Untersuchungen zur Stabilisierung der frühen postnatalen Adaptationsvorgänge bei Kälbern in Mutterkuhhaltung - ein Beitrag zur Charakterisierung postnataler Anpassungsreaktionen

Ziel dieser Arbeit war es, die sensible Phase der ersten und frühen zweiten Adaptationsphase, von der Geburt bis zur 72. Lebensstunde, bei Kälbern fleischbetonter Rassen in einem geschlossenen Mutterkuhbestand zu untersuchen, um daraus folgend einen Beitrag zur Erstellung von nicht parametrischen Referenzbereichen für klinische und labordiagnostische Parameter für diese Zeitspanne zu leisten. Korrelationen zwischen klinischen und labordiagnostischen Parametern sollten aufgedeckt werden, um so klinisch relevante Beziehungen herstellen zu können Eine Einschätzung der Vitalität anhand leicht zu erhebender ethologischer Befunde, wie erstes Kopfheben post natum, erstes sicheres Stehen und erste Kolostrumaufnahme wurde durchgeführt. Als Probanden standen insgesamt 115 mature Kälber verschiedener Rassen aus einem geschlossenen Mutterkuhbestand zur Verfügung. Die Untersuchung erstreckte sich von der Geburt bis zu 72 Stunden p. n.. Folgende 20 Parameter kamen dabei zur Auswertung: pH, Base Excess, Kohlendioxidpartialdruck, Hä­¡tokrit, Gesamtprotein, Glukose, Triglyzeride, Cholesterin, Harnstoff, Kreatinin, Natrium, Kalium, Chlorid, Magnesium, AST, ALT, AP, GGT, GLDH und CK. Die statistische Auswertung der Ergebnisse wurde unter Berücksichtigung der Faktoren Alter, Rasse, Geschlecht und Geburtsart der Kälber sowie Geburtsziffer des Muttertieres vorgenommen. Die einzelnen Messgrössen bis auf das Plasmachlorid wurden über den Untersuchungszeitraum hochsignifikant (p < 0,001) durch das Alter beeinflusst. Einflí²í³¥ der Rasse zeigten sich im Verlauf des Blut-pH-Wertes (p <= 0,01), des Base Excess (p <= 0,05) sowie der Enzyme ALT (p <= 0,05) und GLDH (p <= 0,05). Das erste sichere Stehen post natum wurde schwach signifikant durch das Geschlecht (p <= 0,05) beeinflusst. Die Parameter pH-Wert (p <= 0,05) und Kohlendioxidpartialdruck (p <= 0,01) im venösen Blut sowie die Blutglukose (p <= 0,01) zeigten bis zum dritten Lebenstag ebenfalls Einflüsse durch das Geschlecht der Kälber. Die Geburtsart übte einen signifikanten Einfluss auf die ethologischen Parameter des ersten Stehens (p <= 0,01) und des ersten Saugens post natum (p <= 0,01) aus, die Einstufung nach APGAR wurde sogar hoch signifikant (p <= 0,001) durch die Geburtsart beeinflusst. Labordiagnostisch konnte ein signifikanter Einfluss auf die CK-Aktivität (p <= 0,01) ermittelt werden. pH-Wert, Kaliumkonzentration und AST-Aktivität erfuhren schwach signifikante (p <= 0,05) Beeinflussungen durch die Art der Geburt. Die Parität der Muttertiere, beeinflusste die Geburtsart signifikant (p <= 0,01). Ebenso wiesen die Serumspiegel des Gesamtproteins (p <= 0,05), von Harnstoff (p <= 0,01), Kalium (p <= 0,05), ALT (p <= 0,05) und GLDH (p <= 0,05) Einflüsse der die Geburtsziffer auf. Im Verlauf der AP-Aktivitäten zeigten sich hoch signifikante Wechselwirkungen (p <= 0,001) mit den verschiedenen Rassen. Das Geschlecht der Kälber wies ebenso hoch signifikante Wechselwirkungen (p <= 0,001) zur GLDH-Aktivität auf. Wechselwirkungen der Geburtsart und der Zeit waren bei den Messgrössen pH-Wert (p <= 0,001), Kohlendioxidpartialdruck (p <= 0,01), Base Excess (p <= 0,001), Hämatokrit (p <= 0,001), Harnstoff (p <= 0,05) und AST-Aktivität (p <= 0,05) statistisch nachweisbar. Auf die Parameter Harnstoff (p <= 0,001), Natrium (p <= 0,05), Kalium (p <= 0,05), Chlorid (p <= 0,05) und ALT-Aktivität (p <= 0,05) waren Wechselwirkungen der Geburtsziffer der Muttertiere von der Geburt bis zur 72. Lebensstunde darstellbar. Die Körpertemperatur der Kälber korrelierte unmittelbar nach der Geburt signifikant (p <= 0,01) mit dem Blut-pH-Wert (r = -0,283) und dem Kohlendioxidpartialdruck (r = +0,284). Zum Base Excess bestand postnatal eine schwach signifikante (p <= 0,05) Korrelation (r = -0,193). Die Blutglukosewerte korrelierten unmittelbar post natum schwach signifikant (p <= 0,05) mit dem Blut-pH (r = -0,207), dem Kohlendioxidpartialdruck (r = +0,089) und dem Base Excess (r = 0,210). Das erste Kopfheben post natum stand in hoch signifikantem (p <= 0,001) Zusammenhang mit der Vitalitätseinschätzung nach APGAR. Das erste Stehen zeigte einen signifikante (p <= 0,01) und der Zeitpunkt der ersten Kolostrumaufnahme noch einen schwach signifikanten (p <= 0,05) Zusammenhang. Zur exakten Einschätzung der labordiagnostisch ermittelten Blutwerte bei neugeborenen Kälbern ist eine vom genauen Alter abhängige Erstellung von Referenzbereichen unter Berücksichtigung nicht parametrischer Referenzbereiche notwendig.The aim of the present study was to illustrate the sensitive time of the first and the early second adaptation period from birth to the 72. hour of life in different races of beef cattle in one herd. Furthermore non parametric reference values for clinical and laboratory diagnostic parameters for this period of adaptation were described. Another aim was to find correlations between clinical and laboratory parameters to show relations of clinical relevance. Ethological findings such as: first raising of the head post natum, first firm standing and colostrum intake were evaluated. For tests, a total of 115 mature calves of different races out of a close suckler cow management system herd was available. The evaluation was made from immediately after birth to 72 hours p. n.. The following 20 parameters were evaluated: pH, base excess, carbondioxide partial pressure, hematocrit, total protein, glucose, triglyceride, cholesterol, uric acid, creatinin, sodium, calium, potassium, chloride, magnesium, AST, ALT, AP, GGT, GLDH and CK. When doing the statistical evaluation of the results factors such as: age, race, sex, kind of birth of the calves as well as the number of births given by the mother cow were considered. The development of the single values over the time period of the research was highly influenced by the age (p <= 0.001). Influence of the race was found during the course of the blood-pH-value (p <= 0.01), of the base excess (p <= 0.05) and also of the enzymes ALT (p <= 0.05) and GLDH (p <= 0.05). The time of first firm standing post natum as a qualifying factor was only weak significantly (p <= 0.05) influenced by the sex. The parameter blood-pH (p <= 0.05), blood glycose (p <= 0.01) and carbondioxide partial pressure (p <= 0.01) also proved influence of the sex of the calves during the first 3 days after birth. The kind of birth had a significant influence on the ethological parameter of the first standing (p <= 0.01) and the first suckling post natum (p <= 0.01). When judging according to APGAR the correlation was even highly significant (p <= 0.001). In the laboratory diagnostics a significant influence on the CK-activity (p <= 0.01) could be found. pH-value, potassium concentration and AST-activity were weak significantly influenced (p <= 0.05) by the kind of birth. The kind of birth was significantly influenced (p <= 0.01) by the fact how often a mother cow already had given birth to calves. The serum level of the total protein (p <= 0.05), of the uric acid (p <= 0.01), potassium (p <=0.05), ALT (p <= 0.05) and GLDH (p <= 0.05) also showed their correlation to the number of birth. During the course of the AP activities of the different races significant interactions became obvious (p <= 0.001). The sex of the calves also showed highly significant interactions (p <= 0.001) towards the GLDH activity. Interactions of the kind and time of birth could also statistically be proven for the parameters: pH value (p <= 0.001), carbondioxide partial pressure (p <= 0.01), base excess (p <= 0.001), hematocrit (p <= 0.001), uric acid (p <= 0.05) and AST activity (p <= 0.05). For the parameters uric acid (p <= 0.001), sodium (p <= 0.05), potassium (p <= 0.05), chloride (p <= 0.05) and AST activity (p <= 0.05), an interaction could be found to the number of births given by the mother cow from the date of birth till the 72nd hour after birth. Correlation was discovered between body temprature and blood glycose to pH, carbondioxide partial pressure and base excess. The body temperature of the calves correlated after birth directly and significantly (p <= 0.01) with the blood-pH-value (r = -0.283) and the carbondioxide partial pressure (r = +0.284). There existed a slightly significant (p <= 0.05) correlation (r = -0.193) to the base excess. The blood glycose values correlated directly post natum slightly significantly (p <= 0.05) with the blood-pH (r = -0.207) with the carbondioxide partial pressure (r = +0.089) and with the base excess (r = 0.210). The first raising of the head post natum was in a highly significant connection (p <= 0.001) with the judgement of the vitality by APGAR. The first standing up showed a significant (p <= 0.01) and the time of first intake of cholostrum still a weak significant (p <=0.05) correlation. For the exact evaluation of the blood values derived from laboratory diagnostics for newly born calves, a table with values referring to the exact age and also considering the non-parameter values must be created

Association of constipation with increased risk of hypertension and cardiovascular events in elderly Australian patients

Abstract The association between constipation and cardiovascular risk is unclear. This population-level matched cohort study compared the association of constipation with hypertension and incident cardiovascular events in 541,172 hospitalized patients aged ≥ 60 years. For each constipation admission, one exact age-matched non-constipated admission was randomly selected from all hospitalizations within 2 weeks to form the comparison cohort. The association of constipation with hypertension and cardiovascular events (myocardial infarction, angina, stroke and transient ischemic attack) were analysed using a series of binary logistic regressions adjusting for age, sex, cardiovascular risk factors, gastrointestinal disorders and sociological factors. Patients with constipation had a higher multivariate-adjusted risk for hypertension (odds ratio [OR], 1.96; 95% confidence interval [CI] 1.94–1.99; P < 0.001). Compared to patients with neither constipation nor hypertension, there was a higher multivariate-adjusted risk for cardiovascular events in patients with constipation alone (OR, 1.58; 95% CI 1.55–1.61; P < 0.001) or hypertension alone (OR, 6.12; 95% CI 5.99–6.26; P < 0.001). In patients with both constipation and hypertension, the risk for all cardiovascular events appeared to be additive (OR, 6.53; 95% CI 6.40–6.66; P < 0.001). In conclusion, among hospital patients aged 60 years or older, constipation is linked to an increased risk of hypertension and cardiovascular events. These findings suggest that interventions to address constipation may reduce cardiovascular risk in elderly patients

Augmented superoxide production by Nox2-containing NADPH oxidase causes cerebral artery dysfunction during hypercholesterolemia

Background and Purpose— We tested the hypothesis that elevated superoxide production by Nox2-NADPH oxidase occurs in cerebral arteries during hypercholesterolemia and causes decreased nitric oxide function. Methods— Wild-type (WT), apolipoprotein E-deficient (ApoE−/−) and Nox2−/−/ApoE−/− mice were fed a high-fat diet for 7 to 14 weeks. Basal superoxide production by cerebral arteries was measured using L-012 (100 μmol/L)-enhanced chemiluminescence. Nitric oxide function was assessed in isolated middle cerebral arteries through the constrictor response to Nω-nitro-L-arginine methyl ester (L-NAME; 100 μmol/L). Western blotting was used to measure protein expression of Nox2, p47phox, endothelial nitric oxide synthase, and superoxide dismutases (1–3). Results— Morphology of cerebral arteries was similar in WT and ApoE−/− mice. In ApoE−/−, but not Nox2−/−/ApoE−/− mice, superoxide production by cerebral arteries was approximately 50% greater than in WT mice (P&lt;0.05). Moreover, the magnitude of L-NAME-induced contractions of isolated middle cerebral arteries from ApoE−/− mice was &lt;50% of that in WT mice (P&lt;0.05), whereas in Nox2−/−/ApoE−/− mice, the contractile response was comparable to WT responses. In the presence of the superoxide scavenger, tempol (1 mmol/L), L-NAME-induced contractions of middle cerebral arteries were similar between WT and ApoE−/− mice. Expression of p47phox was approximately 2-fold higher in ApoE−/− versus WT mice, whereas Nox2, endothelial nitric oxide synthase, and superoxide dismutase isoforms were unchanged. Conclusions— Elevated superoxide production and reduced basal nitric oxide-mediated relaxation occur in cerebral arteries of hypercholesterolemic mice even in the absence of lesions. These changes appear to be exclusively due to increased activity of Nox2-NADPH oxidase, possibly through increased expression of its regulatory subunit p47phox

NADPH-induced contractions of mouse aorta do not involve NADPH Oxidase: A role for P2X receptors

Reactive oxygen species elicit vascular effects ranging from acute dilatation because of hydrogen peroxide-mediated opening of K+ channels to contraction arising from superoxide-dependent inactivation of endothelium-derived nitric oxide. Given that NADPH oxidases are major sources of superoxide in the vascular wall, this study examined the effects of exogenous NADPH, a substrate of these enzymes, on superoxide generation and isometric tone in mouse isolated aortic rings. NADPH caused concentration-dependent increases in superoxide generation (measured by lucigenin-enhanced chemiluminescence) and vascular tone (isometric tension recordings). However, surprisingly, whereas oxidized NADP+ was unable to support superoxide production, it was equally as effective as reduced NADPH at stimulating vasocontraction. In addition, an NADPH oxidase inhibitor, diphenyleneiodonium, markedly attenuated NADPH-induced superoxide production, yet had no effect on vasocontractions to NADPH. In contrast, a broad specificity P2X receptor antagonist, pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid, as well as the P2X1 selective antagonist, NF023, markedly attenuated both endothelium-dependent and -independent vasocontractions to NADPH, as did the P2X-desensitizing agent α,β-methylene-ATP. Importantly, α,β-methylene-ATP had no effect on superoxide production induced by NADPH. In conclusion, these findings suggest little role for NADPH oxidase-derived superoxide in the contractile effects of NADPH in the mouse aorta. Rather, NADPH seems to act as an agonist at two distinct P2X receptor populations; one located on the endothelium and the other on smooth muscle layer, both of which ultimately lead to contraction

Major cardiovascular events in males.

<p>DS = Down syndrome.</p><p>Any cerebrovascular event includes stroke (ischemic, hemorrhagic or unspecified) or transient ischemic attack.</p><p>Any coronary event includes myocardial infarction or angina.</p><p>* P<0.05</p><p>** P<0.01</p><p>*** P<0.001 (McNemar test)—for comparing proportions between DS and non-DS groups</p><p>(Data are n [%] patients unless indicated otherwise).</p

Sample characteristics.

<p>DS = Down syndrome.</p><p>† presence of either of congenital heart disease, cardiac arrhythmia or pulmonary hypertension</p><p>†† presence of any of hypertension, diabetes mellitus, sleep apnea, smoking</p><p>††† presence of any of congenital heart disease, cardiac arrhythmia, pulmonary hypertension, hypertension, diabetes mellitus, sleep apnea, smoking or Moyamoya disease</p><p>* P<0.05</p><p>** P<0.01</p><p>*** P<0.001 (McNemar test)–for comparing proportions between DS and non-DS groups</p><p>(Data are n [%] patients unless indicated otherwise).</p

Major cardiovascular events in females.

<p>DS = Down syndrome</p><p>Any cerebrovascular event includes stroke (ischemic, hemorrhagic or unspecified) or transient ischemic attack.</p><p>Any coronary event includes myocardial infarction or angina.</p><p>* P<0.05</p><p>** P<0.01</p><p>*** P<0.001 (McNemar test)—for comparing proportions between DS and non-DS groups</p><p>(Data are n [%] patients unless indicated otherwise).</p

Risk of cardiovascular events in patients with Down Syndrome.

<p>DS = Down Syndrome; MI = myocardial infarction; TIA = transient ischemic attack.</p><p>Cerebrovascular events include stroke (ischemic, hemorrhagic or unspecified) or transient ischemic attack.</p><p>Coronary events include myocardial infarction or angina.</p><p>Model 1: adjusted for sex</p><p>Model 2: adjusted for sex and overall cardiovascular risk</p><p>(Overall cardiovascular risk is represented by a variable that includes the presence of any of congenital heart disease, cardiac arrhythmia, pulmonary hypertension, hypertension, diabetes mellitus, sleep apnea, smoking or Moyamoya disease)</p><p>* P<0.05</p><p>** P<0.01</p><p>*** P<0.001</p><p>(Data are n [%] patients unless otherwise indicated).</p