Measuring the Level of Agreement for Lactate Measurements in Hispaniolan Amazon Parrots (Amazona ventralis) Among 2 Point-of-Care Analyzers and a Benchtop Analyzer.

Lactate is an important biochemistry analyte used in human and veterinary medicine to assess tissue perfusion and can be used as a prognostic indicator for certain disease conditions. Whereas lactate is commonly measured using "patient-side" handheld meters, these meters have not been validated for companion avian species. The purpose of this study was to measure the level of agreement between 2 commercially available point-of-care lactate meters and a laboratory benchtop blood analyzer in Hispaniolan Amazon parrots (Amazona ventralis). Blood samples were collected from 20 adult parrots at Louisiana State University by drawing 1.5 mL of blood from the right jugular vein. One drop of whole blood was used for the Lactate Plus analyzer and the remainder of the sample transferred into a lithium heparin microtainer. From the blood in the microtainer, 0.2 mL whole blood was analyzed using the epoc Blood Analysis System, and the remaining sample was centrifuged to obtain plasma that was immediately frozen at -80°C (-112°F) and submitted to the Texas A&M University Clinical Pathology Laboratory for analysis on the VITROS 4500 benchtop analyzer. Bland-Altman agreement plots and Passing-Bablok regression were used to measure the level of agreement between the methods. There was poor agreement between all 3 methods with mean percentage differences in lactate concentrations ≥22% (epoc and Lactate Plus: 33.6% [95% CI: 27-40]; epoc and VITROS 4500: 55% [95% CI:52-58]; VITROS 4500 and Lactate Plus: 22% [95% CI:16-28]). Based on these results, the point-of-care meters tested in this study are not interchangeable, and separate reference intervals were calculated for each method. Blood lactate concentrations may have more utility in tracing lactate trends over time in an individual rather than being able to utilize this information at 1 time point for disease diagnosis and prognosis.

Reptile Dermatology.

Reptiles are being presented more frequently to veterinarians because they increase in popularity. As with domestic pets, dermatologic conditions are common findings in captive reptiles and can be associated with husbandry and nutritional deficiencies, infectious diseases, and neoplasia. To have success with these cases, it is important to take a stepwise and strategic approach, starting with a thorough anamnesis and physical examination. From there, diagnostic tests should be pursued, with an understanding of the limitations of each diagnostic test. By understanding these limitations, the veterinary scientist can determine the best path to a diagnosis and treatment for the case.

Comparison of Two Stifle Exploratory Methods Using Mini-Arthrotomy for Diagnosis of Canine Medial Meniscal Pathology: An Ex Vivo Study.

OBJECTIVE: The main aim of this study was to compare the accuracy of stifle exploratory using either a stifle distractor (SD method) or a combination of Hohmann and Senn retractors (HS method) for diagnosing canine medial meniscal tears in cranial cruciate ligament-deficient stifles. STUDY DESIGN: Fifteen pairs of canine cadaveric pelvic limbs were used and cranial cruciate ligament were transected in all stifles. Paired limbs were then randomly assigned to one of five groups based on the tears created in the caudal pole of the medial meniscus: no tear, peripheral detachment, or a variation in three vertical longitudinal tears. A craniomedial mini-arthrotomy was performed by two observers and diagnosis of the medial meniscal status was made utilizing the HS and SD methods. Correct diagnosis of the meniscal tear was compared for both methods and observers. RESULTS: Correct diagnoses were made using the HS and SD methods in 24/30 and 24/30 cases for observer 1 respectively; and in 17/30 and 19/30 cases for observer 2 respectively. There was no significant difference in the correct diagnosis of meniscal tears within each observer between the two methods. CONCLUSION: Both HS and SD methods have equal accuracy for the diagnosis of canine medial meniscal pathology for a board-certified surgeon. Unassisted surgeons using the SD method for the evaluation of the medial meniscus are at no diagnostic disadvantage compared with assisted surgeons utilizing the HS method.

Canine memory T-cell subsets in health and disease.

A more complete understanding of canine T-lymphocyte immunity is necessary for improving diagnostic and therapeutic approaches to canine diseases, developing cell-based canine immunotherapeutics, and evaluating dogs as large mammal models for comparative immunology research. The aim of this study was to utilize CD45RA (indicating antigen inexperience) and CD62L (indicating lymph node homing capability), to quantify canine memory T-cell subsets in healthy dogs and dogs with various diseases. Peripheral blood mononuclear cells (PBMCs) were prospectively collected from dogs belonging to one of four groups:dermatologic inflammation (n = 9), solid tumors (n = 9), lymphoma (n = 9), and age-/weight-matched healthy control dogs (n = 15). Dogs receiving prednisone or any other immunomodulating medication within two weeks were excluded. Flow cytometry was performed and T-cell subsets were defined as CD4+ or CD8+, and naïve (TN), central memory (CM), effector memory (EM), or terminal effector memory re-expressing CD45RA (TEMRA). T-cell subset proportions were compared between each disease group and their healthy age-/weight-matched controls using a Mann-Whitney test. Significantly increased %CD8+ TN (P = 0.036) and decreased %CD8+ TEMRA (P = 0.045) were detected in dogs with dermatologic inflammation compared to healthy controls. Furthermore, %CD4+ TN positively correlated with Canine Atopic Dermatitis Extent and Severity Index (CADESI) score within the inflammation group (ρ = 0.817, P = 0.011). No significant differences between either cancer group and their healthy controls were detected. Taken together, these data indicate that dermatologic inflammation can alter proportions of peripheral blood T-cell subsets, possibly due to the migration of antigen-specific T-cells into tissues. Furthermore, these findings support the utility of CD45RA and CD62L in characterizing clinical canine immune responses.

Effects of Isoflurane Anesthesia on the Hematologic Values of Rehabilitated Wild Owls.

Isoflurane anesthesia is commonly used for owls when they are being rehabilitated to minimize stress during treatments and procedures, as well as to ensure caretaker safety. However, the effects of isoflurane anesthesia on the hematologic response of owls are not known. To investigate the effects of isoflurane anesthesia on the hematology of owls, 3 phases of investigation were performed on the subject animals: 1) single, short manual- versus single, short isoflurane-restraint episodes (n = 12; 38%); 2) a single, prolonged isoflurane episode (n = 10; 31%); and 3) serial, short isoflurane episodes (n = 10; 31%). All owls were classified as adult, and the sex for most individuals was unknown. Twelve owls (38%) were included in phase 1: 5 great horned owls (Bubo virginianus; 42%), 2 eastern screech owls (Megascops asio; 17%), and 5 barred owls (Strix varia; 42%). A separate cohort of 10 novel owls (31%) were selected for inclusion in both phases 2 and 3: 4 great horned owls (40%), 2 eastern screech owls (20%), 2 barred owls (20%), 1 barn owl (Tyto alba; 10%), and 1 snowy owl (Bubo scandiacus; 10%). For each anesthetic episode, blood was collected within 3 minutes of capture and in 15-minute intervals according to the duration of the procedure. Phase 2 had additional blood collections with the patient awake at 2 and 24 hours after time 0 blood collection, whereas phase 3 had an additional blood collection at 24 hours after time 0 blood collection. Hematologic analyses included packed cell volume, total solids, total white blood cell count, heterophil to lymphocyte ratio, and absolute heterophil, lymphocyte, monocyte, eosinophil, and basophil counts. Total white blood cell count decreased significantly during phase 1; packed cell volume decreased significantly during phases 2 and 3; total solids decreased significantly in phase 2; phase 2 demonstrated a lymphopenia with a concurrent decrease in the heterophil to lymphocyte ratio; and phase 3 demonstrated a heteropenia and significant changes in the eosinophil count. All hematologic changes noted in the study were within appropriate reference intervals for the owls but do suggest that there are physiologic consequences of restraining and anesthetizing these avian patients.

Macrorhabdus ornithogaster Infection and Spontaneous Proventricular Adenocarcinoma in Budgerigars ( Melopsittacus undulatus).

Proventricular infection with the anamorphic, ascomycetous yeast Macrorhabdus ornithogaster and disease associated with infection (macrorhabdiosis) have been widely reported in budgerigars ( Melopsittacus undulatus). Proventricular adenocarcinoma has also been previously reported in this species. In a retrospective archival search of clinical cases submitted to a zoo animal and exotic pet pathology service between 1998 and 2013, a total of 28 128 avian submissions were identified, which included 1006 budgerigars kept in zoos or aviaries or as pets. Of these budgerigars, 177 were identified histologically as infected with M. orthithogaster at the time of necropsy. Histologic examination of tissues from budgerigars infected with M. orthithogaster identified an apparent continuum in the development of proventricular isthmus lesions associated with M. ornithogaster that included inflammation, mucosal hyperplasia, glandular dysplasia, and adenocarcinoma. Proventricular adenocarcinoma was identified histologically in 21 budgerigars. Budgerigars with proventricular adenocarcinoma were significantly more likely to have macrorhabdiosis than budgerigars without proventricular adenocarcinoma. Based on odds ratios for archival data, budgerigars were 41 times (95% confidence interval [CI], 33-52) more likely to have macrorhabdiosis than other avian species and 19 times (95% CI, 11-33) more likely to have proventricular adenocarcinoma than other birds. Budgerigars were 323 times (95% CI, 42-2490) more likely to be affected by both diseases simultaneously compared with other avian species. These findings suggest that macrorhabdiosis may be an associated factor for proventricular adenocarcinoma, although the explanation for this statistically significant correlation remains unknown and further investigation is warranted.

Effect of refrigeration of clinical canine urine samples on quantitative bacterial culture.

OBJECTIVE To examine the effect of 24 hours of refrigeration on urine samples collected from dogs with signs of urinary tract infection (UTI). DESIGN Prospective cross-sectional study. ANIMALS 104 dogs with signs consistent with UTI that had a urine sample collected via cystocentesis as part of their diagnostic workup. PROCEDURES A 1-mL aliquot of each urine sample was refrigerated at 5°C for 24 hours in a plain glass tube, then processed for quantitative bacterial culture (QBC). A 0.5-mL aliquot was added to 3 mL of tryptic soy broth (TSB) and refrigerated at 5°C for 24 hours, then processed for QBC. The remaining portion was immediately processed for QBC, with results reported as numbers of bacterial colony-forming units (CFUs). Sensitivity of the QBC for detection of bacteria (and therefore UTI) was determined for sample refrigeration in the 2 conditions, compared with immediate processing (reference standard). RESULTS Bacterial growth was identified in 35.6% (n = 37), 33.7% (35), and 31.7% (33) of the immediately processed, refrigerated, and refrigerated-in-TSB urine samples, respectively. Sample refrigeration without TSB resulted in no significant difference in CFU counts relative to immediate processing; however, the sensitivity of this method was 95% (35/37). Sample refrigeration with TSB resulted in significantly lower CFU counts, and sensitivity was only 89% (33/37). CONCLUSIONS AND CLINICAL RELEVANCE Canine urine samples collected for bacterial culture should be immediately submitted for testing. Although CFU counts for refrigerated and immediately processed samples were statistically similar in this study, sample refrigeration in enrichment broth resulted in imperfect sensitivity for UTI detection and is not recommended.

Characterization of long-term elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate beads in vitro by two distinct sample collection methods.

OBJECTIVE To characterize long-term elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CI-CSH) beads in vitro by comparing 2 distinct sample collection methods designed to mimic 2 in vivo environments. SAMPLES 162 CI-CSH beads containing 4.6 mg of carboplatin (2.4 mg of platinum/bead). PROCEDURES For method 1, which mimicked an in vivo environment with rapid and complete fluid exchange, each of 3 plastic 10-mL conical tubes contained 3 CI-CSH beads and 5 mL of PBS solution. Eluent samples were obtained by evacuation of all fluid at 1, 2, 3, 6, 9, and 12 hours and 1, 2, 3, 6, 9, 12, 15, 18, 22, 26, and 30 days. Five milliliters of fresh PBS solution was then added to each tube. For method 2, which mimicked an in vivo environment with no fluid exchange, each of 51 tubes (ie, 3 tubes/17 sample collection times) contained 3 CI-CSH beads and 5 mL of PBS solution. Eluent samples were obtained from the assigned tubes for each time point. All samples were analyzed for platinum content by inductively coupled plasma-mass spectrometry. RESULTS Platinum was released from CI-CSH beads for 22 to 30 days. Significant differences were found in platinum concentration and percentage of platinum eluted from CI-CSH beads over time for each method. Platinum concentrations and elution percentages in method 2 samples were significantly higher than those of method 1 samples, except for the first hour measurements. CONCLUSIONS AND CLINICAL RELEVANCE Sample collection methods 1 and 2 may provide estimates of the minimum and maximum platinum release, respectively, from CI-CSH beads in vivo.

Reproductive Medicine in Freshwater Turtles and Land Tortoises.

Chelonian reproductive medicine is an extremely important facet to ensuring captive populations for the pet trade and conservation efforts around the globe. This article covers basic chelonian reproductive anatomy and physiology, natural history, behavior, and sexing chelonians, in addition to discussing reproductive disorders that are commonly seen by veterinarians. Reproductive disorders covered include infertility, dystocia, follicular stasis, egg yolk coelomitis, phallus prolapse, and reproductive neoplasia. It is hoped that this information will allow clinicians to recognize, understand, and successfully treat reproductive disorders in chelonians, thus providing the best available care for our chelonian patients.

Elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate beads in vitro.

OBJECTIVE To characterize the elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CSH) beads in vitro. SAMPLE 60 carboplatin-impregnated CSH beads and 9 CSH beads without added carboplatin (controls). PROCEDURES Carboplatin-impregnated CSH beads (each containing 4.6 mg of carboplatin [2.4 mg of platinum]) were placed into separate 10-mL plastic tubes containing 5 mL of PBSS in groups of 1, 3, 6, or 10; 3 control beads were placed into a single tube of PBSS at the same volume. Experiments were conducted in triplicate at 37°C and a pH of 7.4 with constant agitation. Eluent samples were collected at 1, 2, 3, 6, 12, 24, and 72 hours. Samples were analyzed for platinum content by inductively coupled plasma-mass spectrometry. RESULTS The mean concentration of platinum released per carboplatin-impregnated bead over 72 hours was 445.3 mg/L. Cumulative concentrations of platinum eluted increased as the number of beads per tube increased. There was a significant difference in platinum concentrations over time, with values increasing over the first 12 hours and then declining for all tubes. There was also a significant difference in percentage of total incorporated platinum released into tubes with different numbers of beads: the percentage of eluted platinum was higher in tubes containing 1 or 3 beads than in those containing 6 or 10 beads. CONCLUSIONS AND CLINICAL RELEVANCE Carboplatin-impregnated CSH beads eluted platinum over 72 hours. Further studies are needed to determine whether implantation of carboplatin-impregnated CSH beads results in detectable levels of platinum systemically and whether the platinum concentrations eluted locally are toxic to tumor cells.

Evaluating the clinical and physiological effects of long term ultraviolet B radiation on guinea pigs (Cavia porcellus).

Vitamin D is an important hormone in vertebrates. Most animals acquire this hormone through their diet, secondary to exposure to ultraviolet B (UVB) radiation, or a combination thereof. The objectives for this research were to evaluate the clinical and physiologic effects of artificial UVB light supplementation on guinea pigs (Cavia porcellus) and to evaluate the long-term safety of artificial UVB light supplementation over the course of six months. Twelve juvenile acromelanic Hartley guinea pigs were randomly assigned to one of two treatment groups: Group A was exposed to 12 hours of artificial UVB radiation daily and Group B received only ambient fluorescent light for 12 hours daily. Animals in both groups were offered the same diet and housed under the same conditions. Blood samples were collected every three weeks to measure blood chemistry values, parathyroid hormone, ionized calcium, and serum 25-hydroxyvitamin D3 (25-OHD3) levels. Serial ophthalmologic examinations, computed tomography scans, and dual energy x-ray absorptiometry scans were performed during the course of the study. At the end of the study the animals were euthanized and necropsied. Mean ± SD serum 25-OHD3 concentrations differed significantly in the guinea pigs (p<0.0001) between the UVB supplementation group (101.49±21.81 nmol/L) and the control group (36.33±24.42 nmol/L). An increased corneal thickness in both eyes was also found in the UVB supplementation compared to the control group (right eye [OD]: p<0.0001; left eye [OS]: p<0.0001). There were no apparent negative clinical or pathologic side effects noted between the groups. This study found that exposing guinea pigs to UVB radiation long term significantly increased their circulating serum 25-OHD3 levels, and that this increase was sustainable over time. Providing guinea pigs exposure to UVB may be an important husbandry consideration that is not currently recommended.

Effects of sevoflurane anesthesia on righting reflex and hemolymph gas analysis variables for Chilean rose tarantulas (Grammostola rosea).

OBJECTIVE: To determine the safety, efficacy, and effects on hemolymph gas analysis variables of sevoflurane anesthesia in Chilean rose tarantulas (Grammostola rosea). ANIMALS: 12 subadult Chilean rose tarantulas of unknown sex. PROCEDURES: Spiders were anesthetized in a custom chamber with sevoflurane (5% in oxygen [1.0 L/min]), then allowed to recover in 100% oxygen. Righting reflex was evaluated every 3 minutes during anesthesia to determine time to anesthetic induction and recovery. Hemolymph samples were collected from an intracardiac location prior to and after induction of anesthesia and evaluated to determine various gas analysis variables. RESULTS: Mean ± SD induction and recovery times were 16 ± 5.91 minutes and 29 ± 21.34 minutes, respectively. Significant differences were detected for Po2, base excess, and glucose and ionized magnesium concentrations between hemolymph samples obtained before anesthesia and those obtained after induction of anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE-Results of this study suggested that the use of sevoflurane as an anesthetic agent for Chilean rose tarantulas was safe and effective. Various hemolymph sample gas analysis values changed during anesthesia.

Effects of ultraviolet radiation produced from artificial lights on serum 25-hydroxyvitamin D concentration in captive domestic rabbits (Oryctolagus cuniculi).

OBJECTIVE: To determine the effects of UVB radiation produced by artificial lights on serum 25-hydroxyvitamin D concentrations in domestic rabbits (Oryctolagus cuniculi). ANIMALS: 9 juvenile domestic rabbits. PROCEDURES: After an acclimation period, rabbits were anesthetized with isoflurane, and an initial blood sample was collected for determination of serum 25-hydroxyvitamin D concentration. Rabbits were randomly assigned to receive 12-hour exposure to UVB radiation produced by 2 compact fluorescent lights daily (n = 5) or no UVB supplementation (4) commencing on day 1. The UVB radiation emitted into the cage was measured at 9 points approximately 34 cm from the surface of the UVB light sources (representing the position of the rabbits in the cage) after 10 hours of exposure on days 1, 8, and 14. On day 14, another blood sample was collected from anesthetized rabbits for determination of serum 25-hydroxyvitamin D concentration. RESULTS: The UVB radiation level was 8.3 to 58.1 µW/cm² for the exposed rabbits and consistently < 0.001 µW/cm² for the control rabbits. Mean ± SD serum 25-hydroxyvitamin D concentrations in the rabbits that were or were not provided supplemental UVB radiation for 14 days differed significantly (66.4 ± 14.3 nmol/L and 31.7 ± 9.9 nmol/L, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Exposure to UVB radiation produced by artificial light significantly increased serum 25-hydroxyvitamin D concentration in juvenile rabbits. Because vitamin D is an essential hormone in vertebrates, these findings suggested that the provision of supplemental UVB radiation to captive rabbits may be important.

Use of lidocaine-bupivacaine-infused absorbable gelatin hemostatic sponges versus lidocaine-bupivacaine retrobulbar injections for postoperative analgesia following eye enucleation in dogs.

OBJECTIVE: To compare use of lidocaine-bupivacaine-infused absorbable gelatin hemostatic sponges versus lidocaine-bupivacaine retrobulbar injections for postoperative analgesia in dogs following eye enucleation. DESIGN: Randomized case-control study. ANIMALS: 19 dogs that underwent eye enucleation. PROCEDURES: 19 client-owned dogs admitted to a referral hospital for routine eye enucleation were enrolled with owner consent and randomly assigned to receive an orbital absorbable gelatin hemostatic sponge infused with lidocaine and bupivacaine after globe removal (n = 8) or retrobulbar injection of lidocaine and bupivacaine before globe removal (11). Baseline pain scores were recorded on the basis of an ordinal pain scale. Anesthetic premedication consisted of hydromorphone, midazolam, and glycopyrrolate. Propofol was used for anesthetic induction and isoflurane for maintenance. A transpalpebral eye enucleation was performed by a board-certified ophthalmologist. Pain scores and heart rate were again recorded 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours after extubation by trained observers masked to treatment groups. Dogs were given hydromorphone as rescue analgesia if the total pain score was ≥ 9 of 18 or any categorical pain score was ≥ 3 (on a scale from 0 to 3 or 0 to 4). RESULTS: There were significant differences over time for comfort level, response to touch, behavior, heart rate, and total pain score; however, there was no difference between treatment groups. One dog in the absorbable gelatin hemostatic sponge group required rescue hydromorphone 4 hours after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: The absorbable gelatin hemostatic sponge proved to be as effective in providing local analgesia for eye enucleation in dogs as the retrobulbar injections.

Measuring the Level of Agreement Between Cloacal Gram's Stains and Bacterial Cultures in Hispaniolan Amazon Parrots ( Amazona ventralis ).

Cloacal or fecal Gram's stains and bacterial cultures are routinely performed during avian physical examinations to assess the microbial flora of the gastrointestinal tract. Although cloacal or fecal Gram's stains and bacterial cultures are considered routine diagnostic procedures, the level of agreement between the individual tests has not been determined. To investigate the level of agreement between results from Gram's stain and bacterial culture when used to assess cloacal or fecal samples from psittacine birds, samples were taken from 21 clinically healthy Hispaniolan Amazon parrots ( Amazona ventralis ) and tested by Gram's stain cytology and bacterial culture. Most bacteria (97.2%) identified by Gram's stain were gram positive. However, gram-negative organisms were identified in 7 of 21 (33.3%; 95% confidence interval: 13.3%-53.3%) birds. Escherichia coli was the only gram-negative organism identified on culture. Agreement between results of Gram's stain and culture was fair (weighted κ = 0.27). The results of this study suggest that Gram's stains and bacterial culture may need to be performed with a parallel testing strategy to limit the likelihood of misclassifying the microbial flora of psittacine patients.

Advancement flap as a novel treatment for a pododermatitis lesion in a red-tailed hawk (Buteo jamaicensis).

Pododermatitis is a pathologic condition commonly reported in captive raptors and characterized by swelling, excoriation, ulceration, cellulitis, or abscessation of the plantar aspect of the foot. Its cause can be multifactorial, often involving abnormal weight bearing or poor sanitation, and medical and surgical techniques, in addition to environmental alterations, are hallmarks of treatment. In this case, a single pedicle advancement flap was used to treat chronic, nonresponsive grade V/VII pododermatitis of the right metatarsal pad in a red-tailed hawk (Buteo jamaicensis). The advancement flap was formed by using the interdigital skin between digits 3 and 4. The double layer of skin was incised and separated, and the leading edge of the flap was then advanced over the defect and secured with simple interrupted subcutaneous and skin sutures. The foot was bandaged after surgery to take pressure off the surgical site. At 58 days after the surgery, the hawk was deemed medically sound with no signs of pododermatitis and was released to a wildlife rehabilitator. The use of a single pedicle advancement flap has not previously been reported for the treatment of pododermatitis.

Relationship between potential aggregation-prone regions and HLA-DR-binding T-cell immune epitopes: implications for rational design of novel and follow-on therapeutic antibodies.

Aggregation and unwanted immunogenicity are hurdles to avoid in successful commercial development of antibody-based therapeutics. In this article, the relationship between aggregation-prone regions (APRs), capable of forming cross-ß motifs/amyloid fibrils, and major histocompatibility complex class II-restricted human leukocyte antigen (HLA)-DR-binding T-cell immune epitopes (TcIEs) is analyzed using amino acid sequences of 25 therapeutic antibodies, 55 TcIEs recognized by T-regulatory cells (tregitopes), 1000 randomly generated 15-residue-long peptides, 2257 human self-TcIEs (autoantigens), and 11 peptides in HLA-peptide cocrystal structures. Sequence analyses from these diverse sources consistently show a high level of correlation between APRs and TcIEs: approximately one-third of TcIEs contain APRs, but the majority of APRs occur within TcIE regions (TcIERs). Tregitopes also contain APRs. Most APR-containing TcIERs can bind multiple HLA-DR alleles, suggesting that aggregation-driven adverse immune responses could impact a broad segment of patient population. This article has identified common molecular sequence-structure loci that potentially contribute toward both manufacturability and safety profiles of the therapeutic antibodies, thereby laying a foundation for simultaneous optimization of these attributes in novel and follow-on candidates. Incidence of APRs within TcIERs is not special to biotherapeutics, self-TcIEs from human proteins, involved in various diseases, also contain predicted APRs and experimentally proven amyloid-fibril-forming peptide sequence portions.

Evaluation of the histologic reactions to commonly used suture materials in the skin and musculature of ball pythons (Python regius).

OBJECTIVE: To evaluate histologic reactions to 8 suture materials and cyanoacrylate tissue adhesive (CTA) in the musculature and skin of ball pythons. ANIMALS: 30 hatchling ball pythons. PROCEDURES: In each snake, ten 1-cm skin incisions were made (day 0). At 8 sites, a suture of 1 of 8 materials was placed in the epaxial musculature, and the incision was closed with the same material. One incision was closed by use of CTA. No suture material was placed in the tenth incision, which was allowed to heal by second intention (negative control). Snakes (n = 5/group) were euthanized for harvest of treatment-site tissues at days 3, 7, 14, 30, 60, and 90. Skin and muscle sections were examined microscopically and assigned a subjective score (0 to 4) for each of the following: overall severity of inflammation, fibrosis, number of macrophages, number of granulocytes, number of perivascular lymphocytes, and degree of suture fragmentation. RESULTS: Subjective score analysis revealed that CTA did not cause a significant inflammatory response, compared with the negative control. All suture materials caused significantly more inflammation over all time points; for all suture materials, inflammatory response scores were significantly higher than values for the negative control 90 days after implantation. No sutures were completely absorbed by the end of the study period, and several sutures appeared to be in the process of extrusion. CONCLUSIONS AND CLINICAL RELEVANCE: In snakes, CTA can be used to close small superficial incisions or lacerations with minimal inflammatory response, and sutures may undergo extrusion from tissues prior to complete absorption.