Evidence for Different Nutrient Partitioning in Boran (Bos indicus) and Boran × Holstein Cows When Re‐allocated from Low to High or from High to Low Feeding Level

This study tested the hypothesis that purebred Boran (Bos indicus) cows and crossbreds of Boran and Holstein respond differently to long‐term changes of feeding level in nutrient partitioning to milk and body fat stores. A total of 27 cows of these two genotypes were subjected either to a low or a high feeding level from their first oestrus as heifers until birth of their third calf. Half of the cows of each genotype were then switched to the other feeding level during the third reproduction cycle. If at all, Boran cows responded to a change in the feeding level almost exclusively by a corresponding change in body weight but not milk yield. Crossbred cows kept continuously on the low feeding level had a lower milk yield than those continuously fed the high level, but lost similar amounts of body weight. In crossbred cows, changing the feeding level from high to low was accompanied by a mobilization of body reserves, whereas a change from low to high level resulted mostly in an increase in milk yield. Certain other genotype differences in metabolic response were obvious from differences in body composition and from the metabolic profile either reflected in blood (particularly insulin‐like growth factor I) or in adipose tissue (lipoprotein lipase). Reproductive performance differed between genotypes, with shorter lactations associated with earlier occurrences of the first oestrus in the Boran cows. Generally, feeding history appeared to have at least as much influence on energy partitioning as the actual feeding level. In conclusion, purebred Boran cows seem to react to long‐term food fluctuations mainly by mobilizing and restoring body fat reserves, whereas cows crossbred with Holstein tend to spend extra energy preferentially for milk production.     

Abomasal Cannulation in the Milk‐fed Calf Using a 7 mm Polyurethane Tube

The main objective of this study was to develop a simple and effective surgical technique for abomasal cannulation in neonatal calves. General anaesthesia was induced in 12, 3‐day‐old male dairy calves and a polyurethane cannula surgically implanted in the abomasal body (n = 12) and pyloric antrum (n = 6) through a right paracostal incision. Fifteen cannulae remained in situ from day 3 to 34 of life (mean: 29 days), and three cannulae were extruded 13–14 days after placement. Calves were clinically healthy and gained weight during the study. Cannulae were well tolerated by the calves and abomasal contents did not leak from the cannula sites. Necropsy examination revealed firm adhesions between the abomasum and parietal peritoneum at the cannula sites with no evidence of leakage or peritonitis. We conclude that surgical placement of polyurethane tubes designed for percutaneous endoscopic gastrostomy provided a useful method for cannulation of the abomasum of neonatal calves. The cannulation technique can be used for experimental studies, as well as for nutritional and fluid support of sick calves that cannot be managed by oral treatment.     

Activities of γ‐Glutamyltransferase,Alkaline Phosphatase and Aspartate‐Aminotransferase in Colostrum,Milk and Blood Plasma of Calves Fed First Colostrum at 0–2, 6–7, 12–13 and 24–25 h after Birth

Enzyme activities of γ‐glutamyltransferase (γ‐GT), alkaline phosphatase (AP) and aspartate‐aminotransferase (AST) were measured from birth to the age of 28 days in calves which were fed colostrum at 0–2, 6–7, 12–13, or 24–25 h after birth. Enzyme activities were also measured in colostrum (first to fifth milking) and in mature milk. Activities were highest in the first colostrum milking and decreased to the lowest activities in mature milk. Plasma γ‐GT activity transiently increased after first colostrum intake and was greater in calves fed first colostrum within less than 6–7 h than in those fed first colostrum later than 12 h after birth. Activity of γ‐GT reflected the absorption of colostral γ‐GT, which decreased with time after birth. The AP activity transiently increased after colostrum intake and was higher in calves fed colostrum within the first 12 h of life than in those fed later after birth. The transient rise of plasma AP activity also indicated absorption of colostral AP, although endogenous sources of AP could not be excluded. The activity of AST also transiently increased after colostrum intake but there was no association with time of first colostrum feeding, indicating that the rise of plasma AST activity was the consequence of enhanced endogenous production and was independent of colostrum intake. In conclusion, there are different causes leading to postnatal changes in enzyme activities.     

Plasma Amino Acid Pattern during the First Month of Life in Calves Fed the First Colostrum at 0–2 h or at 24–25 h after Birth

Calves are born with a mostly inadequate essential amino acid (EAA) status. Studies were designed to test the hypothesis that delaying the intake of the first colostrum for 24 h, besides its early effects, also has late effects on plasma free amino acid levels and on the protein status. There were marked and rapid elevations (within 2 h) of plasma levels of various amino acids, and especially of EAA, after the intake of the first colostrum, whereas changes after the intake of mature milk on day 28 of life were mostly absent or concentrations even decreased. The EAA and non‐essential amino acid (NEAA) status was rapidly normalized after intake of the first colostrum, but normal plasma levels of some amino acids were also reached during the first 24 h of life even when the first meal was withheld. Delaying colostrum intake had only transient effects on EAA and NEAA (except hydroxyproline), in contrast to its effects on plasma immunoglobulin G and total protein levels.     

Testosterone and obesity in men under the age of 40 years

The study assessed anthropometric and laboratory variables, in particular testosterone (T) in a group of obese men of <40 years. Of 60 men with a body mass index (BMI) of >27 kg m^?2, 34 met the criteria of the metabolic syndrome (MS). Twenty men <40 years (with a BMI <25 kg m^?2) were studied for comparison. It was found that with increasing BMI, levels of serum leptin, triglycerides, insulin, the ratio high‐density lipoprotein (HDL) cholesterol/low‐density liporotein (LDL) cholesterol, the waist circumference (WC), the area of visceral fat and systolic/diastolic blood pressure were higher, whereas insulin sensitivity (HOMA) and serum T were lower. Obesity (BMI 27–30 kg m^?2) was associated with a decline in plasma T, but not with a decline in plasma sex hormone‐binding globulin (SHBG). The latter was the case in more severe obesity (>30 kg m^?2) qualifying as MS. In patients with MS, 58% variability of T levels could be predicted by combination of independent factors – SHBG, ratio LDL/HDL, insulin and leptin. On the other hand, in men with MS, 80% variance of concentrations of SHBG were predicted by triglycerides, HDL, glucose, leptin and surface of visceral adipose tissue. It is concluded that plasma T is significantly correlated with a number of features of the MS and, therefore, plasma T could serve as a marker of the MS.     

Evaluation of the Interferon‐γ Assay on Blood Collected at Exsanguination of Cattle Under Field Conditions for Surveillance of Bovine Tuberculosis

Development of point of concentration (POC) surveillance strategies for bovine tuberculosis (bTB) would facilitate global efforts to eradicate bTB. The interferon‐gamma (IFNγ) assay can detect IFNγ responses to Mycobacterium bovis in blood collected at commencement of exsanguination (COE) of experimentally challenged cattle but has not been evaluated under field conditions. The current study was aimed at determining (i) whether blood collected at COE of cattle at slaughter, under field conditions, is practical to obtain and useful for identifying cattle as IFNγ positive for bTB, (ii) whether the results of the IFNγ assay obtained at COE reliably compare with results obtained from live animals in the field, and (iii) whether the identified animal(s) originated from bTB‐infected or bTB‐exposed herds. Cattle from three risk groups were used: the highest risk group consisted of 49 cattle from 3 bTB‐infected herds; the medium risk group consisted of 24 cattle from a potentially exposed herd; and the lowest risk group consisted of 60 cattle from herds with no known history of bTB exposure. The IFNγ assay was performed on blood collected both before stunning and at COE of cattle at slaughter. An enhanced slaughter inspection for gross lesions consistent with bTB was performed on all cattle. In addition, lymph nodes were cultured for M. bovis for cattle that tested positive for bTB via the IFNγ assay and for most cattle that tested negative for bTB. Cattle, both with and without lesions consistent with bTB, were identified as positive for bTB by the IFNγ assay using blood collected at COE, but none of the positive cattle originated from the lowest risk group. The current study demonstrates that blood collected at COE of cattle is both a practical and moderately reliable sample for accessing bTB infection using the IFNγ assay.     

Prevalence and risk factors associated with chronic kidney disease in adults over 40 years: A population study from Central China

Aim: Chronic kidney disease (CKD) poses a serious public health problem worldwide. Population‐based studies determining the prevalence of this disease in China have been limited in several large developed cities. In the present study, a population‐based screening study in Henan, a representative province in Central China, was conducted in order to quantify the prevalence of CKD and identify the associated risk factors for this disease in a population of developing areas of China. Methods: Residents (n = 4156) over 40 years old in four major cities of Henan Province were interviewed and their albuminuria, reduced renal function, haematuria and blood pressure were measured. Associations between age, components of metabolism syndrome and indicators of CKD were examined. Results: Among these subjects, the prevalence rates of albuminuria, haematuria and reduced renal function were 4.51%, 6.28% and 1.53%, respectively. Approximately 10.49% of the subjects had at least one indicator of kidney damage. The awareness rate of this disease in subjects with CKD was only 9.50%. Hypertension, diabetes and hyperuricaemia were three independent risk factors for CKD. Conclusion: The high prevalence and low awareness of CKD in the studied population suggest that CKD is a severe public health problem in Central China. Effectively preventive and therapeutic interventions are needed.     

The effect of a 3 : 1 volume mixture of propofol 1% and thiopental 2.5% in reducing the pain on injection of propofol in children1

Background: In this prospective, randomized, double‐blind, controlled trial, our primary objective was to assess the effect of a 3 : 1 mixture of propofol and thiopental in reducing pain on injection in children. Our hypothesis was that a 3 : 1 mixture of propofol and thiopental (treatment) would reduce the incidence of pain on injection to 20% compared to the expected incidence of 40% in the control group of an 11 : 1 mixture of propofol and 2% lidocaine. Methods: Study subjects were patients 12–17 years old who were scheduled to undergo surgery and general anesthesia. Pain was assessed by a single‐blinded observer present in the operating room. The major statistical method used in the analysis was multiple logistic regression. Results: Among the 164 children analyzed, 96 patients (58.5%) were male. The average age was 14.3 (sd = 1.65). The incidence of pain in the control group was 32.1% (26/81), compared to 25.3% (21/83) in the treatment group. The logistic regression analysis showed that there was not sufficient evidence that the treatment group was better than control group in reducing pain (P = 0.24). There were no significant differences in postoperative recovery time, nausea, vomiting, or blood pressure between the two groups (all P values >0.10). Conclusion: There was not sufficient evidence to show that a 3 : 1 mixture of propofol and thiopental was better than an 11 : 1 volume admixture of propofol and lidocaine in reducing the incidence of pain on injection to 20%.     

40 years of heart transplantation and the DFG‐Transregio Research Group Xenotransplantation

Today, organ transplantation represents a well‐established and effective therapy of terminal organ failure revealing high actuarial survival rates. Unfortunately, the enormous potential of organ transplantation cannot be tapped due to the significant gap between organ demand and organ donation. Current statistics of the International Society of Heart and Lung Transplantation prove a continuity of depressed numbers of transplantations performed per year since the late nineties. To counteract the persisting severe shortage of human organs in Germany and worldwide suboptimal donor organs and/or organs from older donors were accepted. Both the acceptance of inferior organs and the implementation of the Transplantation Law (in Germany in 1997) could not answer this problem. Increasing the donor rates emerge difficult to achieve and will ultimately result in numbers which are not sufficient. The improvement of transplant results by e.g. a less nephrotoxic immunosuppression, or the generating of hyporeactivity or even tolerance is an additional aim important to achieve. Alternative techniques to answer the tremendous organ shortage might be the differentiation of embryonic stem cells or the reprogramming of adult stem cells as a virtually unlimited source for cell replacement to treat degenerative diseases or traumatic tissue injury. Yet, disadvantages such as ethical issues and the generation of tumorigenic cells should not be underestimated. A cellular therapy by the injection of undifferentiated bone marrow (CD133⁺ stem/progenitor) cells into the myocardium in combination with or without aortocoronary surgery for chronic ischemic heart disease as well as cells from the amniotic fluid (Wharton's jelly) might also represent possible future solutions to the organ deficit but still are far from a functional substitution of the human heart. Until now there is no in‐all implantable mechanical heart assist device which is able to completely and permanently replace the human organ and provide a quality of life comparable to that after allotransplantation. In contrast, xenotransplantation, using porcine organs for human transplantation, offers a potential solution to the world‐wide lack of donor organs. The advantages of xenotransplantation are an unlimited disposability of donor organs, an elective transplantation with a subsequent reduction of ischemic time and the possibility of a pre‐operative start of the immunosuppressive therapy of the recipient. Harmful effects of the brain death of the donor to the donor organ could be excluded. Finally, genetic modifications of compatible xenografts could be made. Substantial progress of the research in the field of xenotransplantation has been possible thanks to the introduction of organs from genetically engineered pigs transgenic for human complement regulatory proteins [e.g. human decay accelerating factor (hDAF/hCD55), human membrane cofactor (hMCP/hCD46), and human membrane inhibitor of reactive lysis (hMIRL/hCD59)]. Using an effective and persistent depletion of preformed cytotoxic anti‐Galα(1,3)Gal antibodies (IgM and IgG) by a Galα(1,3)Gal therapeutic (e.g. GAS914, TPC) in combination with these transgenic pigs hyperacute rejection can be avoided successfully. During the early phase after transplant acute vascular rejection triggered by induced anti‐Galα(1,3)Gal antibodies can be controlled. Several groups developed pigs which lack the Galα(1,3)Gal xenoantigen. Studies on xenotransplantations performed with homozygous alpha(1,3)‐galactosyltransferase gene knockout pigs demonstrated that these modified pig organs offer some progress in terms of graft survival. Thus, the major xenoantigen Galα(1,3)Gal is no longer an unsurmountable immunological barrier preventing transplantation of pig organs into humans. Acute vascular rejection, however, remains as a major hurdle to clinical application of xenotransplantation due to cytotoxic anti‐pig antibodies of other specificity than Galα(1,3)Gal. Furthermore, humoral factors are not the only players in xenograft rejection. Primate anti‐pig cellular immunity is defined by multifocal lymphocytic infiltrates, with morphologic evidence of direct tissue damage. Pre‐requisites for the clinical use of xenotransplantation are PERV‐C (porcine endogenous virus C) free animals using a PERV knock down (si‐RNA) technique. Multitransgenic αGalT‐KO [alpha(1,3)‐galactosyltransferase knockout] pigs additionally expressing human complement regulator proteins, and human anticoagulants (e.g. human thrombomodulin) are necessary to reliably prevent not only hyperacute rejection as the first immunological barrier, but also acute vascular rejection at its beginning, when serum cytotoxicity to the pig heart appears to be predominantly Galα(1,3)Gal‐specific. Further co‐stimulation blockade (e.g. PD‐1L, CTLA‐4‐Ig), HLA‐E [protection against human NK (natural killer)‐cells], or haemeoxygenase‐1 (defense against disseminated intravascular coagulation) will help to suppress acute vascular and acute cellular xenograft rejection. Special pathogen free (SPF) units and breeding conditions of pig organ donors limit the risk of microbial contamination by most pathogens liable to be transmitted from a pig graft to a human recipient. Our DFG‐(German Research Council) Transregio Research Group Xenotransplantation assembles an interdisciplinary group of leading German laboratories incl. biotechnologists, immunologists, virologists, and surgeons with vast experimental expertises in the field of experimental and clinical allotransplantation and experimental xenotransplantation. The first clinical goal of xenotransplantation is xenogeneic tissue transplantation such as the transplantation of porcine islet cells (αGalT‐KO (?), CTLA‐4‐Ig expression) in diabetic patients with hypoglycemic attacks as well as porcine cornea, porcine cardiomyocytes and porcine heart valves, possibly porcine bones and teeth (?). Thereafter, xenogeneic organ transplantation starting with the more promising use of kidneys and hearts is the definitive clinical goal. In summary, clinical heart transplantation represents an accepted method of end‐stage heart failure with an outdated “standard immunosuppression” and the need of an individualized immunosuppression adjusted to the specific needs of the individual patient. The organ shortage remains the main obstacle of the heart transplantation, and other organ transplantation, respectively. In the near future, xenotransplantation will be possible!     

Haemodynamic effects of −75 mmHg negative pressure therapy in a porcine sternotomy wound model

Previous research has shown ?125 mmHg to be the optimal negative pressure for creating an environment that promotes wound healing, and this has therefore been adopted as a standard pressure for patients with deep sternal wound infection. However, it has not yet been clearly shown that ?125 mmHg is the optimal pressure from a haemodynamic point of view. Furthermore, there have been reports of cardiac rupture during ?125 mmHg negative pressure therapy. We therefore studied the effects of a lower pressure: ?75 mmHg. Twelve pigs were used. After median sternotomy, sealed negative pressure therapy of ?75 mmHg was applied. Baseline measurements were made and continuous recording of the cardiac output, end‐tidal CO₂ production, mean arterial pressure, mean pulmonary pressure (pulmonary artery pressure), systemic vascular resistance, pulmonary vascular resistance, left atrial pressure and central venous pressure was started. Six pigs served as controls. No statistically significant difference was observed in any of the haemodynamic parameters studied, compared with the controls. The present study shows that, with a suitable foam application technique, ?75 mmHg can be applied without compromising the central haemodynamics.