Mapping of quantitative trait loci for clinical-chemical traits in swine.

Clinical-chemical traits are diagnostic parameters essential for characterization of health and disease in veterinary practice. The traits show significant variability and are under genetic control, but little is known about the fundamental genetic architecture of this variability, especially in swine. We have identified QTL for alkaline phosphatase (ALP), lactate (LAC), bilirubin (BIL), creatinine (CRE) and ionized sodium (Na(+)), potassium (K(+)) and calcium (Ca(++)) from the serum of 139 F(2) pigs from a Meishan/Pietrain family before and after challenge with Sarcocystis miescheriana, a protozoan parasite of muscle. After infection, the pigs passed through three stages representing acute disease, subclinical disease and chronic disease. Forty-two QTL influencing clinical-chemical traits during these different stages were identified on 15 chromosomes. Eleven of the QTL were significant on a genome-wide level; 31 QTL were chromosome-wide significant. QTL showed specific health/disease patterns with respect to the baseline values of the traits as well as the values obtained through the different stages of disease. QTL influencing different traits at different times were found primarily on chromosomes 1, 3, 7 and 14. The most prominent QTL for the investigated clinical-chemical traits mapped to SSC3 and 7. Baseline traits of ALP, LAC, BIL, Ca(++) and K(+) were influenced by QTL regions on SSC3, 6, 7, 8 and 13. Single QTL explained up to 21.7% of F(2) phenotypic variance. Our analysis confirms that variation of clinical-chemical traits is associated with multiple chromosomal regions.

Heritabilities and quantitative trait loci for blood gases and blood pH in swine.

Maintaining pH and blood gases in a narrow range is essential to sustain normal biochemical reactions. Decreased oxygenation, poor tissue perfusion, disturbance to CO(2) expiration, and shortage of HCO(3)(-) can lead to metabolic acidosis. This is a common situation in swine, and originates from a broad range of medical conditions. pH and blood gases appear to be under genetic control, and populations with physiological traits closer to the pathological thresholds may be more susceptible to developing pathological conditions. However, little is known about the genetic basis of such traits. We have therefore estimated phenotypic and genetic variability and identified quantitative trait loci (QTL) for pH and blood gases in blood samples from 139 F(2) pigs from the Meishan/Pietrain family. Samples were taken before and after challenge with Sarcocystis miescheriana, a protozoan parasite of muscle. Twenty-seven QTL influencing pH and blood gases were identified on nine chromosomes. Five of the QTL were significant on a genome-wide level; 22 QTL were significant on a chromosome-wide level. QTL for pH-associated traits have been mapped to SSC3, 18 and X. QTL associated with CO(2) have been detected on SSC6, 7, 8 and 9, and QTL associated with O(2) on SSC2 and SSC8. QTL showed specific health/disease patterns that were related to the physiological state of the pigs from day 0, to acute disease (day 14), convalescence (day 28) and chronic disease (day 42). The results demonstrate that pH and blood gases are influenced by multiple chromosomal areas, each with relatively small effects.

Sulfhydryl oxidation: a potential strategy to achieve neuroprotection during severe hypoxia?

Previously we reported that sulfhydryl (SH) modulation affects the susceptibility of rat hippocampal slices to severe hypoxia. SH-oxidation by DTNB (5,5'-dithiobis 2-nitrobenzoic acid) or H2O2 postponed the onset of hypoxia-induced spreading depression (HSD), thereby delaying the loss of neuronal function, whereas SH-reduction by DTT (1,4-dithio-dl-threitol) hastened HSD onset. To judge the neuroprotective merit that might arise from a postponement of HSD by oxidants, we have extended our earlier observations by multiparametric recordings and screened for changes in the extracellular K+ accumulation, HSD propagation velocity, and its maximum spread. As parameters for neuronal network function, the failure of synapses during hypoxia and their posthypoxic recovery were analyzed. DTNB (2 mM) or H2O2 (5 mM) postponed HSD but did not attenuate the rise in extracellular K+ concentration ([K+](o)), HSD propagation velocity or its maximum spread. H2O2 slightly postponed the synaptic failure during hypoxia; the posthypoxic recovery of synapses was, however, incomplete. DTNB slowed the synaptic recovery upon reoxygenation. DTT (2 mM) hastened HSD onset, but HSD propagation velocity and tissue invasion were not affected. Upon reoxygenation, however, normalization of [K+](o) was disturbed and synaptic recovery failed. Therefore, SH-reducing conditions at the onset of HSD proved to be devastating for the hippocampal network. In conclusion, the only merit of DTNB or H2O2 treatment is a delayed HSD onset, i.e. some extra time before neuronal function is lost during severe hypoxia. Attenuation of the severe changes during HSD or an improved outcome was not observed. Nevertheless, combination of SH-oxidants with established neuroprotectants might be a potential therapeutic approach.

Quantitative trait loci for white blood cell numbers in swine.

Differential white blood cell counts are essential diagnostic parameters in veterinary practice but knowledge on the genetic architecture controlling variability of leucocyte numbers and relationships is sparse, especially in swine. Total leucocyte numbers (Leu) and the differential leucocyte counts, i.e. the fractions of lymphocytes (Lym), polymorphonuclear leucocytes [neutrophils (Neu), eosinophils (Eos) and basophils (Bas)] and monocytes (Mon) were measured in 139 F(2) pigs from a Meishan/Pietrain family, before and after challenge with the protozoan pathogen Sarcocystis miescheriana for genome-wide quantitative trait loci (QTL) analysis. After infection, the pigs passed through three stages representing acute disease, reconvalescence and chronic disease. Nine genome-wide significant and 29 putative, single QTL controlling leucocyte traits were identified on 15 chromosomes. Because leucocyte traits varied with health and disease status, QTL influencing the leucocyte phenotypes showed specific health/disease patterns. Regions on SSC1, 8 and 12 contained QTL for baseline leucocyte traits. Other QTL regions reached control on leucocyte traits only at distinct stages of the disease model. Two-thirds of the QTL have not been described before. Single QTL explained up to 19% of the phenotypic variance in the F(2) animals. Related traits were partly under common genetic influence. Our analysis confirms that leucocyte trait variation is associated with multiple chromosomal regions.

[Phenotypic and genetic variation in hematological traits of Pietrain-Meishan-F2 crossbred pigs]. / Phänotypische und genetische Variation hämatologischer Merkmale bei Pietrain- Meishan-F2-Kreuzungsschweinen.

Hematological traits are essential parameters for veterinary practice to quantify health status of individuals and herds. A major problem with the interpretation of hematological values is their pronounced variability that is to a great extend caused by non-systematic factors. Differences in breeds and populations are providing evidence for different genotypes in this regard, although there is no information available in swine about the nature and shares of participating genes. Goal of the present paper was to evaluate the additive-genetic share of total variability of traits of the red and white blood cell count. The results are based on 139 F2-pigs of a Pietrain-Meishan-family. Medium to high heritabilities have been estimated for the numbers of neutrophiles, the mean corpuscular hemoglobin concentration and the hemoglobin content, and for the shares of basophile granulocytes, platelets and lymphocytes. No meaningful shares of additive genetic variance were obvious in the other traits. Shares of additive genetic variance of the above mentioned traits argue for the existence of favourable and unfavourable gene variants to be involved in their phenotypic variation. Isolation of these variants might improve the diagnostical use of those traits in the future and provide a measure to advance general health in the pig.

Quantitative trait loci for red blood cell traits in swine.

Haematological traits are essential diagnostic parameters in veterinary practice but knowledge on the genetic architecture controlling variability of erythroid traits is sparse, especially in swine. To identify QTL for erythroid traits in the pig, haematocrit (HCT), haemoglobin (HB), erythrocyte counts (RBC) and mean corpuscular haemoglobin content (MCHC) were measured in 139 F(2) pigs from a Meishan/Pietrain family, before and after challenge with the protozoan pathogen Sarcocystis miescheriana. The pigs passed through three stages representing acute disease, reconvalescence and chronic disease. Forty-three single QTL controlling erythroid traits were identified on 16 chromosomes. Twelve of the QTL were significant at the genome-wide level while 31 were significant at a chromosome-wide level. Because erythroid traits varied with health and disease status, QTL influencing the erythroid phenotypes showed specific health/disease patterns. Regions on SSC5, 7, 8, 12 and 13 contained QTL for baseline erythroid traits, while the other QTL regions affected distinct stages of the disease model. Single QTL explained 9-17% of the phenotypic variance in the F(2) animals. Related traits were partly under common genetic influence. Our analysis confirms that erythroid trait variation differs between Meishan and Pietrain breeds and that this variation is associated with multiple chromosomal regions.

Genetic resistance to Sarcocystis miescheriana in pigs following experimental infection.

Clinical and parasitological traits of Sarcocystis miescheriana differ in Pietrain and Meishan pigs. For further description and characterization of the genetic basis of this variation a F(2) family based on Pietrain boars and Meishan sows as founders was generated. One hundred and thirty-nine F(2) pigs were challenged orally at an age of 100 days with 50,000 sporozysts to produce the typical clinical picture of a moderate dose Sarcocystis infection. Heritabilities were estimated for clinical and clinical-chemical traits, for specific antibody responses to the infection and for bradyzoite numbers found in skeletal (Musculus longissimus dorsi: M.l.d.) and heart muscles at necropsy 70 days post-infection (p.i.) Apart from several low to moderate heritabilities, high heritabilities were observed for bradyzoite numbers in the M.l.d. (0.68), IgM antibody levels (0.74) during the acute (14 days p.i.) and titres of specific IgG antibodies (0.42) in the early stage of cyst formation (42 days p.i.). Marked heritabilities of these traits, which are basic for acute phase of the disease (14 days p.i.) or chronic Sarcocystosis presume genes that explain sufficient shares of variance (QTL). The model is considered valuable for screening of gene variants associated with resistance/susceptibility to Sarcocystis infection. Such gene variants could then be used in susceptibility-scoring or selection programs in the future.

[Vasectomy: indications and implementation in historic perspective]. / Vasectomie: indicaties en uitvoering in een historisch perspectief.

Approximately 35,000 vasectomies were performed in the Netherlands in 2004. Although vasectomy may be looked upon as the most reliable method of contraception (risk of pregnancy in the first year: 0.08-0.15%), realistic preoperative counselling about possible complications such as haemorrhage (5%), wound infection (5%), and haematoma (14%) and long-term consequences such as the wish for renewed fertility (2.6% of the men opt for vasectomy reversal), the delayed achievement of sterility (4% three months after vasectomy), chronic scrotalgia (5%) and the risk of recanalisation (0.28-00.5%) is of utmost importance. Moreover, the couple should be convinced that vasectomy can only be considered successful if less than 100,000 non-motile sperms per ml are demonstrated by a certified laboratory in a post-vasectomy semen analysis. As an alternative for vasectomy, several clinical studies to assess the value of male hormonal contraception are currently in progress.

The contact Nd:YAG laser: a new technique for conservation of the fallopian tube in unruptured ectopic pregnancy.

Between August 1986 and April 1988, 22 women with unruptured tubal pregnancy were treated by laparoscopy in the Department of Gynaecology and Obstetrics at the University of Ulm. Linear salpingotomy was performed using the contact Nd:YAG laser technique. The laser beam was delivered by special sapphire probes attached to a standard optical fibre for incision and coagulation. Two different shapes of sapphire probes were used. The specific laser properties and the application of vasopressin enabled treatment without any other incision instruments or coagulation agents. In one patient subsequent laparoscopy became necessary due to persisting trophoblastic tissue. Sixteen women were assessed subsequently by second-look laparoscopy or hysterosalpingography for tubal patency and possible formation of adhesions. In 14 (88%) women the tubes were patent, and in two women adhesions were seen.

[Tube-preserving endoscopic surgical procedures in unruptured tubal pregnancy. What significance does laser use have?]. / Tubenerhaltende endoskopische Operationsverfahren bei nicht rupturierter Tubargravidität. Welche Bedeutung hat dabei der Laser-Einsatz?

Between 1985 and 1989 115 non-ruptured tubal pregnancies were operated upon, using a pelviscope and preserving of the tube. For the purpose of prophylactic haemostasis 2,5 I.U. ornipressin (Por 8) were injected into the mesosalpinx. The tube was opened (linear salpingotomy) by using various instruments. This method was used in 49 patients by means of the thermocoagulator and hooked scissors; with the remaining 66 patients the following laser systems were employed: CO2-laser (n = 13); Nd: YAG-laser by the contact method (n = 22); argon-laser (n = 31). No intraoperative complications were noted. Postoperative rebleeding occurred in three patients requiring subsequent treatment, and pelviscopy had to be repeated in two patients, because of incompletely removed trophoblastic tissue. The tubal condition (patency; occurrence of adhesion) was checked in 53 (47%) of the patients by means of hysterosalpingography (n = 15) or second-look pelviscopy (n = 38). Tubal patency/peritubal adhesion were found after conventional surgery in 64%/55% of the controlled cases and after laser salpingotomy in 90%/11%, respectively. Summing up, we can say, that the various laser systems are suitable for operating non-ruptured pregnancies due to their accurate incision and simultaneously coagulating effect. Due to the lower postoperative tubal occlusion rate and lower tendency to adhesion, it appears, that the laser systems are superior to the conventional endoscopy instruments, although the rate of complications was highest after CO2-laser application.