Usefulness of delayed enhancement magnetic resonance imaging for detecting cardiac rupture caused by small myocardial infarction in a case of cardiac tamponade.

Delayed enhancement magnetic resonance imaging (DE-MRI) has excellent spatial resolution and compared with other cardiac imaging techniques it can detect a small myocardial infarction (MI) or a subendocardial infarction. A 76-year-old man was admitted for loss of consciousness because of cardiac tamponade. The cause of tamponade was unknown, but electrocardiography and blood test suggested a recent MI. The removal of 100 ml bloody fluid by immediate pericardiocentesis normalized his hemodynamics, and he regained consciousness. Neither echocardiography nor scintigraphy could determine the location of the MI or rupture, but DE-MRI clearly demonstrated a transmural enhancement in a very narrow range of the lateral wall of the left ventricle. Coronary angiography revealed a severely stenotic lesion in the obtuse marginal branch of the left circumflex artery. DE-MRI is a powerful tool for diagnosing small MI that are undetectable with other imaging. Therefore, DE-MRI should be applied in cases with cardiac tamponade by unknown causes.     

Impaired exercise-induced vasodilatation in chronic atrial fibrillation--role of endothelium-derived nitric oxide.

Exercise capacity is often reduced in patients with atrial fibrillation (AF), but very few studies have focused on changes in endothelial function as a potential mechanism for the exercise limitation. The present study used using venous occlusion plethysmography to investigate whether nitric oxide (NO)-mediated vasodilatation is attenuated during exercise in patients with AF by measuring forearm blood flow (FBF) in 10 patients at rest and immediately after 2 levels of rhythmic handgrip exercise, before and after inhibition of NO synthesis with N(G)-monomethyl-L-arginine (L-NMMA, 100 micromol). The measurements were repeated 1 day after restoration of sinus rhythm by cardioversion. FBF responses to graded doses of acetylcholine (ACh) were also observed before and after cardioversion. Heart rate decreased after cardioversion, but blood pressure did not change. FBF at rest was not affected by cardioversion, but at the highest level of exercise it increased from 28.4+/-2.3 ml x min(-1) x dl(-1) before to 39.4+/-3.2 ml x min(-1) x dl(-1) after cardioversion (p<0.05). L-NMMA significantly decreased FBF at rest (p<0.01) and depressed the increase in FBF response to exercise after (p<0.01), but not before cardioversion. The FBF response to ACh was also accelerated significantly after cardioversion. The present results provide new evidence that NO bioavailability is depressed at rest and during exercise in patients with AF.     

Citrulline increases cholesterol efflux from macrophages in vitro and ex vivo via ATP-binding cassette transporters

Reverse cholesterol transport (RCT) is a mechanism critical to the anti-atherogenic property of HDL. Although citrulline contributes to the amelioration of atherosclerosis via endothelial nitric oxide production, it remains unclear whether it affects RCT. This study was undertaken to clarify the effects of citrulline on expressions of specific transporters such as ATP binding cassette transporters (ABC)A1 and ABCG1, and the cholesterol efflux from macrophages to apolipoprotein (apo) A-I or HDL in vitro and ex vivo. Citrulline increased ABCA1 and ABCG1 mRNA and protein levels in THP-1 macrophages, translating into enhanced apoA-I- and HDL-mediated cholesterol efflux. In the human crossover study, 8 healthy male volunteers (age 30–49 years) consumed either 3.2 g/day citrulline or placebo for 1 week. Citrulline consumption brought about significant increases in plasma levels of citrulline and arginine. Supporting the in vitro data, monocyte-derived macrophages (MDM) differentiated under autologous post-citrulline sera demonstrated enhancement of both apoA-I- and HDL-mediated cholesterol efflux through increased ABCA1 and ABCG1 expressions, compared to MDM differentiated under pre-citrulline sera. However, the placebo did not modulate these parameters. Therefore, in addition to improving endothelium function, citrulline might have an anti-atherogenic property by increasing RCT of HDL.     

TG13 management bundles for acute cholangitis and cholecystitis

Bundles that define mandatory items or procedures to be performed in clinical practice have been increasingly used in guidelines in recent years. Observance of bundles enables improvement of the prognosis of target diseases as well as guideline preparation. There were no bundles adopted in the Tokyo Guidelines 2007, but the updated Tokyo Guidelines 2013 (TG13) have adopted this useful tool. Items or procedures strongly recommended in clinical practice have been prepared in the practical guidelines and presented as management bundles. TG13 defined the mandatory items for the management of acute cholangitis and acute cholecystitis. Critical parts of the bundles in TG13 include diagnostic process, severity assessment, transfer of patients if necessary, therapeutic approach, and time course. Their observance should improve the prognosis of acute cholangitis and cholecystitis. When utilizing TG13 management bundles, further clinical research needs to be conducted to evaluate the effectiveness and outcomes of the bundles. It is also expected that the present report will lead to evidence construction and contribute to further updating of the Tokyo Guidelines. Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.     

ACE2 deficiency induced perivascular fibrosis and cardiac hypertrophy during postnatal development in mice

In order to investigate the role of angiotensin-converting enzyme 2 (ACE2) in cardiac development, we examined the effects of ACE2 deficiency on postnatal development of the heart using ACE2-knockout (ACE2KO) mice. Heart samples of wild type (WT; C57BL/6J) mice and ACE2KO mice were taken at 1, 4, and 10 weeks of age. In WT mice, expression of ACE2 mRNA increased from 1 week to 10 weeks. A similar increase was observed in immunostaining of ACE2 in the heart, in which ACE2 was strongly expressed in coronary arteries. Compared with WT mice, heart weight was greater in ACE2KO mice at 4 weeks, and coronary artery thickening and perivascular fibrosis were also already enhanced from 4 weeks. Consistent with the increase of fibrosis, cardiac expression of collagen and TIMP was higher, and expression of MMP was lower in ACE2KO mice at 4 weeks. In addition, TGF-β mRNA was also higher, and lower expression of PPARγ mRNA was observed at 4 weeks in ACE2KO mice. These results suggest that ACE2 plays an important role in postnatal development of the heart, and that lack of ACE2 enhances coronary artery remodeling with an increase in perivascular fibrosis and cardiac hypertrophy already around the weaning period.     

Ventral premammillary nucleus as a critical sensory relay to the maternal aggression network

Maternal aggression is under the control of a wide variety of factors that prime the females for aggression or trigger the aggressive event. Maternal attacks are triggered by the perception of sensory cues from the intruder, and here we have identified a site in the hypothalamus of lactating rats that is highly responsive to the male intruder—the ventral premammillary nucleus (PMv). The PMv is heavily targeted by the medial amygdalar nucleus, and we used lesion and immediate-early gene studies to test our working hypothesis that the PMv signals the presence of a male intruder and transfers this information to the network organizing maternal aggression. PMv-lesioned dams exhibit significantly reduced maternal aggression, without affecting maternal care. The Fos analysis revealed that PMv influences the activation of hypothalamic and septal sites shown to be mobilized during maternal aggression, including the medial preoptic nucleus (likely to represent an important locus to integrate priming stimuli critical for maternal aggression), the caudal two-thirds of the hypothalamic attack area (comprising the ventrolateral part of the ventromedial hypothalamic nucleus and the adjacent tuberal region of the lateral hypothalamic area, critical for the expression of maternal aggression), and the ventral part of the anterior bed nuclei of the stria terminalis (presently discussed as being involved in controlling neuroendocrine and autonomic responses accompanying maternal aggression). These findings reveal an important role for the PMv in detecting the male intruder and how this nucleus modulates the network controlling maternal aggression.Postpartum rats are highly aggressive toward other animals that enter the vicinity of their nest and pups, with the presumed function of protecting their offspring from harm (1). Maternal aggression is under the control of a wide variety of factors that prime the females for aggression or trigger the aggressive event. The priming of maternal aggression in laboratory rats relies first on the hormonal changes associated with late pregnancy and parturition, and then on exteroceptive stimulation from the pups (2–6). Maternal attacks are triggered by the perception of polymodal sensory cues from the intruder (7). Information from the main olfactory pathway is crucial for high maternal aggression, although any importance for accessory olfactory inputs is less clear (5, 6). Furthermore, somatosensory signaling from the perioral region of the dams’ face while they investigate an intruder is critical for attacks (8).Considering the overlap of sensory modalities involved in how offspring cues prime maternal aggression and those involved in how intruders trigger aggressive behavior, experimental approaches that permanently destroy a sensory system are difficult to interpret because the result observed could be due to altered priming or altered triggering of the behavior. For that reason, identifying a brain area that specifically responds to the intruder as a threat would clarify what sensory information is important for triggering maternal attacks and thus shed light on the neural organization of maternal aggression.The research on the neurobiology of maternal aggression has traditionally investigated individual brain sites and not often conceptualized the behavior as the outcome of activity of a much larger neural network. A region in the mediobasal hypothalamus, encompassing both the ventrolateral part of the ventromedial nucleus and adjacent regions of the subfornical lateral hypothalamic area, is critical for the expression of maternal aggression because electrolytic lesions therein practically abolished dam’s attacks on male intruders (9). It is notable that this part of the mediobasal hypothalamus corresponds to the caudal two-thirds of the so-called hypothalamic attack area (HAA), a region defined on functional grounds as the hypothalamic site with the lowest threshold to evoke aggressive responses (10). At this point, it is unclear how the sensory inputs priming or triggering maternal aggression influence this particular region of the HAA essential for the expression of aggressive behavior in lactating rats.To begin addressing what brain sites are involved in triggering maternal attacks, we have identified a site in the hypothalamus of lactating rats that is highly responsive to the male intruder—the ventral premammillary nucleus (PMv). We here used lesion and immediate-early gene studies to test our working hypothesis that the PMv signals the presence of a male intruder and transfers this information to the network organizing maternal aggression. Overall, the results help to unravel the basic neural organization of underlying maternal aggression, suggesting sites potentially involved in integrating priming and triggering events, and how those sites are related to the regions involved in the expression of aggressive behavior or its accompanying endocrine and autonomic responses.     

Decreased prevalence of celiac disease among Brazilian elderly

AIM: To evaluate the prevalence of celiac disease in a group of Brazilian individuals over 60 years of age and compare it with the previously known prevalence in a pediatric group living in the same geographical area.METHODS: The research protocol was approved by the Ethics Committee of the University of Brasilia School of Medicine, Brasilia, Brazil. Blood samples from 946 individuals (295 male and 651 female) aged 60 years or older were collected between May 2010 and July 2011. The study subjects’ mean and median ages were 68.1 and 67 years, respectively, ranging from 60 to 92 years. That age distribution closely corresponded to the age distribution of the Brazilian population according to the Brazilian 2010 census. The participants were consecutive and unselected outpatients undergoing blood tests at the University of Brasilia Hospital’s Clinical Pathology Laboratory. All sera were tested for immunoglobulin A anti-transglutaminase antibodies (IgA-tTG) by enzymelinked immunosorbent assay, and those that were positive were further tested for immunoglobulin A antiendomysium antibodies (IgA-EMA). Human leukocyte antigen (HLA) genotyping was performed for all individuals who exhibited positive serologic results for IgA-tTG and/or IgA-EMA.RESULTS: Out of the 946 studied patients, only one previously diagnosed case of biopsy-proven celiac disease was detected. For the remaining subjects, nine serum samples tested positive for IgA-tTG antibodies; however, none of them tested positive for IgA-EMA antibodies. The HLA genotyping of those nine subjects revealed that one was carrying DQA1*0501 and two were carrying DQB1*0201 alleles. These data showed that, among those 946 elderly individuals, the prevalence of celiac disease (CD) was 0.1% (95%CI: 0.00-0.59). The prevalence of CD for the elderly group was compared with that observed for the group of 2034 children younger than 15 years (age range, 1-14 years; mean age, 8 years) who took part in our previous CD prevalence screening study. All the children came from the s