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For some who see me in a wheelchair, I represent "their worst nightmare." Others, however, see me as an "inspiration." Both of these labels have three things in common: they are wrong; they deny my humanity; and they speak more about the "asker" than about me. How, I wonder, does God see me? [ABSTRACT FROM AUTHOR]

Background: Mycoplasma suis (M. suis) belongs to the group of haemotrophic mycoplasmas and is known as the causative agent of infectious anaemia in pigs. In the last few years valuable insights into the mechanism of adhesion and invasion, shedding patterns and cell tropism of M. suis were gained by the use of new molecular techniques. However, details on M. suis induced lesions as well as the distribution of M. suis in different organs are still lacking. Therefore, seven splenectomised pigs were experimentally infected and clinical and laboratory investigations as well as a detailed histopathological examination were performed. Detection and quantification of M. suis DNA in blood and various tissue samples was done using a quantitative real-time PCR. Results: During the course of experimental infection, periodically occurring signs of infectious anaemia of pigs including severe icteroanaemia, fever, apathy and anorexia were observed. In addition, dermatological manifestations such as haemorrhagic diathesis presenting as petechiae occurred. The most important haematological alterations were normochromic, normocytic anaemia, hypoglycaemia as well as increased bilirubin and urea concentrations. Necropsy revealed predominant evidence of haemolysis with consecutive anaemia, as well as disseminated intravascular coagulation. M. suis was found in all investigated tissues with the highest copy numbers found in the kidneys. In Giemsa stained sections M. suis was only detected red blood cell (RBC)-associated. Conclusion: In the present study, no RBC independent sequestration of M. suis was detected in organs of experimentally infected pigs. Pathological findings are most likely resulting from haemolysis, consecutive anaemia as well as from disseminated intravascular coagulation and subsequent organ impairments. [ABSTRACT FROM AUTHOR]

Maturity onset diabetes of the young (MODY) is a monogenic form of diabetes inherited as an autosomal dominant trait. The second most common cause is GCK-MODY due to heterozygous mutations in the GCK gene which impair the glucokinase function through different mechanisms such as enzymatic activity, protein stability, and increased interaction with its receptor. The enzyme normally acts as a glucose sensor in the pancreatic beta cell and regulates insulin secretion. We report here a three- generation nonobese family diagnosed with diabetes. All affected family members presented with mild hyperglycemia and mostly slightly elevated hemoglobin A1c values. Genetic testing revealed a novel heterozygous T → C exchange in exon 8 of the GCK gene which resulted in a phenylalanine-330 TTC → serine (TCC)/p.Phe330Ser/F330S substitution. [ABSTRACT FROM AUTHOR]

Borrelia persica, a bacterium transmitted by the soft tick Ornithodoros tholozani, causes tick-borne relapsing fever in humans in the Middle East, Central Asia and the Indian peninsula. Immunocompetent C3H/HeOuJ mice were infected intradermally with B. persica at varying doses: 1 x 106, 1 x 104, 1 x 102 and 4 x 100 spirochetes/mouse. Subsequently, blood samples were collected and screened for the presence of B. persica DNA. Spirochetes were detected in all mice infected with 1 x 106, 1 x 104 and 1 x 102 borrelia by real-time PCR targeting the flaB gene of the bacterium. Spirochetemia developed with a one- to two-day delay when 1 x 104 and 1 x 102 borrelia were inoculated. Mice injected with only four organisms were negative in all tests. No clinical signs were observed when infected mice were compared to negative control animals. Organs (heart, spleen, urinary bladder, tarsal joint, skin and brain) were tested for B. persica-specific DNA and cultured for the detection of viable spirochetes. Compiled data show that the target organs of B. persica infections are the brain and the skin. A newly developed serological two-tiered test system (ELISA and western blot) for the detection of murine IgM, IgG and IgA antibody titers against B. persica showed a vigorous antibody response of the mice during infection. In conclusion, the infection model described here for B. persica is a platform for in vivo studies to decipher the so far unexplored survival strategies of this Borrelia species. [ABSTRACT FROM AUTHOR]

Despite the high potential of healthy bone to regenerate, the reconstruction of large bone defects remains a challenge. Due to the lack of mechanical stability of existing bone substitutes, recently developed degradable metallic alloys are an interesting alternative providing higher load-bearing capabilities. Degradable iron-based alloys therefore might be an attractive innovation. To test the suitability of a newly-designed iron-based alloy for such applications, an animal experiment was performed. Porous iron-based degradable implants with two different densities and a control group were tested. The implants were positioned in the proximal tibia of Merino sheep. Over a period of 6 and 12 months, blood and histological parameters were monitored for signs of inflammation and degradation. In the histological evaluation of the implants' environment we found degraded alloy particles, but no inflammatory reaction. Iron particles were also found within the popliteal lymph nodes on both sides. The serum blood levels of phosphorus, iron and ferritin in the long term groups were elevated. Other parameters did not show any changes. Iron-based degradable porous bone replacement implants showed a good biocompatibility in this experiment. For a clinical application, however, the rate of degradation would have to be significantly increased. Biocompatibility would then have to be re-evaluated. [ABSTRACT FROM AUTHOR]

Bone replacement and osteosynthesis require materials which can at least temporarily bear high mechanical loads. Ideally, these materials would eventually degrade and would be replaced by bone deposited from the host organism. To date several metals, notably iron and iron-based alloys have been identified as suitable materials because they combine high strength at medium corrosion rates. However, currently, these materials do not degrade within an appropriate amount of time. Therefore, the aim of the present study is the development of an iron-based degradable sponge-like (i.e. cellular) implant for bone replacement with biomechanically tailored properties. We used a metal powder sintering approach to manufacture a cylindrical cellular implant which in addition contains phosphor as an alloying element. No corrosion inhibiting effects of phosphorus have been found, the degradation rate was not altered. Implant prototypes were tested in an animal model. Bone reaction was investigated at the bone-implant-interface and inside the cellular spaces of the implant. Newly formed bone was growing into the cellular spaces of the implant after 12 months. Signs of implant degradation were detected but after 12 months, no complete degradation could be observed. In conclusion, iron-based open-porous cellular biomaterials seem promising candidates for the development of self-degrading and high load bearing bone replacement materials. [ABSTRACT FROM AUTHOR]

The objective of the present study was to assess safety and immune responses in gilts after intradermal application of Porcilis® PRRS in two different application sites under field conditions. Forty-four gilts were allocated to one of three groups: Gilts of group 1 (n = 10) served as non-vaccinated controls, gilts of group 2 (n = 17) were vaccinated intradermally in the neck and gilts of group 3 (n = 17) received an intradermal vaccination in the perianal region. Clinical observations, local injection site reactions and histopathologic examination of the injection site were used for safety assessments. Frequency and degree of clinical signs were not significantly different between all three groups. Minor local reactions for both vaccination groups were observed; however, at 6, 7, 8, 9 and 15 days post-vaccination (dpv), the mean injection site reaction score was significantly lower in pigs vaccinated in the perianal region. In histopathologic examination, an extended inflammatory dimension was observed more frequently in pigs vaccinated in the neck. Blood samples were analyzed to quantify the post-vaccination humoral (ELISA and virus neutralization test) and cellular (IFN-γ ELISPOT) immune responses. PRRSV-specific antibodies were present in the serum of all vaccinated animals from 14 dpv onwards, whereas all control pigs remained negative throughout the study. Neutralizing antibody titers were significantly higher in pigs vaccinated in the perianal region at 28 dpv. At 14, 21 and 28 dpv, PRRSV-specific IFN-γ secreting cells were significantly increased in both vaccination groups compared to non-vaccinated gilts. Analysis of mean numbers of PRRSV-specific IFN-γ secreting cells did not result in statistically significant differences between both vaccination groups. The results of this study indicate that the perianal region is a safe alternative application site for intradermal vaccination of gilts with Porcilis PRRS. Furthermore, the intradermal application of Porcilis PRRS induced humoral and cellular immune responses independent of the administration site. [ABSTRACT FROM AUTHOR]

Safety testing is one major part of the licensing procedure for veterinary vaccines and demands a large number of animals. Magnetic resonance imaging (MRI) was tested as an alternative, which may lead to a reduction in numbers of animals required for safety testing, and, correspondingly to a detailed description of the three-dimensional extent of the local tissue reaction repetitively in live pigs. In previous pig studies the following questions arose: (1) Can MRI be used in suckling pigs in terms of safety testing? (2) Does the injection of 2 ml saline solution lead to a volume effect resulting in tissue alterations comparable to a vaccine response? (3) Is the local reaction size affected by the tattoo marking of the injection point for the final pathomorphologic examination? To answer these questions the following study was performed by comparing two vaccine groups of suckling piglets (8 animals per group; A and B) with two control groups (4 animals per group; C and D). One control group was injected with a saline solution (C) and the other was only tattoo marked (D). The animals were examined using MRI at days 1, 8, 15, 22, 29, 36, and 43 post vaccination, ending with a final pathomorphologic examination. Pathomorphologic examination confirmed MRI findings. Saline solution does not result in a local tissue reaction as detected after injecting vaccines. Tattoo marking causes no local tissue reaction, neither in MRI nor in pathomorphologic examination. Therefore, MRI can be used as an alternative method for safety testing of vaccines in pigs of different age categories offering repetitive measurements of local tissue reactions. Involved cells might be examined only in a final pathomorphologic examination at the end of the trial on a reduced number of animals. [ABSTRACT FROM AUTHOR]

Abstract: The expression of a dominant negative glucose-dependent insulinotropic polypeptide receptor (GIPRdn) under the control of the rat pro-insulin gene promoter induces severe diabetes mellitus in transgenic mice. This study aims to gain further insight into the effect of the expression of a dominant negative GIPR on glucose homeostasis and postnatal development of the endocrine pancreas. The diabetic phenotype of GIPRdn transgenic animals was first observed between 14 and 21 days of age (urine glucose >1000 mg/dl). After onset of diabetes, serum glucose was significantly higher and insulin values were significantly lower in GIPRdn transgenic mice vs. non-transgenic littermate controls. Morphometric studies of pancreatic islets and their endocrine cell types were carried out at 10, 30 and 90 days of age. The total islet and total beta-cell volume of transgenic mice was severely reduced as compared to control mice, irrespective of the age at sampling (p<0.05). The total volume of isolated insulin positive cells that were not contained within established islets was significantly reduced in transgenic mice, indicating disturbed islet neogenesis. These findings demonstrate in vivo evidence that intact signaling of G-protein coupled receptors is involved in postnatal islet and beta-cell development and neogenesis of the pancreatic islets. [Copyright &y& Elsevier]

Summary Growth hormone has been shown to possess stimulatory effects on various connective tissues. We observed that skin growth in male rat phosphoenolpyruvate carboxykinase-bovine growth hormone transgenic mice (serum growth hormone levels: 740–1940 ng per ml) is progressive with age, resulting in an ‘‘oversized coat’’ phenotype with a marked increase in absolute and relative skin weight and surface area, and in thickness of the dermis. Histologic changes include severe dermal fibrosis and replacement of subdermal adipose tissue by fibrous tissue. Apart from an increase in skin surface area, these changes were not noted in female transgenic mice, arguing for a specific interaction of growth hormone with male sex hormones. To clarify this point, 6 wk old male transgenic mice and control mice were castrated and compared with their noncastrated counterparts in parameters of skin growth at an age of 8 mo. The skin weight of castrated transgenic mice was smaller (p < 0.01) than that of intact transgenic mice both absolutely and relative to body weight. The relative skin weight of castrated transgenic mice was in the same range as in intact and castrated control mice. Absolute and relative skin area of castrated transgenic mice was greater (p < 0.001 and p < 0.05) than in controls but lower than in intact transgenic mice (p < 0.001 and p < 0.05). When compared with control mice, intact transgenic mice displayed an increase (p < 0.01) in the thickness of dermis. In castrated transgenic mice the thickness of the dermis was in the same range as in control mice. Our findings demonstrate a specific interaction of growth hormone with male sex hormones resulting in a marked stimulation of skin growth. [ABSTRACT FROM AUTHOR]

The article describes the case of Mycobacterium celatum infection in a ferret, with possible transmission to a human. Physical manifestations include coughing, vomiting and mild diarrhea, among others. It explains that M. celatum in humans affects immunocompromised hosts with developing pneumonia or disseminated mycobacteriosis. It suggests the possibility of airborne spread of mycobacteria detected from the ferret's lung and infection of humans. It recommends M. celatum infection to be strongly considered as a differential diagnosis in ferrets with pneumonia and generalized lymphatic hyperplasia.