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Simple Summary: There is a disadvantage in determining the amino acid digestibility of swine feed ingredients using commercial cannulated pigs due to their relatively fast growth rate. Using mini-pig breeds to determine the amino acid digestibility can complement this disadvantage of commercial pigs. Therefore, the objective of this study was to compare the ileal digestibility of crude protein and amino acids between commercial crossbred pigs and Jeju Island native pigs. The digestibility of most amino acids was comparable between the two breeds regardless of the test ingredient. These findings indicate that amino acid digestibility data from Jeju Island native pigs can be used to estimate the amino acid digestibility in feedstuffs for commercial crossbred pigs. The objectives of this study were to determine the apparent ileal digestibility and standardized ileal digestibility (SID) of crude protein (CP) and amino acids (AA) in feed ingredients, compare the ileal digestibility of CP and AA between commercial crossbred pigs and mini-Jeju Island native pigs (JINP), and develop models for estimating SID of CP and AA for commercial pigs using mini-JINP data. The study involved five crossbred commercial pigs (31.5 ± 1.6 kg of body weight and 11 weeks of age; Landrace × Yorkshire) and five mini-JINP (31.0 ± 3.2 kg body weight and 20 weeks of age). The pigs were surgically equipped with a T-cannula at the end of ileum. Each pig breed was assigned to 5 dietary treatments in a 5 × 10 incomplete Latin square design with 10 periods. Four experimental diets were formulated to contain each of soybean meal, corn gluten feed, copra meal, and sesame expellers as the sole source of nitrogen. A nitrogen-free diet was also prepared to determine basal endogenous losses of CP and AA. No interaction between breed and feed ingredient was observed for the digestibility of CP and all indispensable AA. The SID of CP and all indispensable AA, except Arg, His, and Lys, did not differ between the two breeds of pigs. Prediction equations were developed for SID of CP and AA of commercial pigs using the SID values of mini-JINP: SID of CP (%) = (1.02 × SID of CP in mini-JINP) − 5.20 with r2 = 0.97 and p < 0.05; SID of Lys (%) = (1.12 × SID of Lys in mini-JINP) − 9.10 with r2 = 0.98 and p < 0.05; and SID of Met (%) = (1.08 × SID of Met in mini-JINP) − 4.27 with r2 = 0.96 and p < 0.05. The digestibility for most AA in feedstuffs for commercial pigs can be estimated using data from mini-JINP. [ABSTRACT FROM AUTHOR]

Post-traumatic spinal cord remodeling includes both degenerating and regenerating processes, which affect the potency of the functional recovery after spinal cord injury (SCI). Gene therapy for spinal cord injury is proposed as a promising therapeutic strategy to induce positive changes in remodeling of the affected neural tissue. In our previous studies for delivering the therapeutic genes at the site of spinal cord injury, we developed a new approach using an autologous leucoconcentrate transduced ex vivo with chimeric adenoviruses (Ad5/35) carrying recombinant cDNA. In the present study, the efficacy of the intravenous infusion of an autologous genetically-enriched leucoconcentrate simultaneously producing recombinant vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) was evaluated with regard to the molecular and cellular changes in remodeling of the spinal cord tissue at the site of damage in a model of mini-pigs with moderate spinal cord injury. Experimental animals were randomly divided into two groups of 4 pigs each: the therapeutic (infused with the leucoconcentrate simultaneously transduced with a combination of the three chimeric adenoviral vectors Ad5/35‐VEGF165, Ad5/35‐GDNF, and Ad5/35‐NCAM1) and control groups (infused with intact leucoconcentrate). The morphometric and immunofluorescence analysis of the spinal cord regeneration in the rostral and caudal segments according to the epicenter of the injury in the treated animals compared to the control mini-pigs showed: (1) higher sparing of the grey matter and increased survivability of the spinal cord cells (lower number of Caspase-3-positive cells and decreased expression of Hsp27); (2) recovery of synaptophysin expression; (3) prevention of astrogliosis (lower area of glial fibrillary acidic protein-positive astrocytes and ionized calcium binding adaptor molecule 1-positive microglial cells); (4) higher growth rates of regenerating βIII-tubulin-positive axons accompanied by a higher number of oligodendrocyte transcription factor 2-positive oligodendroglial cells in the lateral corticospinal tract region. These results revealed the efficacy of intravenous infusion of the autologous genetically-enriched leucoconcentrate producing recombinant VEGF, GDNF, and NCAM in the acute phase of spinal cord injury on the positive changes in the post-traumatic remodeling nervous tissue at the site of direct injury. Our data provide a solid platform for a new ex vivo gene therapy for spinal cord injury and will facilitate further translation of regenerative therapies in clinical neurology.

Abstract Background Currently, increasing attention is being paid to the important role of intestinal microbiome in diabetes. However, few studies have evaluated the characteristics of gut microbiome in diabetic miniature pigs, despite it being a good model animal for assessing diabetes. Methods In this study, a mini‐pig diabetes model (DM) was established by 9‐month high‐fat diet (HFD) combined with low‐dose streptozotocin, while the animals fed standard chow diet constituted the control group. 16S ribosomal RNA (rRNA) gene sequencing was performed to assess the characteristics of the intestinal microbiome in diabetic mini‐pigs. Results The results showed that microbial structure in diabetic mini‐pigs was altered, reflected by increases in levels of Coprococcus_3 and Clostridium_sensu_stricto_1, which were positively correlated with diabetes, and decreases in levels of the bacteria Rikenellaceae, Clostridiales_vadinBB60_group, and Bacteroidales_RF16_group, which were inversely correlated with blood glucose and insulin resistance. Moreover, PICRUSt‐predicted pathways related to the glycolysis and Entner‐Doudoroff superpathway, enterobactin biosynthesis, and the l‐tryptophan biosynthesis were significantly elevated in the DM group. Conclusion These results reveal the composition and predictive functions of the intestinal microbiome in the mini‐pig diabetes model, further verifying the relationship between HFD, gut microbiome, and diabetes, and providing novel insights into the application of the mini‐pig diabetes model in gut microbiome research.

The natural limitations of regeneration in the CNS are major problems for the treatment of neurological disorders, including ischaemic brain strokes. Among the approaches being actively developed to inhibit post-ischaemic negative consequences is the delivery of therapeutic genes encoding neuroprotective molecules to the brain. Unfortunately, there are currently no proven and available medicines that contain recombinant human genes for the treatment of ischaemic cerebral stroke. Of particular interest is the development of treatments for patients at risk of ischaemic stroke. In the present study, we propose a proof of concept for the use of an autologous, genetically enriched leucoconcentrate temporally secreting recombinant vascular endothelial growth factor (VEGF), glial-cell-line-derived neurotrophic factor (GDNF) and the neural cell adhesion molecule (NCAM) for the treatment of stroke. In a mini-pig ischaemic stroke model, genetically enriched leucoconcentrate was infused 4 h after surgery (gene therapy in acute phase) or 2 days before stroke modelling (preventive gene therapy). On day 21, after the stroke modelling, the post-ischaemic brain recovery was examined by morphologic and immunofluorescence analysis. The benefits of treating a stroke with genetically enriched leucoconcentrate both for preventive purposes and in the acute phase were confirmed by an improved performance in behavioural tests, higher preservation of brain tissue and positive post-ischaemic brain remodelling in the peri-infarct area. These results suggest that the employment of autologous leucocytes enabling the temporary production of the recombinant therapeutic molecules to correct the pathological process in the CNS may be one of the breakthrough approaches in gene therapy. [ABSTRACT FROM AUTHOR]

Purpose: The increasing number of implant-associated infections during trauma and orthopedic surgery caused by biofilm-forming Staphylococcus aureus in combination with an increasing resistance of conventional antibiotics requires new therapeutic strategies. One possibility could be testing for different therapeutic strategies with differently coated plates. Therefore, a clinically realistic model is required. The pig offers the best comparability to the human situation, thus it was chosen for this model. The present study characterizes a novel model of a standardized low-grade acute osteitis with bone defect in the femur in mini-pigs, which is stabilized by a titanium locking plate to enable further studies with various coatings. Methods: A bone defect was performed on the femur of 7 Aachen mini-pigs and infected with Methicillin-resistant S. aureus (MRSA ATCC 33592). The defect zone was stabilized with a titanium plate. After 14 days, a plate change, wound debridement and lavage were performed. Finally, after 42 days, the animals were lavaged and debrided again, followed by euthanasia. The fracture healing was evaluated radiologically and histologically. Results: A local osteitis with radiologically visible lysis of the bone could be established. The unchanged high Colony-forming Units (CFU) in lavage, the significant differences in Interleukin (IL)-6 in blood compared to lavage and the lack of increase in Alkaline Phosphates (ALP) in serum over the entire observation period show the constant local infection. Conclusion: The study shows the successful induction of local osteitis with lysis of the bone and the lack of enzymatic activity to mineralize the bone. Therefore, this standardized mini-pig model can be used in further clinical studies, to investigate various coated implants, bone healing, biofilm formation and immune response in implant-associated osteitis. [ABSTRACT FROM AUTHOR]

Abstract Background Radiation-induced brain injury is a common concern for survivors of adult and pediatric brain cancer. Pre-clinically, rodent models are the standard approach to evaluate mechanisms of injury and test new therapeutics for this condition. However, these rodent models fail to recapitulate the radiological and histological characteristics of the clinical disease. Methods Here we describe a hemispheric mini-pig model of radiation-induced brain injury generated with a clinical 6 MV photon irradiator and evaluated with a clinical 3T MRI. Two pairs of Yucatan mini-pigs each received either 15 Gy or 25 Gy to the left brain hemisphere. Quality of intensity modulated radiation therapy treatment plans was evaluated retrospectively with parameters reported according to ICRU guidelines. The pigs were observed weekly to check for any outright signs of neurological impairment. The pigs underwent anatomical MRI examination before irradiation and up to 6 months post-irradiation. Immediately after the last imaging time point, the pigs were euthanized and their brains were collected for histopathological assessment. Results Analysis of the dose volume histograms showed that 93% of the prescribed dose was delivered to at least 93% of the target volume in the left hemisphere. Organs at risk excluded from the target volume received doses below clinical safety thresholds. For the pigs that received a 25 Gy dose, progressive neurological impairment was observed starting at 2 months post-irradiation leading to the need for euthanasia by 3–4 months. On MRI, these two animals presented with diffuse white matter pathology consistent with the human disease that progressed to outright radiation necrosis and severe brain swelling. Histology was consistent with the final MRI evaluation. The pigs that received a 15 Gy dose appeared normal all the way to 6 months post-irradiation with no obvious neurological impairment or lesions on MRI or histopathology. Conclusion Based on our results, a mini-pig model of radiation-induced brain injury is feasible though some optimization is still needed. The mini-pig model produced lesions on MRI that are consistent with the human disease and which are not seen in rodent models. Our data shows that the ideal radiation dose for this model likely lies between 15 and 25 Gy.

Dapagliflozin base and a commercial dapagliflozin propanediol hydrate cocrystal (DPF-PDHC) were highly hygroscopic and thermally unstable. In this study, to address this limitation, we prepared a novel dapagliflozin di-L-proline cocrystal (DPF-LPC) and evaluated its physicochemical characterization compared with DPF-PDHC. After the preparation of the DPF-LPC-loaded tablet, its dissolution, stability and bioequivalence in beagle dogs and mini-pigs were assessed. DPF-LPC was well prepared with a dapagliflozin base and L-proline in a molar ratio of 1:2. Similar to DPF-PDHC, DPF-LPC was highly lipophilic and crystalline in nature. However, these two cocrystals exhibited different melting points and crystalline structures, indicating their different cocrystal forms. Moreover, DPF-LPC exhibited less hygroscopicity and lower water content than DPF-PDHC. The DPF-LPC-loaded tablet composed of DPF-LPC, Comprecel M102, lactose monohydrate, crospovidone, magnesium stearate, and Opadry (coating) at a weight ratio of 15.6:104.4:100.0:8.0:2.0:7.0, was dissolution-equivalent to the commercial tablet. Moreover, it provided lower impurities than the commercial tablet, indicating its better stability. In the two animals, there were no significant differences in the plasma concentrations, AUC, Cmax, and Tmax values, suggesting that they were bioequivalent. Therefore, the novel DPF-LPC-loaded tablet with excellent stability and bioequivalence may be used as a potential alternative to the commercial DPF-PDHC-loaded tablet. [ABSTRACT FROM AUTHOR]

Background: Radiation-induced brain injury is a common concern for survivors of adult and pediatric brain cancer. Pre-clinically, rodent models are the standard approach to evaluate mechanisms of injury and test new therapeutics for this condition. However, these rodent models fail to recapitulate the radiological and histological characteristics of the clinical disease.Methods: Here we describe a hemispheric mini-pig model of radiation-induced brain injury generated with a clinical 6 MV photon irradiator and evaluated with a clinical 3T MRI. Two pairs of Yucatan mini-pigs each received either 15 Gy or 25 Gy to the left brain hemisphere. Quality of intensity modulated radiation therapy treatment plans was evaluated retrospectively with parameters reported according to ICRU guidelines. The pigs were observed weekly to check for any outright signs of neurological impairment. The pigs underwent anatomical MRI examination before irradiation and up to 6 months post-irradiation. Immediately after the last imaging time point, the pigs were euthanized and their brains were collected for histopathological assessment.Results: Analysis of the dose volume histograms showed that 93% of the prescribed dose was delivered to at least 93% of the target volume in the left hemisphere. Organs at risk excluded from the target volume received doses below clinical safety thresholds. For the pigs that received a 25 Gy dose, progressive neurological impairment was observed starting at 2 months post-irradiation leading to the need for euthanasia by 3-4 months. On MRI, these two animals presented with diffuse white matter pathology consistent with the human disease that progressed to outright radiation necrosis and severe brain swelling. Histology was consistent with the final MRI evaluation. The pigs that received a 15 Gy dose appeared normal all the way to 6 months post-irradiation with no obvious neurological impairment or lesions on MRI or histopathology.Conclusion: Based on our results, a mini-pig model of radiation-induced brain injury is feasible though some optimization is still needed. The mini-pig model produced lesions on MRI that are consistent with the human disease and which are not seen in rodent models. Our data shows that the ideal radiation dose for this model likely lies between 15 and 25 Gy. [ABSTRACT FROM AUTHOR]

Abstract Background This study compares a traditional parapatellar retinaculum-sacrificing arthrotomy to a retinaculum-sparing arthrotomy in a porcine stifle joint as a cartilage repair model. Findings Surgical exposure of the femoral trochlea of ten Yucatan pigs stifle joint was performed using either a traditional medial parapatellar approach with retinaculum incision and luxation of the patella (n = 5) or a minimally invasive (MIS) approach which spared the patellar retinaculum (n = 5). Both classical and MIS approaches provided adequate access to the trochlea, enabling the creation of cartilage defects without difficulties. Four full thickness, 4 mm circular full-thickness cartilage defects were created in each trochlea. There were no intraoperative complications observed in either surgical approach. All pigs were allowed full weight-bearing and full range of motion immediately postoperatively and were euthanized between 2 and 3 weeks. The traditional approach was associated with increased cartilage wear compared to the MIS approach. Two blinded raters performed gross evaluation of the trochlea cartilage surrounding the defects according to the modified ICRS cartilage injury classification. The traditional approach cartilage received a significantly worse score than the MIS approach group from both scorers (3.2 vs 0.8, p = 0.01 and 2.8 vs 0, p = 0.005 respectively). Conclusion The MIS approach results in less damage to the trochlear cartilage and faster return to load bearing activities. As an arthrotomy approach in the porcine model, MIS is superior to the traditional approach.

The objective of this study was to investigate the effects of different growth factors on the proliferation of Bama mini‐pig spermatogonial stem cells (SSCs) in vitro. The growth factors glial cell line‐derived neurotrophic factor (GDNF), leukaemia inhibitory factor (LIF), GDNF family receptor alpha‐1 (GFRα1) and basic fibroblast growth factor (bFGF) were investigated. The SSCs were seeded on SIM mouse embryo‐derived thioguanine‐ and ouabain‐resistant (STO) feeder layers. Cultivation of the cells were subjected to a factorial design of the growth factors GDNF + bFGF, GDNF + bFGF + GFRα1, LIF + bFGF and LIF + bFGF + GFRα1. The SSCs could propagate for 25 passages in the medium adding GDNF + bFGF + GFRα1, 22 passages in the medium adding GDNF + bFGF, 6 passages in the medium adding LIF + bFGF, or LIF + bFGF + GFRα1. qRT‐PCR analysis showed that the highest mRNA expression levels of NANOG, POU5F, DDX4, GFRα1 and UCHL1 were detected in the group adding GDNF + bFGF + GFRα1. The SSCs from the group adding GDNF + bFGF + GFRα1 also showed UCHL1‐, DBA‐ and CDH1‐positive staining. Moreover, Stra8 and Scp3 expression, and haploid peak were detected after induction of the SSCs from the group adding GDNF + bFGF + GFRα1. In conclusion, pig SSCs could be maintained for long term in the presence of GDNF, bFGF, and GFRα1. [ABSTRACT FROM AUTHOR]

Obesity induced by overfeeding ultimately can lead to nonalcoholic fatty liver disease, whereas dietary fiber consumption is known to have a beneficial effect. We aimed to determine if a supplementation of a mix of fibers (inulin, resistant starch and pectin) could limit or alleviate overfeeding-induced metabolic perturbations. Twenty female minipigs were fed with a control diet (C) or an enriched fat/sucrose diet supplemented (O + F) or not (O) with fibers. Between 0 and 56 days of overfeeding, insulin (+88%), HOMA (+102%), cholesterol (+45%) and lactate (+63%) were increased, without any beneficial effect of fibers supplementation. However, fibers supplementation limited body weight gain (vs. O, -15% at D56) and the accumulation of hepatic lipids droplets induced by overfeeding. This could be explained by a decreased lipids transport potential (-50% FABP1 mRNA, O + F vs. O) inducing a down-regulation of regulatory elements of lipids metabolism / lipogenesis (-36% SREBP1c mRNA, O + F vs. O) but not to an increased oxidation (O + F not different from O and C for proteins and mRNA measured). Glucose metabolism was also differentially regulated by fibers supplementation, with an increased net hepatic release of glucose in the fasted state (diet × time effect, P<.05 at D56) that can be explained partially by a possible increased glycogen synthesis in the fed state (+82% GYS2 protein, O + F vs. O, P=.09). The direct role of short chain fatty acids on gluconeogenesis stimulation is questioned, with probably a short-term impact (D14) but no effect on a long-term (D56) basis. [ABSTRACT FROM AUTHOR]

Abstract Background It has been noted that anterior cruciate ligament (ACL) injury-induced cartilage degeneration is the key risk factor for post-traumatic osteoarthritis (PTOA). However, whether the cartilage degeneration after ACL injury is caused by inflammation, abnormal biomechanics or both remains largely unknown, as there has been no animal model for separating the two factors so far. Methods Eighteen-month-old female mini-pigs were divided into an "idealized" anterior cruciate ligament reconstruction (IACLR) group and a control group (n = 16 limbs per group). Real-time PCR, safranine O staining and indian ink staining were performed to verify whether animal models were successfully established or not. Multiple linear regression analysis was used to evaluate the correlation between levels of the inflammatory factors (including interferon [IFN]-γ, interleukin [IL]-1β, IL-4, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor [TNF]-α measured by the Luminex method) and changes in cartilage histology (quantified by morphological scoring) after surgery. Results A significant OA cartilage damage with increased MMP-1, MMP-13 mRNA levels and reduced aggrecan mRNA/protein levels was observed in IACLR groups. As a result, the IACLR gross morphology score was dramatically increased than control. Moreover, IACLR significantly increased the levels of IL-1β, IL-4, IL-6 and TNF-α in the synovial fluid of the knee. Most importantly, a close relationship was found between IL-1β, IL-6 and TNF-α concentrations and morphological score of PTOA, respectively. Conclusion These results demonstrated that inflammatory factors are independently responsible for the onset of PTOA. Highlights • An "idealized" anterior cruciate ligament reconstruction (IACLR) model using mini-pigs innovatively was developed. • This study, for the first time, proves that inflammatory factors are independently responsible for the onset of PTOA. • Luminex liquid chip is used to detect inflammatory factors in synovial fluid. [ABSTRACT FROM AUTHOR]

Although the rat is close to being the automatic choice for regulatory juvenile toxicity studies, there are several shortcomings in this model. Choosing a species should take into serious consideration the importance of gastrointestinal tract development in the period before weaning as this may have a major effect on exposure. A comparison of the anatomical changes in the stomach and small intestine of mini‐pig and rat show that the mini‐pig is a far closer model for man than is the rat, although there are a few unusual aspects of small intestinal development in the mini‐pig. Considerations of the development of the gastrointestinal tract and choice of species have the potential to affect safety assessment and should be a prime consideration when planning an investigation. Birth Defects Research 110:56–62, 2018. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The pathogenic mechanism of polycystic kidney disease (PKD) is unclear. Abnormal glucose metabolism is maybe involved in hyper-proliferation of renal cyst epithelial cells. Mini-pigs are more similar to humans than rodents and therefore, are an ideal large animal model. In this study, for the first time, we systematically investigated the changes in glucose metabolism and cell proliferation signaling pathways in the kidney tissues of chronic progressive PKD mini-pig models created by knock-outing PKD1gene. The results showed that in the kidneys of PKD mini-pigs, the glycolysis is increased and the expressions of key oxidative phosphorylation enzymes Complexes I and IV significantly decreased. The activities of mitochondrial respiration chain Complexes I and IV significantly decreased; the phosphorylation level of key metabolism-modulating molecule AMP-activated protein kinase (AMPK) significantly decreased; and the mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling pathway are activated obviously. This study showed that in the kidneys of PKD mini-pigs, the level of glycolysis significantly increased, oxidative phosphorylation significantly decreased, and cell proliferation signaling pathways significantly activated, suggesting that metabolic changes in PKD may result in the occurrence and development of PKD through the activation of proliferation signaling pathways. [ABSTRACT FROM AUTHOR]

Background: This study compares a traditional parapatellar retinaculum-sacrificing arthrotomy to a retinaculum-sparing arthrotomy in a porcine stifle joint as a cartilage repair model. Findings: Surgical exposure of the femoral trochlea of ten Yucatan pigs stifle joint was performed using either a traditional medial parapatellar approach with retinaculum incision and luxation of the patella ( n = 5) or a minimally invasive (MIS) approach which spared the patellar retinaculum ( n = 5). Both classical and MIS approaches provided adequate access to the trochlea, enabling the creation of cartilage defects without difficulties. Four full thickness, 4 mm circular full-thickness cartilage defects were created in each trochlea. There were no intraoperative complications observed in either surgical approach. All pigs were allowed full weight-bearing and full range of motion immediately postoperatively and were euthanized between 2 and 3 weeks. The traditional approach was associated with increased cartilage wear compared to the MIS approach. Two blinded raters performed gross evaluation of the trochlea cartilage surrounding the defects according to the modified ICRS cartilage injury classification. The traditional approach cartilage received a significantly worse score than the MIS approach group from both scorers (3.2 vs 0.8, p = 0.01 and 2.8 vs 0, p = 0.005 respectively). Conclusion: The MIS approach results in less damage to the trochlear cartilage and faster return to load bearing activities. As an arthrotomy approach in the porcine model, MIS is superior to the traditional approach. [ABSTRACT FROM AUTHOR]

Objective: To observe proliferation and apoptosis of the cell in the kidney of Mini-Pigs with ADPKD.Methods: We observed the protein expression changes of cell proliferation marker PCNA, proliferation-related mTOR signal pathway seed molecules (phospho-mTOR, phospho-p70S6 (Phospho-PKK, phospho-MEK, phospho-ERK), endothelial cell adhesion molecule-1 (CD31), Bax, Bcl-2 and caspase 3 in the kidney tissues of PKD1 Deletion mini-pig model by West-ern blot and immunohistochemical staining.Results: The results showed that the level of PCNA was markedly up-regulated.The molecules in mTOR signal pathway (phospho-mTOR, phospho-p70S6, phospho-4EBP1) ERK signal pathway (phospho-PKA, phospho-MEK, phospho-ERK) and CD3 lwere markedly increased in ADPKD mini-pig kidney tissues. Addition, the Bax / Bcl-2ratio and the caspase3 were increased significantly.Conclusion: The research shown Which the signal pathway of proliferation and apoptosis was activated in ADPKD mini-pig Kidney tissues. [ABSTRACT FROM AUTHOR]

Studied is the sensitivity of different animal species (white mice, rabbits, mini-pigs, and marmots) to Monkeypox virus (MPXV). Determined is the fact that MPXV-sensitive are groundhogs (ID50 and LD50 5 lg of PFU in case of intranasal inoculation). The most pronounced clinical signs of the disease such as varioliform eruption all over body and mucous linings, purulent discharges out of nasal cavity, lymphadenitis, loss of coordination, tremor of extremities, fever, hyper-aggressiveness, disheveled hair have been registered in groundhogs. The highest viral loads in the majority of fallen marmots have been observed in nasal mucosa, trachea, lungs, and pock-marked skin (>6,0 lg PFU/g). The symptomatology of the disease in mice as compared to groundhogs is a bit milder: purulent conjunctivitis, blepharitis, and disheveled hair. As for mini-pigs and rabbits, no visual signs of the disease have been observed in them.

The present study was undertaken to investigate the mechanisms by which Scriptaid treatment improves the developmental competence of somatic cell nuclear transfer (SCNT) mini-pig embryos in vitro. We found that treatment with 500 nmol/L Scriptaid for 15 hours significantly improved the development of mini-pig SCNT embryos. Compared with the control group, the blastocyst rate was higher (18.3% vs. 10.7%; p < 0.05). The acetylation level on H3K14 of the Scriptaid-treated group was higher compared with the control group in SCNT embryos at two-cell, four-cell, and blastocyst stages ( p < 0.05). After Scriptaid treatment, histone deacetylase gene HDAC5 expression level was significantly decreased in four-cell embryos and blastocysts, while the expression levels of the embryos' development-related genes AKT, Oct4, and apoptosis inhibited gene PGC-1α were significantly increased in blastocysts ( p < 0.05). The number of apoptotic cells per blastocyst in the Scriptaid-treated group was lower compared with the control group ( p < 0.05). These results indicate that Scriptaid repressed HDCA5 gene expression, increased the acetylation level of H3K14, upregulated the expression of AKT, Oct4, and PGC-1α genes, improved embryos' development, and reduced apoptosis, which favors development of the SCNT mini-pig embryos to blastocysts. [ABSTRACT FROM AUTHOR]

Curcumin protects the skin against radiation-induced epidermal damage and prevents morphological changes induced by irradiation skin, thereby maintaining the epidermal thickness and cell density of basal layers. In this study, the effects of topical curcumin treatment on radiation burns were evaluated in a mini-pig model. Histological and clinical changes were observed five weeks after radiation exposure to the back (60Co gamma-radiation, 50 Gy). Curcumin was applied topically to irradiated skin (200 mg/cm2) twice a day for 35 days. Curcumin application decreased the epithelial desquamation after irradiation. Additionally, when compared to the vehicle-treated group, the curcumin-treated group showed reduced expression of cyclooxygenase-2 and nuclear factor-kappaB. Furthermore, irradiation prolonged healing of biopsy wounds in the exposed area, whereas curcumin treatment stimulated wound healing. These results suggest that curcumin can improve epithelial cell survival and recovery in the skin and therefore be used to treat radiation burns. [ABSTRACT FROM AUTHOR]

The characterization and potential of mesenchymal stem cells (MSCs) are gender dependent and estrogen influences these properties. This study demonstrated that supplementation with 17β-estradiol (E2) increases the proliferation of bone marrow-MSCs derived from male and female mini-pigs (Mp- and Fp-BMSCs) in a concentration-dependent manner, with 10-12 M E2 suggested as the optimal dose of E2 that led to the greatest improvement in BMSCs proliferation. Supplementation of 10-12 M E2 resulted in down-regulation of β-galactosidase activity and pro-apoptotic activity in both BMSCs, while anti-apoptotic activity was up-regulated in only Fp-BMSCs. Further, E2 increased the osteogenic ability of Fp-BMSCs. Based on these findings, optimal utilization of E2 can improve cellular senescence and apoptosis, as well as in vitro osteogenesis of BMSCs, and could therefore be useful in stem cell therapy, particularly in bone regeneration for adult females. [ABSTRACT FROM AUTHOR]

Microlaryngoscopic enlargement techniques have been the standard treatment for bilateral vocal fold paralysis (BVFP) for decades. Laryngeal pacing is a promising alternative treatment based on the electrostimulation of the posterior cricoarytenoid (PCA) muscle. This paper reports on the results of a pre-clinical study aiming to evaluate this method. Eight Göttingen mini-pigs were implanted with a laryngeal pacemaker (LP) implant prototype and with two LP electrodes, one in each PCA muscle. The 6-week follow-up included endoscopic stimulation controls in general anaesthesia and radiographic controls of electrode integrity and position stability. Stimulation parameters for optimal glottal opening were evaluated via videolaryngoscopy. Histopathology was performed upon conclusion of the study. 7/8 (87.5 %) animals were successfully implanted with the LP implant prototype and two LP electrodes. In general, stimulation was effectively delivered and correlated with the expected PCA muscle activation. 2/14 (14.3 %) electrodes dislocated and 1/14 (7.1 %) electrode tip broke. The LP system used in this experiment to induce vocal fold abduction by means of selective functional electrical stimulation of the PCA showed promising results. It may be a valid alternative to the current golden standard for BVFP treatment. Clinical studies are needed to confirm the medical relevance of the LP. [ABSTRACT FROM AUTHOR]

BACKGROUND: The large animal model of arterial hypertension is very valuable to test the antihypertensive drugs and devices. We characterized a novel swine model of spontaneous hypertension and investigated its response to renal denervation (RDN). METHODS: The blood pressure (BP), levels of plasma catecholamines and urine vanillylmandelic acid, and the protein expressions of angiotensin-converting enzyme (ACE) and angiotensin II type 1 (AT1), and type 2 (AT2) receptors in the rostral ventrolateral medulla (RVLM) were compared between domestic pigs and Guizhou mini-pigs. Twelve-month-old Guizhou mini-pigs were divided into sham (n = 7) and ablation (n = 7) groups. The mini-pigs in ablation group received bilateral percutaneous RDN with a saline-irrigated Sniper ablation catheter. Three months after the procedure, the BP was measured and the histology of renal nerves and arteries was analyzed. RESULTS: The mini-pigs spontaneously developed hypertension by the age of 6 months and the BP (162.2 ± 11.4/111.8 ± 9.2 mm Hg) was significantly higher than age-matched domestic pigs (137.5 ± 1.9/80.2 ± 4.1 mm Hg, P < 0.05). The levels of plasma catecholamines and urine vanillylmandelic acid were higher in mini-pigs than domestic pigs. The expressions of ACE and AT1 were increased, but the AT2 was decreased, in RVLM from mini-pigs compared with domestic pigs. Three months after the procedure, the BP was sharply reduced in ablation group (113.8 ± 14.4/79.4 ± 11.7 mm Hg) compared with sham group (192.4 ± 10.5/141.2 ± 5.9 mm Hg, P < 0.01). Renal nerves were substantially destroyed, while renal arteries and function were not significantly affected by ablation. CONCLUSIONS: The Guizhou mini-pig is a novel spontaneous hypertensive animal model with sympathetic hyperactivity and responds well to RDN. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor binding protein 6 (IGFBP6) is a key factor in regulating the effects of insulin-like growth factor 2 (IGF2) on the animal growth and development, but the mechanism is far from known. In this study, the 5'-terminal sequence of theIGFBP6gene (from −920 to −1 bp) which may regulate gene expression was sequenced in the Bama mini-pigs, the Tibetan mini-pigs, the Landrace pigs, the Large White pigs and the Northeast wild boars to screen for the single nucleotide polymorphisms (SNPs) and analyze the relations with the body size traits of swine through a chi-square test analysis. The genotype frequencies of the SNPs in the 5'-terminal sequence have shown that c.-726C > T, c.-722T > C, c.-535C > A, c.-488T > C, c.-403A > G, and c.-378T > C may be related to the dwarf traits of the Bama mini-pig and the Tibetan mini-pigs (P < .05). A haplotype analysis of the 5'-terminal sequence of theIGFBP6gene in the Landrace pigs, the Large White pigs and the Northeast wild boars found the two SNPs at −403 nt and −378 nt were in linkage and formed three kinds of haplotypes; AT was the dominant haplotype and the haplotype block was not formed in the Bama mini-pigs and Tibetan mini-pigs. Above all, the SNPs and haplotypes of the 5'-terminal sequence of theIGFBP6gene may be involved in the regulation of swine body size. [ABSTRACT FROM AUTHOR]

The present study compared the cellular properties based on cell surface differentiation markers, telomerase activity, stem cell-specific transcripts and differentiation capacity into adipocytes, osteocytes and neurocytes in multipotent mesenchymal stem cells (MSCs) isolated from bone marrow (BMSCs), adipose (ASCs), ovarian (OSCs), muscle (MuSCs) and skin (SSCs) tissues of the same donor mini-pig. Using flow cytometry, all isolated MSCs expressed stem cell-positive surface markers CD29, CD44 and Vimentin, at a high level. Using reverse transcription-polymerase chain reaction, BMSCs, ASCs and SSCs showed higher expression of stem cell-specific transcripts (NANOG, OCT-4 and SOX-2) as compared to OSCs and MuSCs. Telomerase activity was detected by relative-quantitative telomerase repeats amplification protocol at a similar level in all MSCs. Further, analysis of cytochemical staining and lineage-specific transcripts demonstrated that all MSCs get easily differentiated into adipocytes, except for OSCs, whereas, BMSCs and MuSCs easily differentiated into osteocytes, compared to ASCs, OSCs and SSCs. Furthermore, all MSC groups showed the same level of capacity for neurocytes differentiation. Based on these results, the cellular properties were dominantly expressed in BMSCs, ASCs and SSCs, whereas the differentiation capacity was dominantly expressed in BMSCs and MuSCs, compared to others MSCs. Taken together, BMSCs could potentially be used as a good source of MSCs for clinical application and fundamental stem cell research. [ABSTRACT FROM AUTHOR]

Background: To investigate the progression of cartilage degeneration using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping in a mini-pig model of osteoarthritis (OA) caused by anterior cruciate ligament transection (ACLT).Methods: Twelve mini-pigs underwent ACLT in the left knee and were monitored by dGEMRIC (T1, gadolinium [Gd]) and T2 mapping after 2, 4, or 6 weeks (n = 4 each). No ACLT surgery was performed in four healthy control mini-pigs, which were also monitored by dGEMRIC and T2 mapping. Cartilage samples from the weight-bearing regions of the left medial femoral condyles were collected for macroscopic, histological, immunohistochemical, and biochemical analysis. Correlations between biochemical contents and T1,Gd and T2 values were evaluated using Pearson correlation analysis.Results: T1,Gd values were gradually reduced and T2 values increased over time. Cartilage surfaces showed roughness at 4 weeks and additional defects at 6 weeks. Glycosaminoglycan (GAG) distribution and content gradually reduced over time (P < 0.05), and collagen distribution and anisotropy were obviously changed at 6 weeks. However, collagen content did not differ significantly among postoperative timepoints. GAG content was positively related to T1,Gd values (r = 0.888; P < 0.001) and negatively related to T2 values (r = -0.865; P < 0.001). Collagen content had no discernible correlation with T1,Gd or T2 values.Conclusion: dGEMRIC and T2 mapping can monitor the progression of cartilage degeneration in a mini-pig model of ACLT-induced OA, permitting early detection of OA. [ABSTRACT FROM AUTHOR]

To unravel metabolic adaptations preceding the occurrence of metabolic dysregulations, a nutritional challenge appears as the best tool capable to reveal metabolic disturbances compared to single-point measurements at the static fasting (PA) state. The aim of the present work was to study the metabolic trajectories at the postprandial (PP) state in a relevant human nutrition animal model combining plasma metabolome analysis with classical metabolism exploration tools. In a first trial, three mini pigs were fed a test meal and arterial blood samples withdrawn before and over 4 h following the meal for plasma metabolites analysis (LC-MS and classical biochemistry). In a second trial, three mini-pigs were euthanized after an overnight fasting and three others 1:15 h after the test meal. The metabolism was explored at the molecular (mRNA levels), biochemical (enzyme activities) and signalling (phosphorylation status) levels in the liver and muscle. As expected, and in accordance with alterations in plasma glucose, urea levels, gluconeogenesis/glycolysis/lipid and amino acid (AA) oxidation genes expression and enzymes activities, the metabolomic approach discriminated the PA from the PP state (RYcum = 0.991; QYcum = 0.921). More interestingly hierarchical cluster analysis revealed that the PP metabolome included actually four types of kinetic profiles. Further, PLS-DA analysis revealed a two-step pattern: 1-2 and 3-4 h (RYcum = 0.837; Qcum = 0.635). Among the molecules explaining this discrimination, several AAs and phospholipid species were highlighted and their significance in PP metabolism discussed. Our data showed that the combination of these approaches in mini-pigs could be used to investigate PP metabolic adaptations in various physiological and patho-physiological states. [ABSTRACT FROM AUTHOR]

Background: The protein/energy ratio is important for the production performance and utilization of available feed resources by animals. Increased protein consumption by mammals leads to elevated feed costs and increased nitrogen release into the environment. This study aimed to evaluate the effects of dietary protein/energy ratio on the growth performance, carcass traits, meat quality, and plasma metabolites of pigs of different genotypes. Methods: Bama mini-pigs and Landrace pigs were randomly assigned to two dietary treatment groups (Chinese conventional diet with low protein/energy ratio or National Research Council diet with high protein/energy ratio; n = 24 per treatment) in a 2 × 2 factorial arrangement. Blood and muscle samples were collected at the end of the nursery, growing, and finishing phases. Results: We observed significant interactions (P < 0.05) between breed and diet for total fat percentage, intramuscular fat (IMF) content, protein content in biceps femoris (BF) muscle, and plasma urea nitrogen (UN) concentration in the nursery phase; for average daily gain (ADG), average daily feed intake (ADFI), dry matter, IMF content in psoas major (PM) muscle, and plasma total protein and albumin concentrations in the growing phase; and for drip loss and plasma UN concentration in the finishing phase. Breed influenced (P < 0.05) growth performance, carcass traits, and meat quality, but not plasma metabolites. Throughout the trial, Landrace pigs showed significantly higher (P < 0.05) ADG, ADFI, dressing percentage, lean mass rate, and loin-eye area than did Bama mini-pigs, but significantly lower (P < 0.05) feed/gain ratio, fat percentage, backfat thickness, and IMF content. Dietary protein/energy ratio influenced the pH value, chemical composition of BF and PM muscles, and plasma activities of glutamic-pyruvic transaminase and gamma-glutamyl transpeptidase, and plasma concentration of UN. Conclusions: Compared with Landrace pigs, Bama mini-pigs showed slower growth and lower carcass performance, but had better meat quality. Moreover, unlike Landrace pigs, the dietary protein/energy ratio did not affect the growth performance of Bama mini-pigs. These results suggest that, in swine production, low dietary protein/energy ratio may be useful for reducing feed costs and minimizing the adverse effects of ammonia release into the environment. [ABSTRACT FROM AUTHOR]

Objective To investigate the establishment and management of extracorporeal circulation model by mini-pig．Methods After successful anesthesia and tracheal intubation， 12 female mini-pigs were created vascular access of femoral artery and femoral vein．Arterial pressure，heart rate, saturation oxygen，partial pressure of carbon dioxide in end expiratory gas，central venous pressure and packed cell volume were determined before CPB as well as every 1h during CPB．Result The data were within normal limits before and after the establishment of extracorporeal circulation，both of which had no significant difference （P＞0.05）．Conclusion Mini-pig model shows stability in CPB，which can be used for CPB-related research. [ABSTRACT FROM AUTHOR]

The preclinical studies using animal models play a very important role in the evaluation of facial nerve regeneration. Good models need to recapitulate the distance and time for axons to regenerate in humans. Compared with the most used rodent animals, the structure of facial nerve in mini-pigs shares more similarities with humans in microanatomy. To evaluate the feasibility of repairing facial nerve defects by collagen scaffolds combined with ciliary neurotrophic factor (CNTF), 10-mm-long gaps were made in the buccal branch of mini-pigs' facial nerve. Three months after surgery, electrophysiological assessment and histological examination were performed to evaluate facial nerve regeneration. Immunohistochemistry and transmission electron microscope observation showed that collagen scaffolds with collagen binding (CBD)-CNTF could promote better axon regeneration, Schwann cell migration, and remyelination at the site of implant device than using scaffolds alone. Electrophysiological assessment also showed higher recovery rate in the CNTF group. In summary, combination of collagen scaffolds and CBD-CNTF showed promising effects on facial nerve regeneration in mini-pig models. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1669-1676, 2015. [ABSTRACT FROM AUTHOR]

Cloned pigs produced by somatic cell nuclear transfer (SCNT) are important as a potential alternative source of organs. Although SCNT has created new possibilities for targeted gene modification, the successful cloning of pigs is rare. Here, we successfully conducted serial SCNT for three generations. We determined that the piglet genome was inherited from donor cell nuclei using microsatellite analysis of each generation. The methylation of differentially methylated regions (DMRs) inH19was gradually reduced over the three generations of serial SCNT. By contrast, methylation of the insulin-like growth factor 2 (Igf2) DMR increased in the F1 generation, compared to the F0, and remained at the higher level in the F2 and F3 generations. The methylation patterns of housekeeping genes such asGAPDHandβ-actinwere unchanged in the serially cloned pigs. In addition, expression levels ofH19andIgf2were variable for each generation of serial SCNT piglets, but there was no clear relationship between the methylation and gene expression patterns. Our study conclusively demonstrates that the methylation patterns of DMRs inH19andIgf2were altered, compare to the F0 donor, during serial SCNT, but housekeeping genes were unaffected. [ABSTRACT FROM PUBLISHER]

To investigate the effects of QuTan HuaYu TongMai granule (QHTG) on the perturbed metabolism of atherosclerosis mini-pig model, a serum metabonomics method based on Liquid chromatography/mass spectrometry was developed. Principal component analysis and partial least squares-discriminate analysis models were established for the metabonomics analysis. The effect of high dose QHTG group is equivalent with those of positive drugs group in PCA score plots. Some significantly changed metabolites, including lyso-PCs, metabolites of vitamin D and fatty acids were found to be reasonable in explaining the anti-atherosclerosis mechanism of QHTG. Metabonomic approach is helpful to further understand the pathophysiology of atherosclerosis in mini-pigs and the therapeutic mechanism of QHTG. Our work also indicated that the LC-MS based metabonomics method is a potential tool for performing intervention and mechanism research of traditional Chinese medicine (TCM). [ABSTRACT FROM AUTHOR]

In this study, serum metabolic profiles of mini-pigs with atherosclerosis (AS) were analyzed by LC-TOFMS. Partial least-squares to latent structure-discriminant analysis and orthogonal projection to latent structure-discriminant analysis were used for group differentiation and selection of potential biomarkers. The mini-pig disease models were constructed by feeding a high-fat diet and inducing coronary injury, in accordance with the mechanism of AS pathogenesis. To characterize the development of AS, serum samples were collected and analyzed at two time points (two and ten weeks). Separate distinct clustering of results from normal and model mini-pigs could be observed for both the two and ten-week samples. With the development of AS, the metabolism of the model mini-pigs was more substantially disturbed. Major metabolites contributing to the discrimination were fatty acids, lysophosphatidylcholines, and bile acids. These potential biomarkers are related with inflammation, oxidative stress, and abnormal lipid and energy metabolism. [ABSTRACT FROM AUTHOR]

Selenoprotein S (SelS), a member of selenoprotein family, plays important regulatory function in inflammation and metabolic diseases. SelS expression is up-regulated response to the inflammatory stimulus in many mammal cells, animal models as well as patients. In order to further understand the function of SelS gene, molecular characterization and transcriptional regulation of SelS from a Bama mini-pig were analyzed in the present study. The results showed that pig SelS encoded a protein of 190 amino acid with estimated molecular weight of 21.23 kDa and pI of 9.526. The genomic structure, promoter and deduced amino acid sequence were analyzed and found to share high similarity with those of human SelS. Pig SelS fusion protein was demonstrated to localize in the cytoplasm by fluorescence microscopy. Real-time PCR revealed the ubiquitous expression pattern of pig SelS in diverse tissues, a high level expression was observed in the liver and lung, relatively low expression in other tissues, especially in muscle. Promoter deletion analysis further suggests that an NF-κB binding site within the SelS promoter is responsible for the up-regulation of SelS transcription. [ABSTRACT FROM AUTHOR]

Abstract: The use of platelet-rich plasma (PRP) for improving of bone defect healing is discussed controversially. The aim of this study was to assess the effect of PRP in combination with autologous cancellous graft on bone defect healing in a critical metaphyseal long bone defect. A critical size defect in the tibial metaphysis of 16 mini-pigs was filled either with autologous cancellous graft as control group or with autologous cancellous graft combined with autologous PRP. Compared to native blood platelets were enriched about 4.9-fold in the PRP. After 6 weeks, the specimens were assessed by X-ray and histological evaluation. Histomorphometrical analysis revealed that the area of new bone was significantly higher in the PRP group concerning the central area of the defect zone (p <0.02) as well as the cortical defect zone (p <0.01). All defects showed substantial new bone formation, but only defects of the PRP group regenerated entirely. The PRP group was superior to the control group even in the semi-quantitative assessment of the osseous bridging in both observed areas of the defect. Within the limits of the present study it could be demonstrated that PRP combined with autologous cancellous graft leads to a significantly better bone regeneration compared to isolated application of autologous cancellous graft in an in vivo critical size defect on load-bearing long bones of mini-pigs. [Copyright &y& Elsevier]

Abstract: Transmissible gastroenteritis virus (TGEV) is the causative agent of porcine transmissible gastroenteritis (TGE), characterized by high mortality and severely retarded growth in piglets that dramatically affects the porcine industry. Previously, we have identified two shRNA-expressing plasmids pEGFP-U6/P1 and pEGFP-U6/P2 that target RNA-dependent RNA polymerase (RdRP) gene of TGEV with more than 95% of virus inhibition in vitro. In this study, inhibition of the TGEV replication by pEGFP-U6/P1 and pEGFP-U6/P2 was tested in mini-pigs. SPF mini-pigs at 25 days old were injected with the shRNA-expressing plasmids and then infected with TGEV. The results from the analyses of clinical signs, histopathology, indirect immunofluorescence (IIF) and RT-PCR show that the two shRNA-expressing plasmids could significantly decrease the quantity of TGEV in different organs and protect mini-pigs from TGEV infection. These findings illustrate the prospect for TGEV-specific shRNAs to be new anti-TGEV agents. [Copyright &y& Elsevier]

Abstract: Volatiles from roasted pork of Mini-pig were first investigated by solid phase microextraction (SPME) as well as simultaneous distillation and solvent extraction (SDE) combined with gas chromatography and mass spectrometry (GC–MS). Total of 86 different compounds were identified with aldehydes being the most abundant followed by the spice components such as estragole, trans-anethole, eugenol and so on. Compared with other cooked meat products, much low amount of aliphatic alcohols were present in the roasted Mini-pig pork. The SDE isolation was preferred in the characterization of meat flavor considering that semi-quantitative data was conveniently obtained, more components were revealed, artifact formation was limited and aromatic profile was representative of the meat sample. By gas chromatography and olfactometry (GC–O), 45 olfactory regions were exposed and 43 flavors were located. Finally, 17 important flavor substances in the SDE extract were quantified by gas chromatography and flame ionization detector (GC–FID) using calibration curves of authentic chemicals. [Copyright &y& Elsevier]

Volatile composition of Chinese traditional smoke-cured bacon of Mini-pig breed was first characterized. Both headspace solid phase microextraction (SPME) and simultaneous distillation and solvent extraction (SDE) were performed. SDE exhibited efficiency in the extraction of representative aromatic volatiles especially the phenolic smoky flavors from the bacon sample. In total, 104 different components were found with the major quantity and kinds of aromas being the volatile saturated and unsaturated aldehydes from lipid oxidation and the phenolic compounds from smoke. Olfactory evaluation (GC-O) of the SDE extract revealed five basic odor patterns pertaining to 53 odor active regions and 47 odorants. Some key flavors accounting for the bacon aroma were (E, E)-2, 4-decadienal, 3-(methylthio) propanal, 2-furanmethanol, guaiacol, 3-ethylphenol and 2, 5-dimethylpyrazine. [ABSTRACT FROM AUTHOR]

The present study describes the occurrence of abnormal mitochondria in the cytoplasm of hepatocytes from half-term mini-pig fetuses, whose mothers in addition to their ordinary fodder have received alcohol (ethanol) in daily amounts comparable to those consumed by human alcoholics. The abnormal mitochondria exhibit elongation and distortion, disorientation of cristae and the appearance of paracrystalline and electron-dense material in the matrix. These ultrastructural changes show striking similarities to the mitochondrial injuries seen initially in the hepatocytes of human alcoholics and probably reflect damage to the mitochondria caused by alcohol itself. [ABSTRACT FROM AUTHOR]

Endoscopic correction of vesicoureteric reflux by subureteric injection has become an accepted method of treatment in selected cases. Its efficacy has been demonstrated in the treatment of well over 1,000 ureters. However, there are doubts as to the long-term safety of the commonly injected substance Teflon. Glutaraldehyde cross-linked bovine collagen, a biodegradable substance, was suggested as an alternative material for injection. The aim of this study was to evaluate the histological long-term behavior of glutaraldehyde cross-linked bovine collagen injected into the mini-pig bladder. One hundred and eight deposits of cross-linked collagen, each containing 0.2 ml ( n = 36) or 0.6 ml ( n = 72) collagen paste, were injected into the suburothelial space of the bladders of 24 mini-pigs. The histological behavior of the implants was studied at monthly intervals over a period of 12 months. After only 2 months a marked invasion of host fibroblasts and formation of endogenous type I and III collagen could be observed. Over 12 months the invasion of fibroblasts and the formation of new collagen increased dramatically. No migration of collagen particles into the local lymphatic system could be observed. A new staining technique (solophenyl red 3BL) was introduced to selectively demonstrate type I and III collagen fibres. In addition, the efficacy of the subureteric collagen injections could be demonstrated by successfully treating reflux that was iatrogenically induced in the mini-pig bladders. [ABSTRACT FROM AUTHOR]

Electron microscopic investigations of secretory ameloblasts from deciduous tooth germs of mini-pig foetuses and investigations of the ability of various fixatives to preserve these cells in tooth germs immersion-fixed in toto 5 min, 10 min, 15 min, 20 min and 40 min after death of the mother gave the following results: [ABSTRACT FROM AUTHOR]

The influence of hyper- and hypothyroidism on atrial and ventricular myosin structure and Ca-activated ATPase activity has been analyzed in adult mini-pigs. Whereas no difference could be demonstrated between hypo- and euthyroid ventricular myocardium, Ca-activated ATPase activity was significantly higher in the hyperthyroid than in the hypo- or euthyroid state. Using pyrophosphate electrophoresis and isoelectric focusing of subfragment 1 this could be ascribed to an additional ventricular myosin in the hyperthyroid myocardium. Atrial myosin ATPase activity and structure were not influenced by the thyroid state of the animals. These results present evidence that thyreotoxicosis induces an additional isomyosin in the pig ventricular myocardium, albeit to a lesser degree than in the rodent heart. The lacking difference between the hypothyroid and the euthyroid states indicates that a myosin with a lower enzymatic activity than the normal ventricular myosin is not synthesized in the heart of higher mammals. [ABSTRACT FROM AUTHOR]

The vasodilator and inotrapic actions of amrinone were investigated in mine-pigs under pentobarbitone anaesthesia. Left ventriculat volume was determined angiocardiographically under afterloaded and isovolumetric conditions. Furthermore, aortic flow, left ventricular pressure and aortic pressure were measured. In some of the animals, the β-adrenergic receptors were blocked with propranolol prior to the administration of amrinone. Without blockade of the β-receptors, amrinone (2 mg kg ) caused a significant reduction in mean aortic pressure. Due to less end-diastolic ventricular filling, stroke volume decreased, and thus ejection fraction remained constant. Since heart rate increased under amrinone, cardiac output remained constant. At the same time, the maximum rate of pressure rise increased, despite less end-diastolic ventricular filling. Sfter blockade of the β-adrenergic receptors, aortic pressure, end-diastolic ventricular filling, and stroke volume also decreased with amrinone. In contrast, heart rate remained practically constant, so that cardiac output declined. The maximum rate of pressure rise also declined due to less end-diastolic ventricular filling. It can be concluded from these results that, in situ, the primary action of amrinone occurs on vascular smooth muscle and that a positive inotropic activity with a normal dosage of amrinone is only an indirect outcome of reflex activation of the sympathetic system. Analysis of isovolumetric mechanograms and the ejection phase does not indicate a direct positive inotropic effect of amrinion. In the failing heart, however, beneficial effects can be expected, since the maxima curves follow a flatter course. Thus a reduction in afterload can lead to a significant increase in stoke volume, provided that aortic pressure does not fall below the critical coronary perfusion pressure. [ABSTRACT FROM PUBLISHER]

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