatigue is BIX 01294 research buy observed in 58-67% of the patients treated with docetaxel, and it is occasionally severe enough to cause a modification in dose (33). Mucositis typically results from slow infusion, and it occurs more frequently in patients treated with docetaxel than with paclitaxel. Although less-severe gastrointestinal toxicityties, such as nausea, vomiting, and diarrhea, also occur more frequently Inhibitors,research,lifescience,medical with docetaxel, grade 3/4 gastrointestinal toxicities are uncommon (42). Table 1 summarizes the rare adverse effects associated taxanes. Table 1 Rare side effects associated

with taxanes Clinical use of taxanes in the treatment/management of advanced gastroesophageal cancers For many solid Inhibitors,research,lifescience,medical tumors, tumor responses and survival outcomes are higher with CRT than with radiotherapy (RT) alone (44)-(49). For patients with solid tumors, CRT is used to palliate symptoms, treat definitively, and contribute significantly to multimodality therapy. Chemotherapeutic agents have been and successfully used as radiosentisizers; platinums, fluoropyrimidines, and taxanes are the most commonly used chemotherapeutic agents. The results of the Radiation Therapy Oncology Group (RTOG) 85-01 trial (49) established that local disease control and survival outcome were both improved with CRT (RT combined with cisplatin and 5-FU) compared with RT alone. Therefore, most large randomized studies of CRT in GECs have been designed with either 5-FU, cisplatin, or both as radiosensitizers. Although taxanes are used as part of CRT for GECs, their use as radiosensitizers has been limited to phase II single-arm studies of patients with both resectable and locally advanced (unresectable) disease (50).

g., Alzheimer’s disease, vascular dementia; Pakrasi and O’Brien 2005; Austin et al. 2011) and has also been linked with more subtle deficits in nearly all domains of cognitive function in persons with cardiovascular disease (CVD; Jefferson et al. 2007a,b; HDAC inhibitor Appleman et al. 2010; Moser et al. 2012). The inverse association between CBF and cognitive function likely stems from the adverse effects of cerebral hypoperfusion on the brain (Jefferson

et al. 2007a; Jerskey et al. 2009). Reduced CBF has been shown to predict decreased Inhibitors,research,lifescience,medical brain volume in persons with diabetes (van Elderen et al. 2011). Measures of systemic perfusion (e.g., cardiac indices) also significantly correlate with abnormal brain aging (e.g., smaller brain volume, white matter hyperintensities [WMH]) in patients with cardiac disease (Jefferson et al. 2007b, 2010; Jefferson 2010). Extant evidence also shows that reduced CBF is associated with structural and functional brain abnormalities in a wide range of medical and neurological populations (e.g., Alzheimer’s disease, stroke patients; Inhibitors,research,lifescience,medical Austin et al. 2011; Aoi et al. 2012). Despite these findings, the independent effects of cerebral perfusion on cognitive function and brain structure remains poorly understood. Inhibitors,research,lifescience,medical Recent studies have used positron emission tomography (PET) and found global CBF was inversely associated with cognitive test performance among vascular disease patients; however, findings from these

studies are limited by small sample sizes and lack of control for confounding comorbid medical conditions that influence neurocognitive outcomes (Kitagawa et al. 2009; Brundel Inhibitors,research,lifescience,medical et

al. 2012; Moser et al. 2012). Even further, limited research has used arterial spin labeling (ASL) to examine the relationship between CBF and neurocognitive outcomes in aging older adults with CVD. This is unfortunate, as rapidly growing attention has been paid to the use of ASL imaging in detecting individuals at risk for neurodegenerative disorders (e.g., Alzheimer’s disease), including conversion from normal aging to dementia (Chao et al. 2010; Alexopoulos et al. 2012; Inhibitors,research,lifescience,medical Bangen et al. 2012; Wolk and Detre 2012). Past work also shows ASL imaging is sensitive to brain perfusion abnormalities in stroke oxyclozanide survivors even before the onset of structural brain injury – though this study was limited to sample size of three participants (Brumm et al. 2010). In light of these findings, ASL imaging may also serve as a useful biomarker for poor neurocognitive outcomes in aging older adults with CVD at risk for cognitive impairment, though no study has examined this possibility. The purpose of the current study was to examine the independent associations among cerebral perfusion using ASL imaging, structural brain indices (e.g., volume and cortical thickness), and cognitive test performance among a larger sample of older adults with varying degrees of vascular disease.

Fixed drug eruptions are also relatively common adverse cutaneous reactions with several atypical and some typical antipsychotics as well as with other psychotropics [Bhattacharjee and El-Sayeh, 2008]. The onset is usually within a few days of ingestion, affects any part of the body, and may involve the mucosal membranes [Valeyrie-Allanore et al. 2007]. Severe cutaneous eruptions, such as erythema multiforme, have been reported Inhibitors,research,lifescience,medical much less frequently with several atypical and some typical antipsychotics [Warnock and Morris, 2002a]. The onset is slower, typically 1–3 weeks after initiation

[Svensson et al. 2000], but this may potentially develop into a more serious reaction such as Stevens–Johnson syndrome (SJS)

or toxic epidermal necrolysis [Warnock and Morris, 2002a]. When a severe cutaneous reaction develops the suspected causal agent should be immediately withdrawn [Kimyai-Asadi et al. 1999; Svensson et al. 2000; Warnock and Morris, 2002a]. Here the author presents a case of a severe and potentially Inhibitors,research,lifescience,medical life-threatening adverse cutaneous reaction following initiation of oral aripiprazole. Case presentation A 61-year-old Moroccan gentleman with a long-standing diagnosis of schizophrenia had been this website treated with flupentixol decanoate depot since 1976. Over the years this had been prescribed at varying doses and at times with the addition of other antipsychotics, such as trifluoperazine. Inhibitors,research,lifescience,medical Throughout this time he regularly suffered with extrapyramidal side-effects (EPSs) for which he took oral procyclidine. He had residual but manageable psychotic symptoms and no psychiatric admissions. He was obese, had type 2 diabetes for which he took

metformin and had no Inhibitors,research,lifescience,medical known drug allergies. He was prescribed flupentixol decanoate 150 mg fortnightly. At lower doses the psychotic symptoms became more problematic although the EPS lessened; at this dose the ongoing EPS included pill rolling tremor in his left hand, poverty of facial expression, festinating Inhibitors,research,lifescience,medical gait and oculogyric crises. The latter were described and verified by both him and his wife, although not observed during clinic appointments; they appeared independently of time, location and setting, and happened several times a week. Both he and his wife found these very distressing. He was already taking Astemizole procyclidine 5 mg usually twice a day but often more, and carried these tablets with him in his pocket. An additional 5–10 mg of procyclidine was effective at treating an oculogyric crisis. A suggestion was made to try an alternative antipsychotic. He had only previously taken typical antipsychotics, and in view of his physical health, comorbidities and concurrent medication, a limited range of atypicals were considered. Following discussions between the pharmacist, the patient and his wife, a mutual decision was made to change to aripiprazole.

Memantine Memantine is a nonselective NMDA receptor

antagonist that is reported to have antidepressant actions in rodent models64,67; there are no data on the effects of memantine on mTORC1 signaling or synapse formation. Memantine is approved for use in humans (ie, Alzheimer’s disease) for which it has modest effects.68 Although there have also been clinical studies of memantine in depressed patients, the results have not been promising. In a double-blind, placebo-controlled study, memantine was found to have no significant antidepressant Perifosine clinical trial effect in MDD patients.7 The reasons for the lack of response are unclear, but could be related to the dose of memantine, or Inhibitors,research,lifescience,medical the route and time course of administration. For example, memantine was administered orally at an escalating dose over several weeks; it would be interesting Inhibitors,research,lifescience,medical to determine if intravenous dosing, similar to that for ketamine, would be more efficacious and rapid, ft is also notable that memantine is a low-affinity open-channel antagonist that is trapped at a lower rate (70%) compared with ketamine.64 AZD6765 Another nonselective NMDA antagonist that has been

tested as an antidepressant is AZD6765. This compound is reported to have antidepressant actions in rodent models.69 Moreover, AZD6765 has a reasonable safety profile Inhibitors,research,lifescience,medical in humans and does not induce psychotomimetic side effects. This compound was developed as a neuroprotective agent for the treatment of stroke, but lack of efficacy halted further development. However, Inhibitors,research,lifescience,medical a recent clinical study demonstrates that AZD6765 produces a rapid antidepressant response in depressed

patients.69 fn this study, which was conducted with patients considered treatment-resistant (ie, based on their lack of response to typical antidepressants), approximately one third showed a rapid and significant antidepressant response within 80 minutes Inhibitors,research,lifescience,medical of a single treatment. A recent study has reported that repeated dosing of AZD6765 (3 times a week for 3 weeks) produces an antidepressant response after 1 to 2 weeks of treatment.70 The only side effects reported were mild, transient dizziness and headaches. This relatively mild side-effect profile, particularly with regard to psychotomimetic and dissociative effects, could be related to the low proportion of AZD6765 that is trapped in the pore (54%) relative to ketamine (82 %).69 Together, these studies indicate that AZD6765 has a relatively rapid onset of action, with fewer side effects than ketamine. only GLYX-13 GLYX-13 is a tetrapeptide that acts as a partial agonist at the glycine site of the NMDA receptor complex, making this agent unique among the drugs acting at NMDA receptors that are being investigated for antidepressant activity. Originally designed to enhance learning and memory, subsequent studies have demonstrated that GLYX-13 produces rapid antidepressant actions in rodent models and in depressed patients.

Figure 22 Glia cells do not exhibit cytoplasmic abnormalities.

(A and B) At P30, both astrocytes (A) and oligodendrocytes (O) appear to have normal mitochondria (arrowheads) and cytoplasm, although swollen mitochondria can be seen in surrounding neuropil. (C and … this website Initial NMJ denervation is associated with motor deficits Previous gait analysis of SOD1G93A mice have indicated supranormal gait prior to neurodegeneration and the onset of gait disturbances at ~13 weeks of age, when the animals were tested walking horizontally at speeds of 24 and 36 cm/sec (Amende et al. 2005). We did Inhibitors,research,lifescience,medical not detect any overt deficits in gait when SOD1 mice voluntarily traversed the walking compartment floor. Initial clinical symptom onset of ALS in patients often occurs as small and subtle changes in muscle Inhibitors,research,lifescience,medical strength (e.g., occasional foot drop, difficulty turning a key, slurring of speech). It is difficult to assess these kinds of changes by simple observation of mouse behavior. We therefore challenged the animals with a more rigorous treadmill walking protocol. The treadmill, walking compartment, and camera system were pitched at an angle so that the animals walked up an incline Inhibitors,research,lifescience,medical of 15 degrees and the motor speed was set to 40 cm/sec. Under these conditions there

was a significant increase in the variability of hindlimb Inhibitors,research,lifescience,medical paw placement angle in SOD1 mice at P28 and P30 (Fig. ​(Fig.23).23). We believe that the variability of hind paw placement angle corresponds to muscle weakness due to initial denervation that occurs in the TA as reported in this study and medial gastrocnemius muscle in a previous study (Gould et al. 2006). These behavior changes may Inhibitors,research,lifescience,medical also reflect denervation in other hindlimb muscles that were not studied (e.g.,

extensor digitorum longus). The difference in paw placement angle tends to disappear by P40. At the same time the differences in hindlimb stance width become more prominent and increases with age. There was also an apparent decrease in hindlimb stance width at P32, Tryptophan synthase although the difference between SOD1 and WT was not statistically significant until P40; a decrease in forelimb stance width was also detected at day 40 (Fig. ​(Fig.23).23). These more profound changes correspond with increased muscle denervation that occurs with disease progression. Figure 23 SOD1G93A mice exhibit deficits in motor function that correlate with early muscle denervation. (A) Schematic of forelimb and hindlimb stance width in WT and SOD1G93A mice walking 40 cm/sec up an incline (~15 degrees). Forelimb stance width is … Using the loaded grid test as an assay of forelimb muscle strength, SOD1 mutant mice at P29 (but not at P27 or P28) exhibited the first signs of muscle weakness as indicated by a significantly decreased duration of time before dropping a 15 g weight.

While infants have been shown to be able to bind object and location in other studies

(Káldy and Leslie 2003), it seems that they are not yet fully capable of quickly recognizing and remembering more objects in specific locations. The ability to quickly bind multiple objects to specific locations within an environment is a prerequisite for using Inhibitors,research,lifescience,medical landmarks during navigation. Therefore, young infants’ incapability to successfully use landmarks (e.g. Newcombe et al. 1998; Balcomb et al. 2011) may be the result of an inability to process multiple objects in an environment. Alternatively, the delay in landmark use as compared to object recognition could be caused by the infants’ inability to retain object information in memory over time (Richmond and Nelson 2007). Computerized environments can be used to investigate whether the prolonged development of memory for objects causes

the delay between the detection of object changes and the use of Inhibitors,research,lifescience,medical landmarks in navigation or whether this delay is related to the later onset of fast detection of binding objects to specific locations within an environment. Acknowledgments This research was supported by the Netherlands Organization for Scientific Research (Vidi-Grant 452-07-015 to G. J.) and by the European Commission (ERC Inhibitors,research,lifescience,medical Starting Independent Researcher Grant 204643 to G. J.). We thank Clemens Jansen and Nathalie Veenendaal for their assistance with data collection, the staff of the Baby Research Centre Inhibitors,research,lifescience,medical for assistance in the recruitment of the participants, and Jamie Edgin for her helpful comments on an earlier version of this manuscript. Conflict of Interest None declared. Supporting Information Additional Supporting Information may be found in the online version of this article: Figure S1. Complete stimulus set in each environment. Figure S2. Grand average waveform at Oz for all conditions after onset of stimulus, showing onset and offset visual evoked potentials. Figure S3. Grand Inhibitors,research,lifescience,medical average waveforms at the five fronto-central electrodes for the standard condition showing no difference in amplitude when different

number of trials was included in the waveform. The Ketanserin blue line represents the standard as used in the analysis. The red line represents the mean of all standards that were directly followed by an odd stimulus. The green line includes every third presentation of a standard followed by an odd stimulus, to match the number of trials in the odd conditions. Click here to view.(9.3M, tif) Click here to view.(7.4M, tif) Click here to view.(18M, tif)
In addition to the motor dysfunctions caused by Parkinson’s disease (PD) (e.g., resting tremor, muscle rigidity, bradykinesia, and postural instability), Selleckchem LY2835219 nonmotor dysfunctions such as psychiatric symptoms, dementia, sleep disorders, pains, and autonomic dysfunctions have recently been recognized (Ziemssen and Reichmann 2010; Jain 2011).

Based on the recent Fullanna et al81 data, it is clear that these individuals are at increased risk of developing OCD. Early interventions may be especially beneficial for these high-risk individuals. Longitudinal studies Variation between individuals at particular points in time can mask detection of potentially important, developmental shifts. Longitudinal studies Inhibitors,research,lifescience,medical examining changes in risk exposure, OC symptoms, comorbid disorders, particularly when linked

to performance on neuropsychological tests, brain processes, and immunological function. Looking at these changes over a developmental time frame is likely to be a fruitful approach, particularly when linked with the ability to explore potential genetic determinants.82 They have already proven their worth in studies of the temporal stability of OC symptom dimensions and psychosocial selleck chemical stress.70,81,83 It is increasingly Inhibitors,research,lifescience,medical clear that obsessions and compulsions are common in the adult population, have their roots in childhood, and are associated with interference, risk for comorbid disorders, and help-seeking.81 Longitudinal analyses could also have important implications in refining therapeutic decisions. Longitudinal studies of high-risk

individuals Inhibitors,research,lifescience,medical who do not develop psychopathology may be especially valuable in elucidating protective factors, and serve as the basis for developing novel therapeutics. Genetic studies A dimensional approach may be particularly valuable for genetic studies, where it increasingly seems that, some vulnerability genes may be shared by more than a single disorder, and that subthreshold cases are likely Inhibitors,research,lifescience,medical to be found in family members. An initial confirmation of this approach comes from the recent study by Hasler and colleagues,84 Inhibitors,research,lifescience,medical which collected data from 418 sibling pairs with OCD. Among potentially relevant comorbid conditions for genetic studies, they found that bipolar I/II

and major depressive disorder were strongly associated with the Forbidden thoughts factor, whereas ADHD, alcohol dependence, and bulimia were associated with the Symmetry factor. Twin and family studies suggest that genetic factors play a role in the expression of OCD.85 Recent, advances in molecular genetics have greatly much increased the capacity to localize disease genes on the human genome. These methods are now being applied to complex disorders, including OCD. Although earlier studies have indicated that the vertical transmission of OCD in families is consistent with the effects of a single major autosomal gene, it is likely that there are a number of vulnerability genes involved. One of the major difficulties in the application of these approaches is the likely etiologic heterogeneity of OCD and related phenotypes. Heterogeneity reduces the power of gene-localization methods, such as linkage analysis.

Finally, estradiol concentrations remain normal or arc elevated during the perimenopausal period, suggesting that, the ovary remains capable of secreting this critical hormone. Interestingly, these findings are strikingly similar to what has been observed in middle-aged laboratory rodents, as they become less fertile and cease to have reproductive Inhibitors,research,lifescience,medical cycles.2 Since many studies to examine the role of the brain cannot be performed in women because they are invasive and involve experimental manipulations that, cannot be performed

in humans, laboratory animals provide the only means through which we can gain a better understanding of the role of the brain in the menopause. The striking similarities between many of the events that occur during middle age give us reason to believe that rodents serve as excellent models in which to examine the factors that initiate the process of reproductive aging during middle age. We hope that information gained from these species can be extrapolated Inhibitors,research,lifescience,medical to humans and Inhibitors,research,lifescience,medical will

allow us to uncover and explore concepts that can be generalized to human reproductive aging. Estrogen Olaparib cell line replacement therapy in postmenopausal women The process of reproductive aging in women ultimately results in a hypoestrogenic, postmenopausal state. As our understanding of estrogen action in the body grows, the consequences of prolonged hypoestrogenicity and the profound impact of estrogen replacement therapy (ERT) on postmenopausal women become increasingly clear. We now know that, although estrogen can promote disease Inhibitors,research,lifescience,medical in some women,3 it acts in a broad spectrum of tissues to promote health and overall well-being.4-8 Insight into many of the protective actions of estrogen is gained from observations that oophorectomized Inhibitors,research,lifescience,medical young women suffer increased pathophysiology, such as bone resorption,9 compared with their counterparts with normal reproductive function. Further, hypoestrogenic, postmenopausal women often suffer

increased disease compared Thalidomide with premenopausal women and age-matched men. Studies demonstrate that estrogen acts in the brain to enhance cognitive function and decrease the risk and/or delay the onset of neurodegenerative conditions.6,10-13 Further, estrogen decreases the risk and/or mortality for cardiovascular disease, potentially through its beneficial effects on the lipid profile and on the endothelium,7,14,15 though recent evidence suggests that estrogen-mediated protection of the heart may not persist in women with preexisting cardiovascular disease.16 Finally, estrogen is crucial in the positive remodeling of bone; the loss of estrogen in postmenopausal women is accompanied by a dramatic increase in osteoporosis.