These data support the hypotheses that PD patients exert nonmotor

These data support the hypotheses that PD patients exert nonmotor symptoms and morbidities in the early years after a diagnosis and in the years before a

diagnosis. The genitourinary CYT387 datasheet system diseases manifested themselves as prostatic hypertrophy (OR = 1.30) and increased urinary infection (OR = 1.30), which we believe is caused by autonomic Inhibitors,research,lifescience,medical dysfunctions (Winge and Fowler 2006). The effects on the digestive system consisted of more frequent constipation (OR = 1.57), suggesting decreased gastrointestinal mobility probably due to dysfunctional autonomic activity (Winkler et al. 2011), associated with the accumulation of alpha-synuclein in the intestinal neurons (Lebouvier et al. 2009).The associations of PD with mental and behavioral disorders are well-known and represent other, nonmotor control areas of the brain affected Inhibitors,research,lifescience,medical by neurodegeneration. We found that PD was associated with mental and behavioral disorders prior to diagnosis. Depression and cognitive complaints have been reported (Dissanayaka

et al. 2011), and are probably due to the early involvement of the raphe nuclei. No single diagnosis in the mental and behavioral disorders group had a frequency of above 1% in either group and was, therefore, excluded in the dataset. A particularly interesting finding was the significantly higher risk of falls Inhibitors,research,lifescience,medical before diagnosis, even when we adjusted for age, gender, and social factors. Accidental falls are common in the elderly (Gillespie et al. 2009). Due to the type of motor, nocturnal, and autonomic involvement, we would expect truncal instability for PD to result in more falls and accidents. Even before diagnosis, PD patients were more likely to experience head traumas (OR = 1.78). We have no information about the cause Inhibitors,research,lifescience,medical of accidents

(e.g., while supine, nocturnal, etc.), but we suggest that the high incidence of injuries (Duncan et al. 2012) may be attributed to the combined effect of autonomic dysfunction, nocturnal motor/behavioral (REM sleep behavioral disorder) (Suzuki et al. 2011), motor involvement with truncal instability, and cognitive involvement Inhibitors,research,lifescience,medical (Aarsland and Kurz 2010b). Another important consequence is that physicians should be aware of potential neurodegenerative disorders in patients who present with falls and injuries, especially if the injuries are serious, for example, much to the head and face. It should be noted that we cannot rule out the possibility that a head trauma in itself increases the risk of developing PD, as has been proposed elsewhere (Goldman et al. 2012). However, if we include other injuries (hip, shoulder, face, etc.), as is possible in this study, the causal route is most likely that the increase in falls is caused by early truncal instability, autonomic dysfunction, and slow reaction time that predates the development of symptoms severe enough to be categorized as PD.

The second group of study participants included mechanically vent

The second group of study participants included mechanically ventilated CHF patients with the same ventilator settings and same tidal volumes before and after clinical improvement. This sample was enrolled to control for the variable tidal volumes. The third group was a control group of healthy subjects with no known cardiopulmonary disease and normal chest

Inhibitors,research,lifescience,medical radiographs (as per official report). Recording Procedure and Data Analysis For the CHF patients, respiratory sound data was acquired on the day of presentation to the ED and again on the day of discharge. For the mechanically ventilated CHF patients, respiratory sound data was acquired when chest radiographs showed pulmonary edema and again before extubation when radiographs demonstrated an improvement in pulmonary edema. All recordings were obtained with the subjects in the seated position. The tidal volumes of the non-ventilated patients Inhibitors,research,lifescience,medical in this study were not measured; patients were instructed to take comfortable deep breaths for all recordings. All measurements were performed by one individual who followed a standardized protocol to obtain vibrational images.

This individual was also blinded to the clinical and radiologic information of subjects. Respiratory sounds Inhibitors,research,lifescience,medical were captured using a vibration response imaging device (Deep Breeze™, Or-Akiva, Israel). This is a non-invasive computerized acoustic-based imaging technique that displays the geographic distribution of vibration energy of respiratory sounds throughout the respiratory cycle [4,5]. With this technique, 36 sensors (two arrays, one array over each Inhibitors,research,lifescience,medical lung) were adhered to the patient’s back in a sitting position by a computer-controlled low vacuum and record the respiratory sound patterns. Subjects were instructed to take deep, comfortable breaths during Inhibitors,research,lifescience,medical 20 seconds of recording. Data MAPK Inhibitor Library solubility dmso collected by the sensors were processed and a grayscale video depicting

the relative geographical distribution of respiratory sound was created. Each frame of the video was created from 0.17 seconds worth of data. The maximal energy frame was the frame in the video sequence that usually provided the most information on the distribution of lung vibration and usually approximated peak inspiration. The image STK38 from this frame was used for the area measurements. The image represents the relative distribution of vibration energy, not the absolute energy. A larger image indicates a more homogeneous distribution of vibration intensity throughout the lung and a smaller image a more focal distribution (Figure ​(Figure11). Figure 1 Vibration energy image. 36 vibration response imaging (VRI) sensors are spaced over the patient’s back and detect vibrations during respiration. The size of the dots is a cartoon representation of the amount of vibration energy detected by that sensor. …


A previous study by Little et al.12) showed decreased AVA by acute BP elevation induced by phenylephrine infusion and hand grip exercise. They suggested that the impact of BP change is associated with transvalvular flow rate through aortic valve without relation to SVR or SAC. In this study, we adopted Pcom instead of hand grip exercise or phenylephrine infusion because

these methods augment Inhibitors,research,lifescience,medical heart rate and induce a significant change in ejection time, as previously described. Because our study was free from changes in HR and LV ejection time under Pcom, an impact of LV afterload change on AVA assessment can be exclusively assessed, which is, we believe, a significant advantage of the current study. LIMITATIONS Pcom is a useful method to increase LV afterload without change of preload or HR when compared to other methods, Inhibitors,research,lifescience,medical such as hand grip exercise or phenylephrine infusion.12) However, Pcom possibly increases the venous return from lower extremities, which could explain, to some extent, increased E velocity, and slightly increased LV end-diastolic dimension. However, Inhibitors,research,lifescience,medical a previous study clearly

demonstrated that the primary mechanism whereby Pcom induced changes in hemodynamics is through an acute increase in LV afterload.13) In addition, a change in LV CO was minimal, highlighting the impression that hemodynamic effect by venous return for cardiac performance was, if any, negligible. Simulation of arterial BP elevation by Pcom also has a limitation for SVR increase alone, and cannot increase Inhibitors,research,lifescience,medical aortic stiffness which is more important

in essential hypertension in elderly patients. We also cannot directly measure LV systolic wall stress and central BP, because we did not perform invasive monitoring of intra-LV pressure and central BP, however, SVR and SAC that were employed in the current study were previously p38 kinase assay validated against invasively obtained hemodynamic data as indirect indexes for LV afterload.14),15) CONCLUSIONS Assessment of AS severity by routine transthoracic echocardiography was Inhibitors,research,lifescience,medical not significantly influenced by a change in LV afterload. AV Vmax could be slightly decreased PAK6 when LV afterload rises, but these changes did not seem to exert a significant influence on clinical decision making in managing AS patients. EOAAV and Doppler velocity index is more stable method for evaluation of AS severity than AV Vmax, and therefore these 2 indexes should be used in the determination of AS severity, rather than AV Vmax or TPG of AV. Acknowledgements This study was supported by an Industry-Academy grant of the Korea Society of Echocardiography (2008, Chang SA).
In a mitral valve with functional MR, geometric abnormalities of incomplete valve coaptation at systole are mainly characterized by leaflet tethering due to displacement of PMs and flattening of mitral annulus.

The role of personality disorders within the legal arena has been

The role of personality disorders within the legal arena has been of interest to clinicians since the early days of psychiatry when physicians were called to court in an effort to explain criminal behaviors.1 Clinical and legal interest, as well as fascination of the general public about understanding why people are involved in crime and other behaviors that offend, astound, harm, or frighten, continues to the present day.2-4 Though it is often thought that this understanding remains the province of forensically trained psychiatrists or psychologists applying specialized skills to evaluating individuals Inhibitors,research,lifescience,medical who have entered the criminal justice system or claim to have been civilly wronged,

there is no specific prohibition against any clinician providing expertise within the legal system. Many do so regularly in the contexts of involuntary commitment or assessing competency to make treatment decisions, Inhibitors,research,lifescience,medical or are asked by attorneys or the courts to share their specific content-related expertise. It is very common for questions to arise in these settings as to what significance,

if any, should be given to the presence of personality Inhibitors,research,lifescience,medical disorders. selleck chemical mental illnesses, including personality disorders, can potentially modify applications of the law in criminal and civil contexts. Classification and specific definitions of mental disorders can have a major impact on how and when they serve as modifiers.5 The legal system’s perception of mental illness is defined by society, and it is the application of that understanding to a specific person or fact pattern that defines the relationship between mental illness and the law. Clinicians entering the forensic arena, however, Inhibitors,research,lifescience,medical for the most part, do not immerse themselves in thinking about Inhibitors,research,lifescience,medical the current social definition or understanding of mental illness. Because of their training and experience, clinicians most often resort to explaining mental illness through the lens of the most widely accepted classification system, which for the last 40 years, at least in the United States, has been the latest version

of the Diagnostic and Statistical Manual of Mental Disorders (DSM). To date, the DSM6 has utilized a categorical approach to personality disorder diagnoses, in that an individual must meet specific criteria in order to be categorized as having a personality disorder. But the DSM has cautioned clinicians and researchers (its intended science user audiences) that inclusion of diagnostic categories does not implythat they meet legal criteria for what constitutes mental disease, disorder, or disability: “The clinical and scientific considerations involved in categorization of these conditions as mental disorders may not be wholly relevant to legal judgments, for example, that take into account such issues as individual responsibility, disability determination, and competency.

Maimonides himself addresses these Jewish rules:13 We may not sha

Maimonides himself addresses these Jewish rules:13 We may not shave the corners of our heads as the idolaters and their priests do, as Leviticus [19:27] states: “Do not cut off the corners of your heads.” One may remove [the hairs from] the corners [of our heads] with scissors. The prohibition applies only to total removal with a razor. Did King David

have visible Pe-ot as we now know them? Did the rabbis of the Mishna? Did Maimonides? The evidence is wholly against it. Maimonides had most probably kept his side curls mildly trimmed by scissors rather than fully shaved as depicted in the portrait. Full-grown Pe-ot originated only in the sixteenth century when it became socially #INCB024360 keyword# important for observant Jews effectively to distinguish Jews from non-Jews and, more importantly, Jews from other Jews who were thought to be too modern. Whoever drew the Maimonides portrait was not aware that completely shaven side curls and a trimmed beard are in fact characteristic of Islamic figures. Alternatively, Inhibitors,research,lifescience,medical the artist may have assumed that because of his high ranking

and frequent encounters with kings and ministers Maimonides must have worn clothes that resembled Inhibitors,research,lifescience,medical Islamic clothes as well as shaved and trimmed his facial hair like distinguished Islamic figures. Interestingly, Maimonides has indeed allowed this in rare circumstances like his:14 A Jew who has an important position in a gentile kingdom and must sit before their kings, and would be embarrassed if he did not resemble them, is granted permission to wear clothes which resemble theirs and shave the hair on his face as they do. The artist may have even deliberately drawn Maimonides to appear as a Muslim scholar in order to appeal Inhibitors,research,lifescience,medical to non-Jewish audiences and emphasize the influence of Islamic culture, science, and medicine on Maimonides rather than Inhibitors,research,lifescience,medical his Jewish origin and education. Key figures engaged in circulating the Maimonides portrait in Europe in the eighteenth and nineteenth centuries were mostly leaders of the Jewish Enlightenment

movement (Haskalah in Hebrew). Haskalah advocated adopting enlightenment values, pressing for ANNUAL REVIEWS better integration into European society, and increasing education in secular studies, Hebrew language, and Jewish history. Haskalah in this sense marked the beginning of the wider engagement of European Jews with the secular world, ultimately resulting in the first Jewish political movements and the struggle for Jewish emancipation. Maimonides’ portrait lacking characteristic Jewish features was in line with their motto “Be a Jew at home, and a man in the street”. It is of interest to note that, unlike in the portrait, in the renowned statue in Cordoba (Figure 11) Maimonides does appear to have side curls. This may reflect the artist’s perception of prominent, especially religious, Jews.

Rarely, severe infections have been reported [70] Confusion abou

Rarely, severe infections have been reported [70]. Confusion about whether an envenomated extremity is inflamed or infected may lead to unnecessary medical care, including intravenous antibiotics and prolonged hospitalization [71]. Decisions about debridement and tissue grafting may also be complex. Consultation with an expert who has experience managing envenomated wounds may improve these decisions. Treatments to avoid in pit viper snakebite (box 15) The panel recommends against several therapies that are commonly utilized to treat crotaline envenomation, but which are ineffective, unnecessary, or harmful.

Wound incision and suction Inhibitors,research,lifescience,medical does not remove meaningful amounts of venom and can worsen local Inhibitors,research,lifescience,medical tissue injury [72,73]. Although little evidence exists to condemn the topical application of ice, this measure appears to be ineffective [74]. More aggressive forms of cryotherapy, such as ice water immersion, have been associated with severe iatrogenic tissue injury [75]. Although this issue has not been subjected to study, panel members recommended avoiding the use of non-steroidal

anti-inflammatory Inhibitors,research,lifescience,medical drugs (NSAIDs) because of the theoretical harm associated with the platelet dysfunction caused by NSAIDs in a potentially thrombocytopenic patient. Prophylactic antibiotics, prophylactic fasciotomy, and the routine use of blood products should be avoided for the reasons discussed above. Application of electrical current from a spark plug or hand-held “stun gun” has been recommended for therapy based on anecdotal experience from

a missionary physician in Ecuador[76]. Subsequent animal research and human Inhibitors,research,lifescience,medical experience have shown this practice to be ineffective and associated with significant tissue injury [77-81]. There is a paucity of data about the role of corticosteroids in crotaline snakebite. Based on unpublished experience and controlled trial data from the United States showing that corticosteroids do not improve Inhibitors,research,lifescience,medical outcome in old world viper (family Viperidae, subfamily Viperidae) envenomation, administration of corticosteroids is reserved for treatment of hypersensitivity phenomena [82,83]. Although data from envenomations by snakes native to the United States Cediranib (AZD2171) are lacking, arterial tourniquet application is ineffective and sometimes associated with apparent harm when used to treat South selleck chemicals llc American crotaline snakes [84]. Although pressure immobilization has a confirmed role in the management of highly neurotoxic elapid snake envenomations, its role in crotaline envenomation is unclear. In porcine models of severe western diamondback rattlesnake envenomation, pressure immobilization prolonged survival, with varying effects on local tissue injury [85,86].

Signs of crotaline envenomation (box 2) Approximately 80% of pit

Signs of crotaline envenomation (box 2) Approximately 80% of pit viper bites result in the injection of venom [17,18]. Pit viper venom is a complex mixture of proteins and other macromolecules, with more than 50 identified components. The clinical effects produced by envenomation can be broadly classified into three groups. Local tissue

Inhibitors,research,lifescience,medical effects include soft tissue necrosis and chemically mediated inflammation. A number of venom components, learn more including myotoxic phospholipases A2 such as crotoxin, venom metalloproteinases that activate tumor necrosis factor-alpha (TNF-α), myotoxin a, hyaluronidase, phosphomonoesterase, phosphodiesterase, arginine ester hydrolase, and histamine- and bradykinin-like factors, cause direct tissue injury and produce a broad cytokine response in the victim [7,19-22]. Clinically, these effects are evident as pain, redness, swelling, tenderness, and myonecrosis that Inhibitors,research,lifescience,medical begin adjacent to the bite site and spread with movement of the venom through the lymphatic system. More than 90% of envenomated pit viper victims develop Inhibitors,research,lifescience,medical local tissue effects [7]. Hematologic venom effects include fibrinogen degradation and platelet aggregation and destruction [23,24]. On a laboratory basis, these are manifest by decreased fibrinogen levels, elevated prothrombin time, and thrombocytopenia. Detection of fibrin split products may be an early sign

of a hematologic venom effect, and is a sensitive predictor of subsequent coagulopathy. In prospective studies, the presence of fibrin split products

within the first 12 hours of treatment Inhibitors,research,lifescience,medical predicted subsequent hypofibrinogenemia with 87% sensitivity and 69% specificity [25]. In some patients, elevated fibrin split products were the only early signs of developing hypofibrinogenemia. Clinically, oozing of blood from the bite site and ecchymosis of the surrounding tissue are common. Systemic bleeding Inhibitors,research,lifescience,medical may manifest as nuisance bleeding, such as gingival bleeding or haemolacria, or more serious bleeding, such as significant epistaxis, gastrointestinal bleeding, or intracranial hemorrhage. Even among the population with severe defibrination or thrombocytopenia, most patients do not develop medically significant bleeding Metalloexopeptidase [26]. However, severe and fatal bleeding complications have been reported [27-31]. Systemic venom effects include hypotension from direct cardiovascular toxicity, third-spacing and vasodilatation, nausea and vomiting, angioedema, and neurotoxicity. Many pit vipers envenomations can cause patients to experience a metallic taste and localized neuromuscular effects (fasciculation and myokymia). Severe systemic neurotoxicity induced by Mojave toxin A, including cranial neuropathy and flaccid paralysis, are frequent manifestations from Mojave rattlesnake (Crotalus scutulatus) and Southern Pacific rattlesnake (C.

In all patients, pulmonary symptoms resolved after cessation of t

In all patients, pulmonary symptoms resolved after cessation of the drug. Pulmonary hypertension is another adverse effect of IFN therapy in HCV-infected patients and has been repeatedly reported by different authors. Dhillon et al.45 reported 4 cases of irreversible pulmonary hypertension that developed after IFN therapy in HCV-infected patients. One of the patients was a 35-year-old male liver transplant recipient who developed pulmonary hypertension Inhibitors,research,lifescience,medical after IFN therapy for HCV and died about 2.5 years later, with no response to treatments. The second was a 40-year-old female

HCV-infected individual who developed pulmonary hypertension 32 click here months after IFN therapy. Although the treatments failed to reverse her hypertension, she Inhibitors,research,lifescience,medical was stabilized. The third patient was a 50-year-old male liver transplant recipient who developed pulmonary hypertension after 10 months of IFN therapy. Although his hypertension did not respond to therapy, his clinical condition stabilized. The fourth patient was a 49-year-old male HCV-infected person who developed pulmonary hypertension 8 months after IFN initiation. The therapy was Inhibitors,research,lifescience,medical not successful in treating the hypertension, however the patient was

stabilized. Ischemia in the Gastrointestinal Tract Ischemia in the gastrointestinal tract is another peripheral vascular Inhibitors,research,lifescience,medical disorder associated with IFN therapy in HCV-infected patients.52 Leung et al.53 have reported an interesting case of ischemic colitis that developed 34 weeks after PEG-IFN-alpha; the patient’s symptoms rapidly resolved with the cessation of therapy. Similar observations were reported by Tada et al.,54 who presented 2 cases of IFN-alpha-induced ischemic colitis that developed 2 and 6 months after IFN administration. Both cases had complete resolution two weeks after cessation of IFN therapy. A recent case report by Baik et al.55 showed the development of ischemic colitis 19 weeks after the commencement of PEG-IFN-alpha-2a and Ribavirin

therapy; the case was thoroughly cured only with Inhibitors,research,lifescience,medical cessation of the drug. However, not all cases of ischemia in the gastrointestinal tract had benign courses. Pompili et al.56 introduced a 53-year-old male with HCV infection who Histone demethylase developed jejunal ischemia 3 months after the initiation of therapy with PEG-IFN. Although the patient underwent emergent jejuna resection, he died 6 months after surgery due to preoperative complications. A case of phlegmonous colitis that developed in a chronic HCV-infected patient who received combined therapy of PEG-IFN and Ribavirin also had a lethal consequence.57 A case of neutropenic enterocolitis that developed 22 weeks after the initiation of PEG-IFN-alpha-2a and Ribavirin had a fatal outcome.58 Other Systemic Complications Induced by Interferon (IFN) Therapy Wang et al.

In addition, a group of AD patients (20 subjects) was established

In addition, a group of AD patients (20 subjects) was established as

a control group who continued receiving psychotropic drugs, and whose background characteristics were consistent with those of the patients in the group that received memantine (18 subjects). The patients were receiving psychotropic drugs before they received memantine. Furthermore, Inhibitors,research,lifescience,medical all of the subjects who participated in this study were inpatients whose treatment compliance had been confirmed each time by nurse or caregiver, and whose treatment compliance was thus assured. They were required to be symptomatically stable, as judged by the treating psychiatrist, to be able to complete all of the clinical measures. The study was an open-labeled, flexible-dose, naturalistic observational trial of AD patients undergoing the usual care and who required a change in their medication because of persistent symptoms or troublesome side effects. The control group had persistent symptoms or side effects. Inhibitors,research,lifescience,medical Patients had high scores in the neuropsychiatric inventory (NPI), even though they were considered stable.

However, there patients could not be considered refractory to psychotropic drugs. Only patients or family (caregivers) who had provided voluntary informed consent in writing to participate in this study upon receiving a full explanation of the purpose and method of the study were enrolled, while patient EPO906 confidentiality was afforded all due consideration, as Inhibitors,research,lifescience,medical were ethical considerations. Therapy method Inhibitors,research,lifescience,medical Subjects received memantine in addition to their previous therapeutic medications. Subjects were given an initial dose of memantine 5 mg in addition to their previous therapeutic medications, and the memantine dose was increased by 5 mg increments at 2-week intervals in consideration of safety. After 6 weeks, the memantine dosage was increased as necessary to optimize

the dose, and wherever possible the dosages of psychotropic drugs were reduced. Subjects were prescribed memantine within the dose range of Inhibitors,research,lifescience,medical 10–20 mg/day. The psychotropic equivalents calculation table of Inagaki and Inada was used as a guideline for calculating psychotropic equivalents [Inagaki and Inada, 2006, 2012] when calculating PAK6 the baseline to postdose changes in the dosages of the concomitant psychotropic drugs, and the subjects’ daily dosages were calculated in terms of risperidone or diazepam equivalents. Assessment methods The following clinical assessments were performed both at baseline and at 16 weeks by the psychiatrist who was providing the actual therapy. The outcome measures assessed were BPSD and cognitive function. BPSD was assessed using the NPI [Cummings et al. 1994] and cognitive function was assessed using the mini-mental examination (MMSE) [Folstein et al. 1975]. Statistical analysis The Wilcoxon signed rank sum test was used to analyze efficacy and changes in the dosages of concomitantly used psychotropic drugs in memantine therapy.

Thus, the 5-HTTLPR polymorphism affects not only central 5-HT fun

Thus, the 5-HTTLPR polymorphism affects not only central 5-HT function, but also seems to be involved in the regulation of biobehavioral characteristics.57 The G-protein-β3 subunit (Gβ3) gene Neurotransmitter molecules do not cross the postsynaptic membranes, but induce a cascade of reactions via their initial binding to surface receptors within the postsynaptic membrane, which are often coupled to guanine-nucleotide-binding proteins (G proteins). These G proteins represent initial regulatory components in transmembrane signaling

and are thus key elements in signal transduction, regulating many biological responses.58 In one subunit of these Inhibitors,research,lifescience,medical G proteins, the Gβ3 subunit, a polymorphism was identified (a C to T exchange at position 825 in exon 10), which leads to the occurrence of a splice variant (Gβ3-s) with deletion of 41 amino acids. It is now fairly well established that the T allele of this polymorphism, which results in increased ion flux across the membrane and increased signal Inhibitors,research,lifescience,medical transduction, is associated with hypertension and obesity.59,60 However, this genetic variant is not just important for somatic disorders, because we also found an increased frequency of the T allele in patients with affective psychosis.61 In an extended sample, using the DNA of

201 patients with Inhibitors,research,lifescience,medical major depression without increased proportions of hypertensives, Inhibitors,research,lifescience,medical we were able to replicate our previous results of increased frequency of allele T and increase in TT homozygotes (χ2=14.8; df=2; P=0.0006). Thus, our results are consistent with the hypothesis that disturbances in the signal transduction cascade on the level of G proteins are involved as contributing factor in the pathophysiology

of major depression, despite its importance in essential hypertension.62 The ACE gene Angiotensin-converting enzyme (ACE) Inhibitors,research,lifescience,medical is a zinc metallopeptidase involved in blood pressure regulation via the angiotensin-renin cascade, generating angiotensin II (ATII) from angiotensin I, and via degradation of the powerful vasodilator bradykinin. However, the effects of this enzyme are not restricted to the vasculature, as several Caspase inhibitor clinical trial studies have demonstrated that ACE might also be involved in HPA axis regulation and catecholamine production via the generation of ATII63 and is thus required for sympathoadrenal activation during stress. ATM Kinase Inhibitor clinical trial Further evidence suggests an involvement of the brain renin-angiotensin system in regulation of mood, because of the colocalization of angiotensin with dopamine-synthesizing neurons,64 the fact that ACE is involved in the metabolism of the neuropeptide substance P, which, in turn, is supposed to play a role in depression,65 and the clinical observation that the application of ACE inhibitors in hypertensives can induce euphoric or depressive states.