Is persistent hypotension after transient cardiogenic shock associated with an inflammatory response?

We evaluated the recovery of cardiovascular function after transient cardiogenic shock. Cardiac tamponade was performed for 1 h and post-shock data were collected in 5 domestic large white female pigs (43 ± 5 kg) for 6 h. The control group (N = 5) was observed for 6 h after 1 h of resting. During 1 h of cardiac tamponade, experimental animals evolved a low perfusion status with a higher lactate level (8.0 ± 2.2 vs 1.9 ± 0.9 mEq/L), lower standard base excess (-7.3 ± 3.3 vs 2.0 ± 0.9 mEq/L), lower urinary output (0.9 ± 0.9 vs 3.0 ± 1.4 mL·kg-1·h-1), lower mixed venous saturation, higher ileum partial pressure of CO2-end tidal CO2 (EtCO2) gap and a lower cardiac index than the control group. Throughout the 6-h recovery phase after cardiac tamponade, tamponade animals developed significant tachycardia with preserved cardiac index, resulting in a lower left ventricular stroke work, suggesting possible myocardial dysfunction. Vascular dysfunction was present with persistent systemic hypotension as well as persistent pulmonary hypertension. In contrast, oliguria, hyperlactatemia and metabolic acidosis were corrected by the 6th hour. The inflammatory characteristics were an elevated core temperature and increased plasma levels of interleukin-6 in the tamponade group compared to the control group. We conclude that cardiovascular recovery after a transient and severe low flow systemic state was incomplete. Vascular dysfunction persisted up to 6 h after release of tamponade. These inflammatory characteristics may also indicate that inflammatory activation is a possible pathway involved in the pathogenesis of cardiogenic shock.

The immunomodulator glatiramer acetate influences spinal motoneuron plasticity during the course of multiple sclerosis in an animal model

The immunomodulador glatiramer acetate (GA) has been shown to significantly reduce the severity of symptoms during the course of multiple sclerosis and in its animal model - experimental autoimmune encephalomyelitis (EAE). Since GA may influence the response of non-neuronal cells in the spinal cord, it is possible that, to some extent, this drug affects the synaptic changes induced during the exacerbation of EAE. In the present study, we investigated whether GA has a positive influence on the loss of inputs to the motoneurons during the course of EAE in rats. Lewis rats were subjected to EAE associated with GA or placebo treatment. The animals were sacrificed after 15 days of treatment and the spinal cords processed for immunohistochemical analysis and transmission electron microscopy. A correlation between the synaptic changes and glial activation was obtained by performing labeling of synaptophysin and glial fibrillary acidic protein using immunohistochemical analysis. Ultrastructural analysis of the terminals apposed to alpha motoneurons was also performed by electron transmission microscopy. Interestingly, although the GA treatment preserved synaptophysin labeling, it did not significantly reduce the glial reaction, indicating that inflammatory activity was still present. Also, ultrastructural analysis showed that GA treatment significantly prevented retraction of both F and S type terminals compared to placebo. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which in turn may contribute to its neuroprotective effects during the course of multiple sclerosis.

Circadian cardiac autonomic function in perinatally HIV-infected preschool children

The 24-h heart rate variability and QT-interval adaptation was investigated in perinatally HIV-infected preschool children classified according to immunological status in order to assess autonomic function at early stages of infection. Thirty-five perinatally HIV-infected and clinically stable children (4.8 ± 0.3 years) were enrolled after approval of the study by the University Hospital Pedro Ernesto Ethics Committee and written informed parental consent was obtained. The children were classified according to peripheral CD4+ count (cells/µL) as follows: group 1, N = 11 (≥1000); group 2, N = 7 (≥500 and <1000); group 3, N = 17 (<500). Left ventricular ejection fraction (>55%), 24-h RR interval variability (RRV) indexes (NN, SDANN, SDNN index, r-MSSD) and 24-h QT and Bazett-corrected QT (QTc) were determined, and groups were matched for age, body surface area, and left ventricular ejection fraction, reducing biases in RRV. The peak differences (∆) between the highest and lowest RRV and QT indexes were extracted from nocturnal (1 am-6 am) and daytime (1 pm-6 pm) hourly assessed segments, respectively. Pearson’s correlation (r) and Kruskal-Wallis ANOVA were used to compare groups. CD4+ count correlated positively with ∆NN (r = 0.45; P = 0.003). There were no significant differences in daytime NN among groups. Nighttime SDNN index (P = 0.01), nighttime r-MSSD (P = 0.003), ∆NN (P = 0.01), ∆SDNN index (P = 0.03) and ∆r-MSSD (P = 0.004) were significantly lower in group 3 than in the other groups. Expected nighttime QTc-interval lengthening was not observed in all groups. In perinatally HIV-infected preschool children with preserved left ventricular systolic function, parasympathetic-mediated autonomic dysfunction parallels immune status, impairing both RRV and circadian QTc interval adaptation.

Cardioprotective effect of ornitho-kinin in an anesthetized, open-chest chicken model of acute coronary occlusion

The generation of bradykinin (BK; Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) in blood and kallidin (Lys-BK) in tissues by the action of the kallikrein-kinin system has received little attention in non-mammalian vertebrates. In mammals, kallidin can be generated by the coronary endothelium and myocytes in response to ischemia, mediating cardioprotective events. The plasma of birds lacks two key components of the kallikrein-kinin system: the low molecular weight kininogen and a prekallikrein activator analogous to mammalian factor XII, but treatment with bovine plasma kallikrein generates ornitho-kinin [Thr6,Leu8]-BK. The possible cardioprotective effect of ornitho-kinin infusion was investigated in an anesthetized, open-chest chicken model of acute coronary occlusion. A branch of the left main coronary artery was reversibly ligated to produce ischemia followed by reperfusion, after which the degree of myocardial necrosis (infarct size as a percent of area at risk) was assessed by tetrazolium staining. The iv injection of a low dose of ornitho-kinin (4 µg/kg) reduced mean arterial pressure from 88 ± 12 to 42 ± 7 mmHg and increased heart rate from 335 ± 38 to 402 ± 45 bpm (N = 5). The size of the infarct was reduced by pretreatment with ornitho-kinin (500 µg/kg infused over a period of 5 min) from 35 ± 3 to 10 ± 2% of the area at risk. These results suggest that the physiological role of the kallikrein-kinin system is preserved in this animal model in spite of the absence of two key components, i.e., low molecular weight kininogen and factor XII.

Ventricular performance and Na+-K+ ATPase activity are reduced early and late after myocardial infarction in rats

Myocardial infarction leads to compensatory ventricular remodeling. Disturbances in myocardial contractility depend on the active transport of Ca2+ and Na+, which are regulated by Na+-K+ ATPase. Inappropriate regulation of Na+-K+ ATPase activity leads to excessive loss of K+ and gain of Na+ by the cell. We determined the participation of Na+-K+ ATPase in ventricular performance early and late after myocardial infarction. Wistar rats (8-10 per group) underwent left coronary artery ligation (infarcted, Inf) or sham-operation (Sham). Ventricular performance was measured at 3 and 30 days after surgery using the Langendorff technique. Left ventricular systolic pressure was obtained under different ventricular diastolic pressures and increased extracellular Ca2+ concentrations (Ca2+e) and after low and high ouabain concentrations. The baseline coronary perfusion pressure increased 3 days after myocardial infarction and normalized by 30 days (Sham 3 = 88 ± 6; Inf 3 = 130 ± 9; Inf 30 = 92 ± 7 mmHg; P < 0.05). The inotropic response to Ca2+e and ouabain was reduced at 3 and 30 days after myocardial infarction (Ca2+ = 1.25 mM; Sham 3 = 70 ± 3; Inf 3 = 45 ± 2; Inf 30 = 29 ± 3 mmHg; P < 0.05), while the Frank-Starling mechanism was preserved. At 3 and 30 days after myocardial infarction, ventricular Na+-K+ ATPase activity and contractility were reduced. This Na+-K+ ATPase hypoactivity may modify the Na+, K+ and Ca2+ transport across the sarcolemma resulting in ventricular dysfunction.

Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species

Tolerance to lipopolysaccharide (LPS) occurs when animals or cells exposed to LPS become hyporesponsive to a subsequent challenge with LPS. This mechanism is believed to be involved in the down-regulation of cellular responses observed in septic patients. The aim of this investigation was to evaluate LPS-induced monocyte tolerance of healthy volunteers using whole blood. The detection of intracellular IL-6, bacterial phagocytosis and reactive oxygen species (ROS) was determined by flow cytometry, using anti-IL-6-PE, heat-killed Staphylococcus aureus stained with propidium iodide and 2',7'-dichlorofluorescein diacetate, respectively. Monocytes were gated in whole blood by combining FSC and SSC parameters and CD14-positive staining. The exposure to increasing LPS concentrations resulted in lower intracellular concentration of IL-6 in monocytes after challenge. A similar effect was observed with challenge with MALP-2 (a Toll-like receptor (TLR)2/6 agonist) and killed Pseudomonas aeruginosa and S. aureus, but not with flagellin (a TLR5 agonist). LPS conditioning with 15 ng/mL resulted in a 40% reduction of IL-6 in monocytes. In contrast, phagocytosis of P. aeruginosa and S. aureus and induced ROS generation were preserved or increased in tolerant cells. The phenomenon of tolerance involves a complex regulation in which the production of IL-6 was diminished, whereas the bacterial phagocytosis and production of ROS was preserved. Decreased production of proinflammatory cytokines and preserved or increased production of ROS may be an adaptation to control the deleterious effects of inflammation while preserving antimicrobial activity.

Spectral and symbolic analysis of the effect of gender and postural change on cardiac autonomic modulation in healthy elderly subjects

The objective of this study was to use linear and non-linear methods to investigate cardiac autonomic modulation in healthy elderly men and women in response to a postural change from the supine to the standing position. Fourteen men (66.1 ± 3.5 years) and 10 women (65.3 ± 3.3 years) were evaluated. Beat-to-beat heart rate was recorded in the supine and standing positions. Heart rate variability was studied by spectral analysis, including both low (LFnu-cardiac sympathetic modulation (CSM) indicator) and high (HFnu-cardiac vagal modulation (CVM) indicator) frequencies in normalized units as well as the low frequency/high frequency (LF/HF) ratio. Symbolic analysis was performed using the following indexes: 0V% (CSM indicator), 1V% (CSM and CVM indicators), 2LV% (predominantly CVM indicator) and 2ULV% (CVM indicator). Shannon entropy was also calculated. Men presented higher LFnu and LF/HF ratio and lower HFnu and 1V% symbolic index (57.56, 4.14, 40.53, 45.96, respectively) than women (24.60, 0.45, 72.47, 52.69, respectively) in the supine position. Shannon entropy was higher among men (3.53) than among women (3.33) in the standing position, and also increased according to postural change in men (3.25; 3.53). During postural change, the LFnu (24.60; 49.85) and LF/HF ratio (0.45; 1.72) increased, with a concomitant decrease in HFnu (72.47; 47.56) and 2LV% (14.10; 6.95) in women. Women presented increased CSM in response to postural change and had higher CVM and lower CSM than men in the supine position. In conclusion, women in the age range studied presented a more appropriate response to a postural change than men, suggesting that cardiac autonomic modulation may be better preserved in women than in men.

Dynamics of immunosuppression in hamsters with experimental visceral leishmaniasis

Immunosuppression has been reported to occur during active visceral leishmaniasis and some factors such as the cytokine profile may be involved in this process. In the mouse model of cutaneous leishmaniasis using Leishmania (Leishmania) major, the Th1 response is related to protection while the Th2 response is related to disease progression. However, in hamsters, which are considered to be an excellent model for the study of visceral leishmaniasis, this dichotomy is not observed. Using outbred 45- to 60-day-old (140 to 150 g) male hamsters infected intraperitoneally with 2 x 10(7) L. (L.) chagasi amastigotes, we evaluated the immune response of spleen cells and the production of cytokines. We used 3 to 7 hamsters per group evaluated. We detected a preserved response to concanavalin A measured by index of proliferation during all periods of infection studied, while a proliferative response to Leishmania antigen was detected only at 48 and 72 h post-infection. Messenger RNA from cytokines type 1 (IL-2, TNF-α, IFN-γ) and type 2 (IL-4, IL-10 and TGF-β) detected by reverse transcriptase polymerase chain reaction and produced by spleen cells showed no qualitative difference between control non-infected hamsters and infected hamsters during any period of infection evaluated. Cytokines were measured by the DNA band intensity on agarose gel using the Image Lab 1D L340 software with no differences observed. In conclusion, the present results showed an antigen-dependent immunosuppression in hamsters with active visceral leishmaniasis that was not related to the cytokine profile.

Modulation of murine blastocyst hatching in vitro by glutamine and tryptophan

Enrichment of culture media with amino acids improves embryo development. However, little is known about the specific action of each amino acid during embryogenesis. The present study was undertaken to examine the effect of L-glutamine (Gln) and tryptophan (Trp) on mouse embryo hatching, expansion and viability in vitro. Blastocysts were collected from 6- to 8-week-old female BALB/c mice (N = 30) and cultured in M2 medium containing either 0.125, 0.25 or 0.5 mM Trp, 1 mM Gln, or M2 alone. Gln significantly increased (100%; P < 0.05) blastocyst hatching at 24 h compared to M2 alone or Trp; moreover, Trp inhibited blastocyst hatching when compared to M2 alone (P < 0.05) at 72 h. In contrast, the percentage of embryos reaching the state of expanded blastocyst at 48 h was significantly higher in medium with 1 mM Gln (66.6%; P < 0.05) or with 0.125 mM Trp (61.1%; P < 0.05). Unexpectedly, Trp increased the percentage of degenerated blastocysts after 48 h (67.7%; P < 0.05), while Gln preserved blastocyst viability. These results suggest that Gln may enhance blastocyst hatching, expansion and viability in vitro.

Alternative pathways for angiotensin II generation in the cardiovascular system

The classical renin-angiotensin system (RAS) consists of enzymes and peptides that regulate blood pressure and electrolyte and fluid homeostasis. Angiotensin II (Ang II) is one of the most important and extensively studied components of the RAS. The beneficial effects of angiotensin converting enzyme (ACE) inhibitors in the treatment of hypertension and heart failure, among other diseases, are well known. However, it has been reported that patients chronically treated with effective doses of these inhibitors do not show suppression of Ang II formation, suggesting the involvement of pathways alternative to ACE in the generation of Ang II. Moreover, the finding that the concentration of Ang II is preserved in the kidney, heart and lungs of mice with an ACE deletion indicates the important role of alternative pathways under basal conditions to maintain the levels of Ang II. Our group has characterized the serine protease elastase-2 as an alternative pathway for Ang II generation from Ang I in rats. A role for elastase-2 in the cardiovascular system was suggested by studies performed in heart and conductance and resistance vessels of normotensive and spontaneously hypertensive rats. This mini-review will highlight the pharmacological aspects of the RAS, emphasizing the role of elastase-2, an alternative pathway for Ang II generation.

Lipoic acid, but not tempol, preserves vascular compliance and decreases medial calcification in a model of elastocalcinosis

Vascular calcification decreases compliance and increases morbidity. Mechanisms of this process are unclear. The role of oxidative stress and effects of antioxidants have been poorly explored. We investigated effects of the antioxidants lipoic acid (LA) and tempol in a model of atherosclerosis associated with elastocalcinosis. Male New Zealand white rabbits (2.5-3.0 kg) were fed regular chow (controls) or a 0.5% cholesterol (chol) diet+104 IU/day vitamin D2 (vitD) for 12 weeks, and assigned to treatment with water (vehicle, n=20), 0.12 mmol·kg-1·day-1 LA (n=11) or 0.1 mmol·kg-1·day-1 tempol (n=15). Chol+vitD-fed rabbits developed atherosclerotic plaques associated with expansive remodeling, elastic fiber disruption, medial calcification, and increased aortic stiffness. Histologically, LA prevented medial calcification by ∼60% and aortic stiffening by ∼60%. LA also preserved responsiveness to constrictor agents, while intima-media thickening was increased. In contrast to LA, tempol was associated with increased plaque collagen content, medial calcification and aortic stiffness, and produced differential changes in vasoactive responses in the chol+vitD group. Both LA and tempol prevented superoxide signals with chol+vitD. However, only LA prevented hydrogen peroxide-related signals with chol+vitD, while tempol enhanced them. These data suggest that LA, opposite to tempol, can minimize calcification and compliance loss in elastocalcionosis by inhibition of hydrogen peroxide generation.

Rescuing axons from degeneration does not affect retinal ganglion cell death

After a traumatic injury to the central nervous system, the distal stumps of axons undergo Wallerian degeneration (WD), an event that comprises cytoskeleton and myelin breakdown, astrocytic gliosis, and overexpression of proteins that inhibit axonal regrowth. By contrast, injured neuronal cell bodies show features characteristic of attempts to initiate the regenerative process of elongating their axons. The main molecular event that leads to WD is an increase in the intracellular calcium concentration, which activates calpains, calcium-dependent proteases that degrade cytoskeleton proteins. The aim of our study was to investigate whether preventing axonal degeneration would impact the survival of retinal ganglion cells (RGCs) after crushing the optic nerve. We observed that male Wistar rats (weighing 200-400 g; n=18) treated with an exogenous calpain inhibitor (20 mM) administered via direct application of the inhibitor embedded within the copolymer resin Evlax immediately following optic nerve crush showed a delay in the onset of WD. This delayed onset was characterized by a decrease in the number of degenerated fibers (P<0.05) and an increase in the number of preserved fibers (P<0.05) 4 days after injury. Additionally, most preserved fibers showed a normal G-ratio. These results indicated that calpain inhibition prevented the degeneration of optic nerve fibers, rescuing axons from the process of axonal degeneration. However, analysis of retinal ganglion cell survival demonstrated no difference between the calpain inhibitor- and vehicle-treated groups, suggesting that although the calpain inhibitor prevented axonal degeneration, it had no effect on RGC survival after optic nerve damage.

"Rakkaat poikaiset!". Simon ja Wilhelmina Janssonin perhekirjeet egodokumentteina (1858-1887)

Kustavilainen talonpoikaislaivuri Simon Jansson ja hänen vaimonsa Wilhelmina o.s. Widbom kävivät kolmenkymmenen vuoden ajan kirjeenvaihtoa kouluun ja yliopistoon lähetettyjen poikiensa Waldemar, Evald ja Emil Jahnssonin kanssa. Lähes 150 suomen- ja ruotsinkielistä kirjettä on säilynyt Suomalaisen Kirjallisuuden Seuran kirjallisuusarkistossa ja Turun maakunta-arkistossa. Lähiluvun kautta kirjeistä muodostuu yksityiskohtainen lähde saaristolaisperheen elämäntapaan, arkeen ja työhön sekä saaristoyhteisön sosiaalisen kanssakäymisen muotoihin. Ne kertovat myös ensimmäisen polven oppisivistyneistön synnystä ja niistä resursseista, joita hyödyntäen koulua käymättömät vanhemmat saattoivat kouluttaa lapsensa. Tutkimus liittyy suomalaisten 1800-luvun itseoppineiden kirjoittajien tekstien ja maaseudun kirjallistumisen tutkimukseen. Keskeinen käsite on egodokumentti, jolla tarkoitetaan kirjeitä ja muita tekstejä, joissa kirjoittaja kertoo itse omasta elämästään. Hollantilainen ja ranskalainen egodokumenttien tutkimus on pyrkinyt haastamaan uudenlaisten lähdeaineistojen kautta käsityksiä menneisyydestä sekä nostamaan esiin muun muassa yksilöllisen kokemuksen, kirjoittamisen kulttuurin ja dokumenttien materiaalisuuden. Janssonin perheen kirjeet poikkeavat monin tavoin 1800-luvun säätyläisten kirjeistä. Niiden funktio oli hyvin käytännöllinen ja arkinen, mutta ne olivat myös vanhempien keino tukea perheen yhteistä sosiaalisen nousun projektia. Kustavia koskevan tiheän uutisoinnin kautta ne pyrkivät pitämään kaupunkilaistuvat pojat osana vanhaa yhteisöään. Perheen isä vastasi suurelta osin kirjeenvaihdosta ja siihen liittyvästä huolenpidosta, mikä kertoo sukupuolittuneen työnjaon joustavuudesta saaristossa. Tutkimus osoittaa, ettei isän ammattiin perustuva yliopisto-opiskelijoiden tutkimus ole tavoittanut sitä naisten kautta välittyvää sosiaalista ja kulttuurista pääomaa, joka saattoi olla ratkaiseva perheiden kouluttaessa lapsiaan. Kirjeiden analyysi tarkentaa kuvaa perinteisen talonpoikaispurjehduksen sopeutumisesta vuosisadan loppupuolen uudistuksiin.

Modifications in the chemical compounds and sensorial attributes of Engraulis anchoita fillet during marinating process

Marinated fish are fish products preserved by the combined action of salt and organic acids. The objective of this work was to analyze the variations in the chemical compounds of anchovy fillets that give them sensorial characteristics during the marinating process of Engraulis anchoita. The protein content decreased slightly and the TVB-N level decreased significantly in both the brining and marinating stages. In the marinating stage an increase in the total free aminoacids was observed. The NBV level in the brining and marinating solutions increased during these stages due to the solubilization of the non-protein nitrogenous compounds and the degradation of some protein compounds.The decrease of the contents of protein and TVB-N, and the increase of the acidity and the free aminoacids content during the marinating process give the marinated fillets the characteristic texture and aroma.

Survey of aflatoxins in tomato products

Tomatoes are highly susceptible to fungi contamination in the field, during transportation, processing, and storage. Aspergillus flavus and Aspergillus parasiticus have been isolated from tomatoes and tomato products, and both fungi species can produce aflatoxin, mycotoxin with hepatotoxic, carcinogenic, teratogenic, and mutagenic effects on all animal species tested so far. In order to verify a possible aflatoxin contamination of tomato products commercialized in Brazil, 63 samples of tomato products (pulp, paste, purée, ketchup, dehydrated tomatoes, and dried tomatoes preserved in oil) produced in 5 Brazilian states and 1 imported sample (ketchup), totalizing 29 brands, were analyzed by thin layer chromatography. The analytical method showed an average recovery of 86% for all aflatoxins at two spiking levels. The limits of detection for the aflatoxins B1, B2, G1, and G2 varied with the type of the product ranging from 2 to 7 µg/kg. Aflatoxins were not detected in any evaluated sample indicating that they did not pose a risk to human health since there was no invasion of raw materials by toxigenic fungi or no conditions for toxin production.