Non-injected Group Research Articles

Prevalence of hepatitis C virus infection among HIV+ men who have sex with men: a systematic review and meta-analysis.

Since 2000, an increase in hepatitis C virus infection among HIV-infected (HIV+) men who have sex with men has been observed. Evidence points to blood exposure during sex as the medium of hepatitis C virus transmission. Hepatitis C virus prevalence among HIV + MSM overall and in relation to injection drug use is poorly characterized. In this study, a systematic review and meta-analysis examining global hepatitis C virus antibody prevalence and estimating active hepatitis C virus prevalence among HIV + MSM were conducted; 42 reports provided anti-hepatitis C virus prevalence data among HIV + MSM. Pooled prevalence produced an overall anti-hepatitis C virus prevalence among HIV + MSM of 8.1%; active HCV prevalence estimate was 5.3%-7.3%. Anti-hepatitis C virus prevalence among injection drug use and non-injection drug use HIV + MSM was 40.0% and 6.7%, respectively. Among HIV + MSM, hepatitis C virus prevalence increased significantly over time among the overall and non-injection drug use groups, and decreased significantly among injection drug use HIV + MSM. We identified a moderate prevalence of hepatitis C virus among all HIV + MSM and among non-injection drug use HIV + MSM; for both, prevalence was observed to be increasing slightly. Pooled prevalence of hepatitis C virus among HIV + MSM was higher than that observed in the 1945-1965 US birth cohort. The modest but rising hepatitis C virus prevalence among HIV + MSM suggests an opportunity to control HCV among HIV + MSM; this combined with data demonstrating a rising hepatitis C virus incidence highlights the temporal urgency to do so.

Low-level laser therapy stimulates tissue repair and reduces the extracellular matrix degradation in rats with induced arthritis in the temporomandibular joint.

The objective of this study was to characterize morphological and biochemistry action of low-level laser therapy (LLLT) on induced arthritis in the temporomandibular joint (TMJ) of rats. Twenty-four male Wistar rats were randomly divided into groups with 12 animals each: (AG) group with arthritis induced in the left TMJ and (LG) group with arthritis induced in the left TMJ and treated with LLLT (830nm, 30mW, 3 J/cm(2)). Right TMJs in the AG group were used as noninjected control group (CG). Arthritis was induced by intra-articular injection of 50μl Complete Freund's Adjuvant (CFA) and LLLT began 1week after arthritis induction. Histopathological analysis was performed using sections stained with hematoxylin-eosin, Toluidine Blue, and picrosirius. Biochemical analysis was determined by the total concentration of sulfated glycosaminoglycans (GAGs) and evaluation of matrix metalloproteinases (MMP-2 and MMP-9). Statistical analysis was performed using paired and unpaired t tests, with p < 0.05. Compared to AG, LG had minor histopathological changes in the TMJ, smaller thickness of the articular disc in the anterior (p < 0.0001), middle (p < 0.0001) and posterior regions (p < 0.0001), high birefringence of collagen fibers in the anterior (p < 0.0001), middle (p < 0.0001) and posterior regions (p < 0.0001) on the articular disc, and statistically lower activity of MMP-2 latent (p < 0.0001), MMP-2 active (P = 0.02), MMP-9 latent (p < 0.0001), and MMP-9 active (p < 0.0001). These results suggest that LLLT can increase the remodeling and enhancing tissue repair in TMJ with induced arthritis.

Preoperative Hip Injections Increase the Rate of Periprosthetic Infection After Total Hip Arthroplasty

BackgroundIntraarticular injections are both diagnostic and therapeutic for patients with osteoarthritis. A potential risk of periprosthetic joint infection (PJI) after total hip arthroplasty (THA) may occur from direct inoculation and/or immune suppression by corticosteroids. Large population-level databases were used to evaluate hip injection on the 1-year rate of PJI in patients undergoing primary THA. MethodsState-level ambulatory surgery and inpatient databases for Florida and California (2005-2012) were used to identify primary THA patients with 1-year preoperative and postoperative windows to evaluate possible injections or PJI, respectively. Patients were grouped as no injection or as THA performed 6-12 months, 3-6 months, or 0-3 months after injection. Risk adjustment was performed with multivariable regression. ResultsA total of 173,958 patients were included; 5421 (3.1%) underwent THA after an injection: 1395 (1.1%) of patients after 6-12 months, 1863 patients after 3-6 months, and 2163 (1.2%) after 0-3 months. In the 0-3 month group, PJI was significantly increased at 3 months (1.58%, P = .015), 6 months (1.76%, P = .022), and 1 year (2.04%, P = .031) compared with the noninjection control group (1.04%, 1.21%, and 1.47%, respectively). There were no differences in the 3- to 6-month and 6- to 12-month injection groups. ConclusionThere is an increased risk of PJI when THA is performed within 3 months of hip injection. We recommend that patients and their surgeons consider delaying elective THA until 3 months after an injection to avoid this elevated risk of infection.

Adipose stromal cells improve healing of vocal fold scar: Morphological and functional evidences.

Adipose derived stromal cells (ASCs) are abundant and easy to prepare. Such cells may be useful for treating severe vocal disturbance caused by acute vocal fold scars. Prospective animal experiments with controls. Twenty New-Zealand white rabbits were used in the present study. We evaluated vocal fold healing, with or without injection of autologous ASCs, after acute scarring. A defined lesion was created and the ASCs were immediately injected. Vocal fold regeneration was evaluated histomorphometrically and via viscoelastic analysis using an electrodynamic shaker. Six weeks after ASC injection, vocal folds exhibited significantly less inflammation than control folds (P < 0.005). In addition, hypertrophy of the lamina propria and fibrosis were significantly reduced upon ASC injection (P < 0.02). The decrease in viscoelastic parameters was less important in the ASC injected group compared to the noninjected group (P = 0.08). Injection of autologous ASCs improved vocal fold healing in our preclinical model. Further studies are needed, but this method may be useful in humans. NA. Laryngoscope, 126:E278-E285, 2016.

Triphenyltin induces imposex in Nucella lapillus through an aphallic route

Triphenyltin (TPT) was used until recently as a biocide in antifouling systems and nowadays is still applied as an agriculture pesticide in some countries. This compound is known to cause imposex (the imposition of male characters in females of gastropod molluscs) in a very limited number of species, when compared with tributyltin (TBT), the universally recognized imposex-causing agent. In this study, we tested if TPT could induce imposex in females of the dog-whelk Nucella lapillus. Experimental groups of 40 females were injected with a volume of 2μL/g of soft tissue wet weight (ww) of one of the following treatments, using DMSO as a solvent carrier: DMSO (solvent control); 1μg/g ww of TBT (positive control); 0.2, 1 and 5μg/g ww of TPT and a non-injected group (negative control). Concentrations were confirmed in the organism tissues by means of chemical analyses of a pool of 10 specimens at T0 and then after the imposex analysis at T56days. After 8-week trial, results pointed out statistically significant differences between treatments, with both TPT and TBT positively inducing imposex. However, imposex development in TPT-injected females differed from that of TBT, since females that developed imposex presented an aphallic condition (no penis development) while the TBT-treated females developed standard imposex (with penis formation). These results suggest that TPT and TBT act differently in the sequential process of female masculinization, casting new insights about the hypothetical pathways underlying imposex development.

240 PRECISE GENOME EDITING OF PDX1 BY DIRECT INJECTION OF TRANSCRIPTION ACTIVATOR-LIKE EFFECTOR NUCLEASES (TALENS) INTO PARTHENOGENETIC PIG EMBRYOS

Pancreatic and duodenal homeobox 1 (PDX1) is one of the transcription factors involved in pancreatic organogenesis and plays a critical role as an early lineage marker of pancreatic specification and β-cell differentiation. In mature pancreas, PDX1 regulates a large number of genes involved in maintaining β-cell identity and function. In mice and humans, its homozygous disruption results in pancreas agenesis, while heterozygous mutations have been associated with early-onset (MODY) and late-onset forms of Type II diabetes mellitus in humans. Knockout of the PDX1 gene in pigs may lead to the generation of an apancreatic phenotype, which in turn could allow the potential generation of an exogenic pancreas. Moreover, this could help to create a large animal model for human diabetes. We used transcription activator-like effector nucleases (TALEN) technology with the aim of studying the efficiency of precise editing by homologous recombination in parthenogenetically activated porcine embryos. Mature oocytes were activated by incubation in ionomycin (10 µM) for 20 min, followed by a 4-h incubation in DMAP (2 mM) + cytochalasin B (7.5 µg mL–1). Cytoplasmic injection was performed 14 h post-activation. Post injections, embryos were cultured for 6 days in NCSU23+BSA media at 38.5°C in a 5% CO2 atmosphere. We first evaluated the activity of a pair of TALENs targeting the functional domain of the PDX1 gene. Three concentrations of mRNA were microinjected (10, 20, and 40 ng µL–1) and blastocysts were analysed for non-homologous end-joining (NHEJ) by sequencing. The efficiency of indel mutations at the PDX1-target loci (either monoallelic or biallelic) was 34.5, 52.6, and 80.0% for the 10, 20, and 40 ng µL–1 concentrations, respectively. Next, we tested whether ssODNs (single-stranded oligodeoxynucleotide) coinjected with TALENs would permit precise homology direct repair (HDR) in porcine parthenotes. TALEN mRNA (40 ng µL–1) was coinjected with an ssODN donor template (50 ng µL–1) designed to incorporate a novel stop codon, HindIII restriction site, and a frame shift mutation. Cleavage and blastocyst rates were recorded at Days 2 and 6 of development, respectively, in the TALEN/ssODN injected group (n = 260 zygotes), buffer-injected embryos (n = 135 zygotes), and the non-injected group (n = 132 zygotes). Day 7 embryos were analysed for NHEJ and HDR by RFLP assay and Sanger sequencing after whole-genome amplification and PCR. Blastocyst rates were 15% (TALEN/ssODN-injected group), 27% (buffer-injected group), and 34% (non-injected group). A total of 30 blastocysts were analysed for HDR after whole-genome amplification. The majority of analysed blastocysts (28/30, 93%) were mutant. Among them, 10 (36%) incorporated the ssODN, from which 3 (30%) showed a KO genotype with a precise biallelic modification. We report here a highly efficient and precise TALEN-mediated gene knockout in swine embryos, which represents an alternative to cloning for phenotype evaluation of knockouts related to organogenesis.

Effects of in ovo injection of organic trace minerals and post-hatch holding time on broiler performance and bone characteristics

Effects of the in ovo injection of organic Mn, Zn, and Cu in association with post-hatch (POH) feed and water restriction on the performance and physical-chemical bone parameters of male Ross × Ross 708 broilers were examined. On 17 d of incubation, a total of 1,872 eggs were subjected to in ovo injection using a commercial multi-egg injector. Treatments (TRT) includingd non-injected and diluent-injected controls. The respective Zn, Mn, and Cu levels (mg/mL) added to the diluent of the low (LMD) and high mineral (HMD) TRT groups were 0.181, 0.087, and 0.010, and 0.544, 0.260, and 0.030, respectively. The 4 TRT groups were then sub-divided into 2 POH holding time (HT) groups, with 15 birds randomly allocated to each of 6 replicate pens in each of the 8 groups. The first HT group (0HT) had immediate access to water and feed, and the second HT group (24HT) contained birds that were kept in transport baskets for 24 h before being released. Performance was determined and selected birds were subsequently necropsied and their tibiae extracted for analysis. In comparison to birds from 24HT group, those in the 0HT group had a higher BW gain and feed intake, and a lower FCR through 21 d POH. The percentage of bone ash of the birds belonging to the HMD group was higher than all other TRT on d 1 POH and was higher than the non-injection control group on d 21 POH. On d 1, the LMD and HMD groups had higher tibial Mn concentrations than those of the control groups. On d 7, bones from the HMD group had a higher concentration of Mn than did the non-injected control group, and likewise, on d 21 POH, had a higher concentration of Zn than did the control groups. In conclusion, a 24HT negatively affected the performance of the birds during the first 2 wk POH; however, the LMD and HMD TRT had a positive influence on bone mineralization.

Effects of in ovo injection of organic zinc, manganese, and copper on the hatchability and bone parameters of broiler hatchlings

Effects of the in ovo injection of commercial diluent containing supplemental microminerals (Zn, Mn, and Cu) on hatchability and hatching chick quality variables in Ross × Ross 708 broilers were examined. On 17 d of incubation (doi) eggs were subjected to 1 of 4 treatments using a commercial multi-egg injector. Treatments included non-injected (treatment 1) and diluent-injected (treatment 2) control groups. Those in treatment 3 received diluent containing 0.181, 0.087, and 0.010 mg/mL of Zn, Mn, and Cu, respectively, and those in treatment 4 received diluent containing 0.544, 0.260, and 0.030 mg/mL of Zn, Mn, and Cu, respectively. A total of 1,872 eggs were distributed among 4 treatment groups on each of 6 replicate tray levels. Hatchability of fertile eggs set (HF) was determined on 20.5 and 21.5 doi. On 21.5 doi, HF and mean hatching chick weight (MHW) were determined. One bird from each treatment replicate group was randomly selected, weighed, and necropsied for the extraction of their livers and tibiae. The tibiae fresh and dry weight, length, width, bone breaking strength (BBS), and percentage of bone ash (PBA) were determined. The dry livers were weighed and ashed. Injection treatment had no significant effect on HF at 20.5 doi. However, there was a significant injection treatment effect on HF at 21.5 doi. The HF of eggs at 21.5 doi in treatment 4 was significantly lower than that of the non-injected control group, with treatment 3 being intermediate. Furthermore, there were no significant treatment effects noted for MHW fresh and dry tibia weights, tibia length and width, tibia length to weight ratio, BBS, liver ash content, or percentage of minerals (Ca, P, Mg, Mn, and Zn) in the tibia ash. However, embryos from eggs that received treatment 4 had a significantly higher PBA in comparison to all other treatments. In conclusion, although treatment 4 negatively affected HF, the injection of diluent containing the high micromineral concentration has the potential to improve bone mineralization.

Preoperative epidural spinal injections increase the risk of surgical wound complications but do not affect overall complication risk or patient-perceived outcomes.

OBJECT A lack of information exists on the relationship between preoperative epidural spinal injections and outcomes after spine surgery. There is concern that injections might cause local changes, increasing the infection risk and surgical difficulty. Therefore, the authors explored the relationship between preoperative spinal injections and postoperative outcome. METHODS The cohort was comprised of patients who underwent thoracic and/or lumbar arthrodesis during the years 2007-2010 and had complete (preoperatively and 3 months postoperatively) outcome scores. Patients' clinical courses were reviewed to determine the occurrence of major complications within a 30-day postoperative period. Patient-perceived outcomes were evaluated using the Oswestry Disability Index (ODI) and the SF-12 (12-Item Short Form Health Survey): mental component summary (MCS) and physical component summary (PCS) scores. Analyses were based on exposure to injections and were performed using chi-square exact tests and paired and unpaired t-tests. RESULTS Two hundred eighty patients met the inclusion criteria: 117 patients (41.8%) received and 163 patients (58.2%) did not receive preoperative epidural spinal injections. Overall, the likelihood of complication did not differ with respect to exposure (13.7% injection vs 11.7% noninjection); however, injected patients observed a 7.4-fold risk of developing surgical wound complications over noninjected patients (5.1% vs 0.6%, p = 0.02). Patient-perceived outcomes measures demonstrated no differences between groups. Three months postoperatively, the MCS and ODI scores were similar (MCS: 49.6 ± 11.6 injection vs 47.4 ± 12.8 noninjection; ODI: 35.8 ± 18.0 vs 34.4 ± 19.1). MCS or ODI score improvement (preoperatively compared with 3 months postoperatively) did not vary between groups. Injected patients maintained a 2-point lower PCS score at entry and 3 months postoperatively as compared with noninjected peers (entry: 27.6 ± 8.2 injection vs 29.5 ± 9.3 noninjection, p = 0.09; 3 months: 33.3 ± 8.6 vs 35.7 ± 9.0, p = 0.03); the PCS score improvements between injected and noninjected groups were similar (5.7 ± 9.9 vs 6.2 ± 9.7). CONCLUSIONS Patients exposed to preoperative epidural injections had similar complication rates to those who never received a spinal injection. However, they had a greater risk of developing wound complications. These complications had no effect on short-term improvements in outcome measures.

Longitudinal assessment of bone loss using quantitative ultrasound in a blood-induced arthritis rabbit model.

Osteoporosis is common in haemophilic arthropathy. Quantitative ultrasound (QUS) can be a suitable alternative for dual-energy x-ray absorptiometry for diagnosing osteoporosis in haemophiliacs due to its lack of ionizing radiation, and ease to use. We investigated the intra- and inter-operator reliability of QUS, its responsiveness to bone growth, its ability to differentiate bone adjacent to blood-injected vs. control joints, and the effect of soft tissues on the speed of sound (SOS) QUS values in a juvenile white New Zealand rabbit model of blood-induced arthritis. Eight of 16 rabbits were injected with autologous blood (0.1 mL kg(-1) ) 8 times over a 17-week period, the remaining eight rabbits served as controls. SOS was measured at baseline, weeks 8 and 17 in vivo and after the bones were excised on week 17. Intra- and inter-operator coefficients of variation for QUS data were <5% and intraclass correlation coefficients were >60% for 22/27 (81.5%) of bones assessed. The level of interval increase in SOS values from baseline to week 17 was significantly different in tibiae of injected, contralateral to injected and non-injected knee groups by anova (P = 0.01). In vivo (mean ± SD, 4147.17 ± 96.27 m s(-1) ) and postmortem (4457.85 ± 104.00 m s(-1) ) measurements on week 17 differed (P < 0.01) indicating an effect of soft tissues on SOS. In conclusion, QUS' acceptable reliability, its responsiveness to growth-related changes and its ability to discriminate injected and non-injected joints make this technique a plausible candidate as a diagnostic tool for osteoporosis in the paediatric haemophilic population if these results are confirmed upon animal-human translation.

Adipose-Derived Stem Cells Improve Survival of Random Pattern Cutaneous Flaps in Radiation Damaged Skin.

Tissue ischemia and necrosis following surgery after radiotherapy on the skin and subcutaneous tissue are well known to all reconstructive surgeons. Nevertheless, there has been no report so far on local effects of adipose-derived stem cells (ADSCs) on random flap survival elevated in an irradiated rat dorsum. In this experimental study, we aimed to identify the effect of adipose tissue-derived stem cell injection on random flap survival in irradiated tissues. Adipose-derived stem cells were isolated from the groin region of Sprague-Dawley rats and expanded ex vivo for 3 passages. Animals were divided into 2: irradiated and nonirradiated and then again into ADSC injected and noninjected groups altogether 4 groups. After elevation of caudally based dorsal random skin flaps (10 cm long and 3 cm wide), Green fluorescent protein labeled ADSCs were then injected to the base of the pedicle. Radiotherapy was 20 Gy single dose applied during 8 weeks before surgery. At postoperative day 7, flap viability measurement and tissue harvest for histologic and immunocytochemical assessment were performed in all groups. We have observed increased flap viability in ADSCs injected irradiated group compared with control radiation group with small but not statistically significantly increase in vessel count per field. Mean survival rate of the flaps in groups A, B, C, and D were 40.46%, 60.07%, 40.90%, and 56.13%, respectively. There was a statistically significant vessel count difference between group B and group A and also with group D (P < 0.001). These findings suggest that ADSCs have a potential for enhancing the blood supply of random pattern skin flaps after radiation injury. This mechanism might be both neovascularization and vasodilation along with endothelial repair. Further studies are needed.

Measuring task performance after acquired brain injury: Construct and concurrent validity of ‘Upper Limb Performance Analysis’

Objective: This preliminary investigation studies selected aspects of validity of the Upper Limb Performance Analysis (ULPA), an occupation-based functional upper limb (UL) measure.Methods: The study investigated the ULPA–Task Performance Mastery (ULPA-TPM) in 35 community dwelling adults with upper motor neuron syndrome following acquired brain injury and 26 healthy controls. Construct and concurrent validity of the ULPA were determined via group discrimination between adults with and without ABI; and ABI participants who were and were not referred for UL spasticity management with botulinum toxin-A injections (injected and non-injected group). Concurrent validity was examined by investigating the relationships between the ULPA and an existing functional UL measure, the Action Research Arm Test, using Spearman’s rank-order correlation.Results: Significant differences in UL performance were demonstrated between the ABI and the Control group on all ULPA sub-scales (including: Omission (z = −2.6 to −3.6, rspb = 0.37–0.48), Accuracy (z = −5.8 to −6.0, rspb = 0.78–0.82), Repetition (z = −5.1 to −5.4, rspb = 0.63–0.73) and Timing errors (z = −5.9 to −6.2, rspb = 0.77–0.88). Those in the Injected group demonstrated more task performance errors than the Non-injected group, with significant differences in Accuracy (z = −2.1 to −2.4, rspb = 0.37–0.45), Repetition (z = −2.5 to −2.1, rspb = 0.43) and Timing (z = −2.0, rspb = 0.37).Conclusions: This study demonstrated good construct and concurrent validity of the ULPA-TPM.

Sa1524 Identification of Esophago-Gastric Junction During Per-Oral Endoscopic Myotomy-Benefit of Indocyanine Green Injection

Sa1524 Identification of Esophago-Gastric Junction During Per-Oral Endoscopic Myotomy-Benefit of Indocyanine Green Injection

Clinical and MRI outcomes of HA injection following arthroscopic microfracture for osteochondral lesions of the talus.

The purpose of this study was to compare the clinical and magnetic resonance imaging (MRI) outcomes of arthroscopic microfracture surgery alone or in combination with hyaluronic acid (HA) injection in the treatment of osteochondral lesions of the talus. Thirty-five patients with osteochondral lesions of the talus who underwent arthroscopic microfracture were included and followed up for at least 9months post-operatively. The patients were randomly divided into non-injection group (n=17) who received treatment with microfracture surgery alone and injection group (n=18) who also accepted intra-articular injection of HA post-operatively. Quantitative MRI was used to evaluate the cartilage repair after surgery. American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hind foot Scale scores and Visual Analogue Scale (VAS) scores were used to evaluate clinical outcomes. After operation, the MRI outcomes showed that the thickness index was higher (0.8±0.1 vs. 0.7±0.1) and the T2 index was lower (1.2±0.1 vs. 1.4±0.1) in the injection group than in the non-injection group (P<0.01). As for the volumes of subchondral bone marrow oedema, there are no significant differences between groups (n.s.). Compared with the non-injection group, the AOFAS score and the VAS score yielded a higher level of improvement in injection group at final follow-up post-operatively (P<0.05). Arthroscopic microfracture is a safe and effective procedure for osteochondral lesions of the talus. Intra-articular HA injection as an adjunct to arthroscopic microfracture might offer better functional recovery than microfracture alone. II.

Effects of small dose estradiol cypionate after artificial insemination on reproductive performance in Holstein cows

The goals of this study were to assess whether the injection of 1 mg of estradiol cypionate (ECP) at 13 days after service of artificial insemination (AI) increases fertility in the study subject and if the same dose injected in the near estrus (20 ± 1 days) after artificial insemination services changed the diagnosis in empty cows without affecting the ongoing gestation. Two experiments were conducted with Holstein cows: (1) In the first experiment, 110 animals were used in summer season and were inseminated and divided randomly in injected and non-injected groups (n = 55). At 13 days post-service, animals in injected group received intramuscularly 1 mg of ECP. (2) The other experiment was conducted during both summer and winter. Four hundred lactating Holstein cows were selected from first and second services. The pregnancy diagnosis were performed by rectal palpation on day 43, only in cows that had not repeated the artificial insemination. The injection of 1 mg ECP at 13 days after IA service does not affect ongoing pregnancy and increases fertility (p < 0.05). In Holstein cows that repeated the heat due the treatment, decreased significantly the proportion of cows that arrive empty to the diagnosis during the summer but not in winter.

Effects of dopaminergic agents on progression of naturally occurring myopia in albino guinea pigs (Cavia porcellus).

Disruption of dopaminergic signaling has been implicated in the abnormalities of ocular development in albinism, and many experiments have shown that retinal dopamine is a major regulator of postnatal eye growth and myopia in animal models. Therefore, in the present study we investigated whether progressive myopia, which can occur in albino guinea pigs without experimental manipulation of visual conditions, is affected by dopaminergic agents. Two-week-old albino guinea pigs, selected for being myopic (range refractive error [RE], -2 to -10 diopters [D]), received unilateral peribulbar injections of apomorphine (nonselective dopamine receptor agonist; 0, 7.5, 25, 75, 250, 750, and 2500 ng; n = 112), SKF38393 (D1-like agonist; 0, 10, 100, 1000 ng; n = 63), SCH23390 (D1-like antagonist; 0, 2500 ng; n = 27), quinpirole (D2-like agonist; 0, 10, 100, 1000 ng; n = 58), or sulpiride (D2-like antagonist; 0, 2500 ng; n = 24) once a day for four weeks. One noninjected group (n = 19) served as untreated control. Refractive states and axial dimensions of the eyes were measured without cycloplegia or general anesthetic, using eccentric infrared photoretinoscopy and A-scan ultrasonography, respectively, before treatment, and after 2 and 4 weeks of treatment. The main drug effects were analyzed by paired t-test or 2-way repeated measures ANOVA, as required. The naturally occurring progression of myopic RE was inhibited by apomorphine at relatively high doses (250 and 750 ng), SKF38393 at 100 ng (D1-like agonist), and sulpiride at 2500 ng (D2-like antagonist), but promoted by apomorphine at a lower dose (25 ng), quinpirole at 100 ng (D2-like agonist), and SCH23390 at 2500 ng (D1-like antagonist). All drugs affected primarily vitreous chamber depth, rather than anterior segment dimensions. Our data suggest that the activation of D1-like receptors inhibits, whereas activation of D2-like receptors promotes, progressive myopia in this animal model. The robust effects of antagonists suggest that ocular dopamine receptors in these albinos may be in a chronic state of partial excitation. The precise location and identity of the receptors responsible for these effects remain to be determined.

Impact of Ex Vivo Administration of Mesenchymal Stem Cells on the Function of Kidney Grafts From Cardiac Death Donors in Rat

BackgroundMesenchymal stem cells (MSCs) have been applied to the treatment of various diseases, and MSC administration in marginal donor grafts may help avoid the ischemia–reperfusion injury associated with solid organ transplants. Given the reports of side effects after intravenous MSC administration, local MSC administration to the target organ might be a better approach. We administered adipose tissue–derived MSCs (AT-MSCs) ex vivo to donor rat kidneys obtained after cardiac death (CD). MethodsUsing male Lewis rats (8–10 weeks), and a marginal transplant model of 1hr CD plus 1hr sub-normothermic ET-Kyoto solution preservation were conducted. AT-MSCs obtained from double-reporter (luciferase–LacZ) transgenic Lewis rats were injected either systemically (1.0 × 106 cells/0.5 mL) to bilaterally nephrectomized recipient rats that had received a marginal kidney graft (n = 6), or locally via the renal artery (500 μL ET-Kyoto solution containing the same number of AT-MSCs) to marginal kidney grafts, which were then preserved (1 hour; 22°C) before being transplanted into bilaterally nephrectomized recipient rats (n = 8). Serum was collected to assess the therapeutic effects of AT-MSC administration, and the recipients of rats surviving to Day 14 were separately evaluated histopathologically. Follow-up was by in vivo imaging and histological LacZ staining, and tumor formation was evaluated in MSC-injected rats at 3 months. ResultsSystemic injection of MSC did not improve recipient survival. In vivo imaging showed MSCs trapped in the lung that later became undetectable. Ex vivo injection of MSCs did show a benefit without adverse effects. At Day 14 after RTx, 75% of the rats in the AT-MSC–injected group (MSC[+]) had survived, whereas 50% of the rats in the AT-MSC–non-injected group (MSC[−]) had died. Renal function in the MSC(+) group was improved compared with that in the MSC(−) group at Day 4. LacZ staining revealed AT-MSCs attached to the renal tubules at 24 hours after RTx that later became undetectable. Histopathologic examination showed little difference in fibrosis between the groups at Day 14. No teratomas or other abnormalities were seen at 3 months.

Change of Retinal Nerve Fiber Layer Thickness in Various Retinal Diseases Treated With Multiple Intravitreal Antivascular Endothelial Growth Factor

To investigate the effect of multiple intravitreal injection of anti-VEGF on the retinal nerve fiber layer (RNFL) in AMD, diabetes mellitus retinopathy (DMR), and retinal vein occlusion (RVO). In this retrospective controlled case series, we reviewed the AMD, DMR, and RVO patients who received more than three anti-VEGF injections (injection group: 148 eyes). Patients without treatment were included as a control group (noninjection group: 183 eyes). RNFL thickness was measured by SD-OCT. Also, correlation between RNFL change and associated factors, including intraocular pressure (IOP), injection times, and severity of retinal ischemia, were analyzed using multivariate logistic regression. RNFL thickness (μm) had not changed in AMD, but it decreased from 100.0 to 97.1, and from 101.1 to 98.0 in injection groups of DMR and RVO, respectively, as well as the noninjection group. However, decreased RNFL thickness of the injection groups was not significantly different from those of the noninjection groups. Severity of retinal ischemia was associated with decreased RNFL thickness (odds ratio: 4.667). However, number of injections and IOP-related variables had no association with RNFL change. Multiple intravitreal injections of anti-VEGF did not lead to significant change in RNFL thickness in wet AMD, DMR, and RVO patients. Furthermore, IOP fluctuations and number of injections did not appear to adversely affect RNFL thickness. Decreased RNFL thickness associated with severity of retinal ischemia in the DMR and RVO patients suggests that inner retinal ischemia itself could be a cause of RNFL loss rather than anti-VEGF effect.

Comparison of Apolipoprotein E Knockout Mice and Spontaneously Hyperlipidemic Mice in Porphyromonas gingivalis-Induced Atherosclerosis

Porphyromonas gingivalis was shown to accelerate atheroma formation in murine models such as apolipoprotein E knockout (ApoE-KO) mice and BALB/c. apoE-deficient spontaneously hyperlipidemic (C. KOR-Apoeshl) mice. The purpose of this study is to characterize mouse gender and strain differences in P. gingivalis-induced atherosclerosis. Male and female ApoE-KO mice (10 weeks old) and age- and sex-matched C. KOR-Apoeshl mice were intravenously injected with P. gingivalis three times a week for 3 weeks. Mice were then killed at 14 weeks. Atherosclerotic plaques in the proximal aorta were determined by Oil Red O staining. Serum lipid parameters (total cholesterol, TC; high density lipoprotein, HDL; and low density lipoprotein, LDL) and body weights were evaluated. P. gingivalis injection significantly enhanced the formation of atherosclerotic plaque in both ApoE-KO and Apoeshl mice. Moreover, atherosclerotic lesion area was slightly larger in ApoE-KO mice than in Apoeshl mice, while both model mice displayed similar body weight gain regardless of bacterial infection. The weight gain of male was larger than that of female in the period, and the TC of Apoeshl mice was higher than that of ApoE-KO mice. Furthermore, P. gingivalis injection had elevated serum TC and LDL levels compared to the non-injected Apoeshl mice group. These results suggest that P. gingivalis induces atherosclerosis in both ApoE-KO and Apoeshl mice subsequently increasingTC and LDL levels. Thus, the Apoeshl mice may serve as a substitute for ApoEKO mice at the point of it being more natural and superior in examination of temporal change of morbidity, if we take account the import cost and the complication of maintenance of genetically modified mice.

Effects of the commercial in ovo injection of 25-hydroxycholecalciferol on broiler posthatch performance and carcass characteristics ,

In ovo injection of 25-hydroxycholecalciferol [25(OH)D3] has been shown to improve hatchability of injected broiler eggs. Effects of the in ovo injection of commercial diluent containing various levels of 25(OH)D3 on broiler posthatch performance and carcass characteristics were investigated in 2 trials. On each of 10 tray levels of a single-stage incubator, all treatment groups were randomly represented with each containing 21 and 40 eggs in trials 1 and 2, respectively. Treatments included noninjected and diluent-injected (100 µL commercial diluent-injected) controls, and those that received 0.15, 0.30, 0.60, or 1.20 µg of 25(OH)D3 in trial 1 and 0.20, 0.60, 1.80, or 5.4 µg of 25(OH)D3 in trial 2, in 100 µL of commercial diluent using a commercial multi-egg injector on d 18 of incubation. On d 21 of incubation, chicks from each treatment replicate group were placed in corresponding floor pens. Feed intake, BW gain, and feed conversion were determined for the weekly and cumulative 0 to 21 d age intervals in trial 1 and for the weekly and cumulative 0 to 48 d age intervals in trial 2. In trial 2, 2 birds from each sex were selected from each treatment replicate group for determination of processing carcass characteristics on d 49 posthatch. Feed intake in the 0 to 7, 7 to 14, and 14 to 21 d age intervals and BW gain in the 0 to 7 and 14 to 21 d age intervals were affected by treatment in trial 2. The in ovo injection of up to 1.20 and 0.60 µg of 25(OH)D3 in trials 1 and 2, respectively, did not affect the BW gain of birds during the 0 to 7, 7 to 14, and 14 to 21 d age intervals compared with the noninjected and diluent-injected control groups. It was concluded that the in ovo injection of up to 1.20 µg of 25(OH)D3 into the amnion has no detrimental effect on the overall posthatch performance of broilers.