IL-31RA and TRPV1 Expression in Atopic Dermatitis Induced with Trinitrochlorobenzene in Nc/Nga Mice.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Interleukin 31 (IL-31), a novel cytokine in AD, causes pruritus, typically characteristic of AD patients. The transient receptor potential vanilloid type 1 (TRPV1) is a cation channel activated by diverse noxious stimuli that has been studied in a variety of pruritic skin diseases. In this study, the AD animal model was generated by administering the hapten, trinitrochlorobenzene (TNCB), to Nc/Nga mice, and the degree of expression of the IL-31 receptor alpha (IL-31RA) and TRPV1 in the skin of these atopic models was evaluated. The Nc/Nga mice were divided into 3 groups: control, TNCB 2-weeks treated, and TNCB 8-weeks treated. After inducing AD, the skin lesions in each group were scored and compared, and the histology of the skin lesions and the IL-31RA and TRPV1 expression for each group were evaluated by analyzing immunohistochemistry. The results show a significant difference in the skin lesion scores between the groups. The immunohistochemistry evaluation highlighted the remarkable expression of IL-31RA and TRPV1 in the nerve fibers of the TNCB 8-weeks-treated group. We thus confirmed that the long-term application of TNCB induced chronic atopic-like dermatitis and that IL-31RA and TRPV1 were overexpressed in the peripheral nerve fibers in this AD model.

Neuropathological changes in dorsal root ganglia induced by pyridoxine in dogs.

BACKGROUND: Pyridoxine (PDX; vitamin B6), is an essential vitamin. PDX deficiency induces various symptoms, and when PDX is misused it acts as a neurotoxicant, inducing severe sensory neuropathy. RESULTS: To assess the possibility of creating a reversible sensory neuropathy model using dogs, 150 mg/kg of PDX was injected subcutaneously into dogs for 7 days and body weight measurements, postural reaction assessments, and electrophysiological recordings were obtained. In addition, the morphology of dorsal root ganglia (DRG) and changes in glial fibrillary acidic protein (GFAP) immunoreactive satellite glial cells and ionized calcium-binding adapter molecule 1 (Iba-1) immunoreactive microglia/macrophages were assessed at 1 day, 1 week, and 4 weeks after the last PDX treatment. During the administration period, body weight and proprioceptive losses occurred. One day after the last PDX treatment, electrophysiological recordings showed the absence of the H-reflex in the treated dogs. These phenomena persisted over the four post-treatment weeks, with the exception of body weight which recovered to the pre-treatment level. Staining (CV and HE) results revealed significant losses of large-sized neurons in the DRG at 1 day and 1 week after PDX treatment cessation, but the losses were recovered at 4 weeks post-treatment. The Iba-1 and GFAP immunohistochemistry results showed pronounced increases in reactive microglia/macrophage and satellite glial cell at 1 day and 1 week, respectively, after the last PDX treatment, and thereafter, immunoreactivity decreased with increasing time after PDX treatment. CONCLUSIONS: The results suggest that PDX-induced neuropathy is reversible in dogs; thus, dogs can be considered a good experimental model for research on neuropathy.

Two-weeks repeated-dose oral toxicity study of Pediococcus acidilactici J9 in a mice model.

BACKGROUND: Helicobacter pylori (H. pylori) is an important pathogen that causes chronic gastritis and peptic ulcer, and is related to the development of gastric carcinoma. Several chemicals, including antibiotics, have been used to eradicate H.pylori. However, more studies are yet requred to accomplish a sufficient therapy. Pediococcus acidilactici (P. acidilactici) J9 were studied for inhibition of binding of H.pylori binding to human gastric cell lines. This study was performed in order to investigate the repeated-dose toxicity of P. acidilactici J9 in male and female mice. RESULTS: C57BL/6 male and female Mus musculus were divided into four groups (n = 10 in each group). P. acidilactici J9 was administered daily by oral injection of vehicle control at dosage levels to a low-dose group (500 mg/kg/day), middle-dose group (1000 mg/kg/day), and high-dose group (2000 mg/kg/day) for 2 weeks. After 14 days of exposure, the blood biochemistry and hematology were investigated, along with a histopathology exam. There were no bacterial-related deaths or abnormal clinical signs in either gender of mouse. The data was observed during the period in terms of body weight, food intake, and water consumption. Also, no alterations in organ weights upon administration of P. acidilactici J9 alone were observed. The adhesion and growth of H. pylori were inhibited by a 24 h treatment of H. pylori and P. acidilactici J9 on adenocarcinoma gastric (AGS) cells, which are gastric cancer cells. Compared to the control group (AGS cell and H. pylori), the number of H. pylori analyzed by FACS significantly (p < 0.01) decreased after incubation of AGS cell with P. acidilactici J9 for 24 h. CONCLUSIONS: These results suggest that the oral application of P. acidilactici J9, up to a dosage level of 2000 mg/kg/day, causes no adverse effects in both male and female mice. P. acidilactici J9 inhibits the adhesion of H.pylori to AGS cancer cells. When used as probiotics, P. acidilactici J9 may help decrease the occurrence of gastritis and reduce the risk of H.pylori infection with promising safety issues.

Transient Fanconi Syndrome After Treatment with Firocoxib, Cefadroxil, Tramadol, and Famotidine in a Maltese.

Fanconi syndrome is a renal proximal tubulopathy characterized by excessive urinary loss of glucose, amino acids, several electrolytes, and bicarbonate. Here, we report the case of transient Fanconi syndrome in a dog following administration of firocoxib, cefadroxil, tramadol, and famotidine. A 10 mo old Maltese was presented with lethargy, anorexia, vomiting, and weight loss. Transient Fanconi syndrome without azotemia was associated with firocoxib, cefadroxil, tramadol, and famotidine treatment. The dog received supportive care including IV fluids, gastroprotectants, and oral nutritional supplements. Two months after initial diagnosis and treatment, the dog showed complete resolution of glucosuria and aminoaciduria. The unique features of Fanconi syndrome in this case emphasize the potential renal tubular toxicity of this widely used multiple-drug combination.

MicroRNA-27a reduces mutant hutingtin aggregation in an in vitro model of Huntington's disease.

Huntington's disease (HD) is a fatal genetic disease caused by abnormal aggregation of mutant huntingtin protein (mHtt). Reduction of mHtt aggregation decreases cell death of the brain and is a promising therapeutic strategy of HD. MicroRNAs are short non-coding nucleotides which modulate various genes and dysregulated in many diseases including HD. MicroRNA miR-27a was reported to be reduced in the brain of R6/2 HD mouse model and modulate multidrug resistance protein-1 (MDR-1). Using subventricular zone-derived neuronal stem cells (NSCs), we used in vitro HD model to test the effect of miR-27a on MDR-1 and mHtt aggregation. R6/2-derived NSCs can be differentiated under condition of growth factor deprivation, and the progression of differentiation leads to a decrease of MDR-1 level and efflux function of cells. Immunocytochemistry result also confirmed that mHtt aggregation was increased with differentiation. We transfected miR-27a in the R6/2-derived differentiated NSCs, and examined phenotype of HD, mHtt aggregation. As a result, miR-27a transfection resulted in reduction of mHtt aggregation in HD cells. In addition, MDR-1, which can transport mHtt, protein level was increased by miR-27a transfection. Conversely, knock-down of MDR-1 through MDR-1 siRNA increased mHtt aggregation in vitro. Our results indicate that miR-27a could reduce mHtt level of the HD cell by augmenting MDR-1 function.

SP, CGRP changes in pyridoxine induced neuropathic dogs with nerve growth factor gene therapy.

BACKGROUND: Nerve growth factor (NGF) is known not only as a major factor for neuronal plasticity but also as a pain stimulator. Although there have been several trials with NGF for its application in the regeneration or protection of the nervous system, the pain induced by NGF remains a challenge to be overcome. In this study, the pain induced by NGF gene therapy was evaluated. RESULTS: Vehicle or recombinant dog NGF plasmid was administered into the intrathecal space of dogs. Twenty-four hours after the vehicle or NGF plasmid inoculation, dogs were subcutaneously treated with 150 mg/kg pyridoxine every day for 7 days. For pain assessment, physical examination and electrophysiological recording were performed. Only in the vehicle-treated group, weight loss occurred, while NGF plasmid inoculation significantly improved this physical abnormalities. In the vehicle-treated group, electrophysiological recordings showed that H-reflex disappeared at 24 h after the last pyridoxine treatment. However, in the NGF plasmid inoculated group, the H-reflex were normal. In the results of immunohistochemistry, the NGF plasmid administration efficiently expressed in the dorsal root ganglia and significantly increased the pyridoxine-induced reduction of calcitonin gene-related peptide (CGRP) immunoreactive neurons, but not in substance P immunoreactive neurons, in the dorsal root ganglia. CONCLUSIONS: Given these results, we reason that NGF gene therapy in pyridoxine induced neuropathic dogs does not induce neuropathic pain with this dosage, even with increasing the expression of CGRP.

The protective effect of growth hormone on Cu/Zn superoxide dismutase-mutant motor neurons.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. The gene encoding Cu/Zn superoxide dismutase (SOD1) is responsible for 20% of familial ALS cases. Growth hormone (GH) concentrations are low in the cerebrospinal fluid of patients with ALS; however, its association with motoneuronal death is not known. We tested the neuroprotective effects of GH on human SOD-1-expressing cultured motor neurons and SOD1G93A transgenic mice. RESULTS: In cultured motor neurons, cytotoxicity was induced by A23187, GNSO, or homocysteine, and the effects of GH were determined by MTT, bax, PARP cleavage pattern, Hoechst nuclear staining, MAPK, and PI3K assay. In SOD-1 transgenic mice, rotarod motor performance was evaluated. Survival analysis of motoneuronal loss was done using cresyl violet, GFAP, and Bcl-2 staining. GH prevents motorneuronal death caused by GSNO and homocysteine, but not that by A23187. It activates MAPK and PI3K. GH-treated mice showed prolonged survival with improved motor performance and weight loss. GH decreased cresyl violet positive motoneuronal loss with strong Bcl-2 and less GFAP immunoreactivity. CONCLUSIONS: Our results demonstrate that GH has a protective effect on mutant SOD-1-expressing motor neurons.

Nuclear localization of huntingtin during spermatogenesis.

Huntingtin is a ubiquitous cytoplasmic protein. Mutant huntingtin causes Huntington's disease and its intranuclear inclusion is associated with cytotoxicity. Nuclear localization of normal huntingtin is detected in the oocyte up to 2.5 days post coitum. Therefore, huntingtin is expected to reside in the nucleus even before fertilization. The present study determined normal huntingtin distribution during spermatogenesis. Testicles from an adult male Sprague-Dawley rat were stained with anti-huntingtin antibody and nuclear counterstaining was performed with 4',6-diamidino-2-phenylindole. Concerning nuclear localization, huntingtin was detected in the spermatids, whereas predominant cytoplasmic localization of it was evident in the spermatogonia. Between the primary and secondary spermatocytes, huntingtin appeared to be delocalized in the nuclei when meiosis occurred. The findings provide evidence that normal huntingtin is transported to the nuclear compartment during the meiotic stage of spermatogenesis.

Computed tomographic evaluation of portal vein indices in cats with the extrahepatic portosystemic shunts.

IMPORTANCE: The portal vein to aorta (PV/Ao) ratio is used to assess the clinical significance of extrahepatic portosystemic shunt (EHPSS). Previous studies using computed tomography (CT) were conducted in dogs but not in cats. OBJECTIVE: This study aimed to establish normal reference values for PV indices (PV/Ao ratio and PV diameter) in cats and determine the usefulness of these for predicting symptomatic EHPSS. METHODS: This study included 95 dogs and 114 cats that underwent abdominal CT. The canine normal (CN) group included dogs without EHPSS. The cats were classified into feline normal (FN, 88/114), feline asymptomatic (FA, 16/114), and feline symptomatic (FS, 10/114) groups. The PV and Ao diameters were measured in axial cross-sections. RESULTS: The group FN had a higher PV/Ao ratio than the group CN (p < 0.001). Within the feline groups, the PV indices were in the order FN > FA > FS (both p < 0.001). The mean PV diameter and PV/Ao ratio for group FN were 5.23 ± 0.77 mm and 1.46 ± 0.19, respectively. The cutoff values between groups FN and FS were 4.115 mm for PV diameter (sensitivity, 100%; specificity, 97.7%) and 1.170 for PV/Ao ratio (90%, 92.1%). The cutoff values between group FA and FS were 3.835 mm (90%, 93.8%) and 1.010 (70%, 100%), respectively. CONCLUSIONS AND RELEVANCE: The results demonstrated significant differences in PV indices between dogs and cats. In cats, the PV/Ao ratio demonstrated high diagnostic performance for symptomatic EHPSS. The PV diameter also performed well, in contrast to dogs.

Analyzing small RNA sequences from canine stem cell-derived extracellular vesicles primed with TNF-α and IFN-γ and exploring their potential in lung repair.

Acute lung injury is an acute inflammation disorder that disrupts the lung endothelial and epithelial barriers. In this study, we investigated the extracellular vesicles (EVs) obtained via priming inflammatory cytokines such as tumor necrosis factor (TNF)-α and interferon (IFN)-γ on canine adipose mesenchymal stem cells in improving their anti-inflammatory and/or immunosuppressive potential, and/or their ability to alleviate lipopolysaccharide-induced lung injury in vitro. We also explored the correlation between epithelial-to-mesenchymal transition and the inflammatory repressive effect of primed EVs. Using small RNA-Seq, we confirmed that miR-16 and miR-502 significantly increased in EVs from TNF-α and IFN-γ-primed canine adipose mesenchymal stem cells. The pro and anti-inflammatory cytokines were analyzed in a lipopolysaccharide-induced lung injury model and we found that the EV anti-inflammatory effect improved on priming with inflammatory cytokines. EVs obtained from primed stem cells effectively suppress endothelial-to-mesenchymal transition in a lung injury model. Our results suggest a potential therapeutic approach utilizing EVs obtained from adipose mesenchymal stem cells primed with TNF-α and IFN-γ against lung inflammation and endothelial to mesenchymal transition.

Simultaneous hypersensitivity reactions to trimethoprim-sulfamethoxazole and amoxicillin-clavulanate in a dog.

Antibiotics are known to be able to cause hypersensitivity reactions through various mechanisms. We present a case of drug-induced immune thrombocytopenia (DITP) and anaphylactic shock occurring simultaneously in a dog after the administration of two classes of antibiotics, namely trimethoprim-sulfamethoxazole (TMP-SMX) and amoxicillin-clavulanate (AMC). The patient recovered completely from DITP on discontinuation of TMP-SMX and the anaphylactic shock caused by AMC was treated with intensive care. DITP is a rare adverse drug reaction (ADR), and anaphylactic shock is a life-threatening ADR. This is the first case report of a dog manifesting two types of hypersensitivity reactions caused by two antibiotics.

Moderate hypothermia attenuates α(1)-adrenoceptor-mediated contraction in isolated rat aorta: the role of the endothelium.

Moderate hypothermia (25-31 °C) may have a significant influence on vascular tone. We investigated the cellular mechanisms by which moderate hypothermia alters α-adrenoceptor-mediated contraction in rat thoracic aortae. Cyclooxygenase inhibition by indomethacin; nitric oxide (NO) synthase inhibition by L-NAME; potassium channel and endothelium-derived hyperpolarizing factor (EDHF) inhibition by glibenclamide and TEA; G protein inhibition by pertussis toxin; α2-adrenergic inhibition by yohimbine; and ß-adrenergic inhibition by propranolol were assessed for their effect on the contractile response to the α1-adrenoceptor agonist phenylephrine (Phe) in combination with moderate hypothermia (25 °C). Moderate hypothermia produced a shift to the right for the Phe concentration-response curves in endothelium-intact (E+) and endothelium-denuded (E-) aortic rings. The maximal response to Phe in E+ rings was significantly decreased (P<0.05) at 25 °C compared to 38 °C, whereas there was no significant difference in E- rings. Hypothermia-induced vasorelaxation in E+ rings was attenuated (P<0.05) following combined pretreatment with L-NAME (10⁻4 M) and indomethacin (10⁻5 M), whereas other inhibitors had no significant effect. Importantly, the addition of TEA to rings that were pretreated with L-NAME and indomethacin exhibited no further attenuation (P>0.05) of hypothermia-induced vasorelaxation. The concentrations of cGMP and cAMP, as measured by radioimmunoassay, were significantly increased (P<0.05) in E+ rings at 25 °C compared to those at 38 °C, whereas there were no significant differences (P>0.05) in E- rings. The present study demonstrated that rat aortic endothelium is stimulated during moderate hypothermia and that the NO-cGMP and prostacyclin (PGI2)-cAMP pathways represent endothelium-dependent mechanisms of hypothermia-induced vasorelaxation. In contrast, EDHF may not be associated with hypothermia-induced vasorelaxation.

Migraine-like headache in a patient with complement 1 inhibitor deficient hereditary angioedema.

We report on an angioedema patient with a genetic defect in complement 1 inhibitor, manifesting migraine-like episodes of headache, effective prophylaxis with Danazol, and triptan for a treatment of acute clinical episode. The patient was 44-yr-old Korean man with abdominal pain and headache, who was brought into the Emergency Department of Seoul National University Hospital, Seoul. He suffered from frequent attacks of migraine-like headache (3-7 per month), pulsating in nature associated with nausea. Severities were aggravated by activity and his headache had shown recent progression with abdominal pain. No remarkable findings were observed on radiologic examination, brain magnetic resonance images and intracranial and extracranial magnetic resonance angiography. Danazol 200 mg every other day was subsequently used. Following administration of Danazol, symptoms showed improvement and the patient was discharged. While taking Danazol, the migraine-like episodes appeared to be prevented for about 2 yr. At the eighth month, he suffered a moderate degree of migraine-like headache; however, administration of naratriptan 2.5 mg resolved his problem. A case of genetic defect of C1-INH deficiency presented with headache episodes, and was controlled by Danazol and triptan. It suggests that pathogenic mechanism of headache in hereditary angioedema may be mediated by the neurogenic inflammatory-like physiology of migraine.

Central nervous system relapses in 3 dogs with B-cell lymphoma.

This report describes cases of central nervous system (CNS) relapse that occurred during chemotherapy in 3 dogs with lymphoma. Diagnosis was made by a combination of clinical signs and cytology of cerebrospinal fluid. The suspected risk factors, clinical features common to the 3 dogs, and treatment options are discussed.

Anti-Inflammatory and Immune Modulatory Effects of Synbio-Glucan in an Atopic Dermatitis Mouse Model.

Many trials have been conducted to treat atopic dermatitis (AD), but these therapies are generally unsuccessful because of their insufficiency or side effects. This study examined the efficacy of ß-glucan derived from oats with fermented probiotics (called Synbio-glucan) on an AD-induced mouse model. For the experiment, Nc/Nga mice were exposed to a house dust mite extract (HDM) to induce AD. The mice were placed in one of four groups: positive control group, Synbio-glucan topical treatment group, Synbio-glucan dietary treatment group, and Synbio-glucan topical + dietary treatment group. The experiment revealed no significant difference in the serum IgE concentration among the groups. Serum cytokine antibody arrays showed that genes related to the immune response were enriched. A significant difference in the skin lesion scores was observed between the groups. Compared to the control group tissue, skin lesions were alleviated in the Synbio-glucan topical treatment group and Synbio-glucan dietary treatment group. Interestingly, almost normal structures were observed within the skin lesions in the Synbio-glucan topical + dietary treatment group. Overall, the ß-glucan extracted from oats and fermented probiotic mixture is effective in treating atopic dermatitis.

Serum Concentration of Inflammatory Cytokines in Dogs with Suspected Acute Pancreatitis.

Acute pancreatitis is an acute inflammatory process in the pancreas that is common in dogs. This study was designed to compare cytokines between healthy dogs and dogs with suspected acute pancreatitis. For the canine cytokine antibody array, three healthy dogs and three dogs with suspected acute pancreatitis were included. Interleukin (IL)-2, IL-6, IL-10, GM-CSF, and TNF-α were not detected in either group based on the results. Conversely, IL-8 (p = 0.035), Monocyte Chemoattractant Protein-1 (MCP)-1 (p = 0.0138), Receptor for Advanced Glycation Endproducts (RAGE) (p = 0.0079), and stem cell factor (SCF) (p = 0.034) were significantly increased in dogs with suspected acute pancreatitis. However, vascular endothelial growth factor (VEGF) (p = 0.6971) did not differ significantly between groups. For the canine serum Enzyme-Linked Immunosorbent Assay (ELISA), eight healthy dogs and eight dogs with suspected acute pancreatitis were included. ELISA revealed that IL-8 (p < 0.0001), MCP-1 (p < 0.0001), RAGE (p = 0.006), and SCF (p = 0.0002) were all significantly upregulated in the experimental group. We confirmed multiple patterns of cytokines in suspected acute pancreatitis of dogs via canine cytokine antibody array using a small quantity of serum. After this procedure, we reevaluated the cytokines, which were significantly increased in dogs with suspected acute pancreatitis, by ELISA, with more samples. Through this study, we confirmed that MCP-1, RAGE, and SCF were newly suggested factors in dogs with suspected acute pancreatitis.

Beta-nerve growth factor gene therapy alleviates pyridoxine-induced neuropathic damage by increasing doublecortin and tyrosine kinase A in the dorsal root ganglion.

Beta-nerve growth factor (ß-NGF) is known to be a major leading cause of neuronal plasticity. To identify the possible action mechanisms of ß-NGF gene therapy for sciatic nerve recovery, experimental dogs were randomly divided into control, pyridoxine, and pyridoxine + ß-NGF groups. We observed chronological changes of morphology in the dorsal root ganglia in response to pyridoxine toxicity based on cresyl violet staining. The number of large neurons positive for cresyl violet was dramatically decreased after pyridoxine intoxication for 7 days in the dorsal root ganglia and the neuron number was gradually increased after pyridoxine withdrawal. In addition, we also investigated the effects of ß-NGF gene therapy on neuronal plasticity in pyridoxine-induced neuropathic dogs. To accomplish this, tyrosine kinase receptor A (TrkA), ßIII-tubulin and doublecortin (DCX) immunohistochemical staining was performed at 3 days after the last pyridoxine treatment. TrkA-immunoreactive neurons were dramatically decreased in the pyridoxine group compared to the control group, but strong TrkA immunoreactivity was observed in the small-sized dorsal root ganglia in this group. TrkA immunoreactivity in the dorsal root ganglia was similar between ß-NGF and control groups. The numbers of ßIII-tubulin- and DCX-immunoreactive cells decreased significantly in the pyridoxine group compared to the control group. However, the reduction of ßIII-tubulin- and DCX-immunoreactive cells in the dorsal root ganglia in the ß-NGF group was significantly ameliorated than that in the pyridoxine group. These results indicate that ß-NGF gene therapy is a powerful treatment of pyridoxine-induced neuropathic damage by increasing the TrkA and DCX levels in the dorsal root ganglia. The experimental protocol was approved by the Institutional Animal Care and Use Committee (IACUC) of Seoul National University, South Korea (approval No. SNU-060623-1, SNU-091009-1) on June 23, 2006 and October 9, 2009, respectively.

The Efficacy of Shinbaro for the Preventive Treatment of Migraine: A Pilot Study.

OBJECTIVE: To investigate the therapeutic potential and efficacy of Shinbaro, an herbal medication for inflammatory diseases and bone disorders, as a preventive treatment of migraine. METHODS: In this prospective, interventional, single-arm, pre-post study, 37 migraine patients took 600mg bid of Shinbaro for 12 weeks. At 4-week intervals, the migraine frequency and the rescue medications frequency were measured from each patient's headache diary. The modified Migraine Disability Assessment (MIDAS) questionnaires to assess migraine associated disabilities were also completed at each visit. The serum calcitonin gene-related peptide (CGRP) concentrations before and after 12 weeks of Shinbaro administration were compared. RESULTS: The monthly migraine frequency was significantly reduced from 20.5 days at baseline to 16.4 days at week 12 (P =0.003), and 22% of the participants showed ≥ 50% reduction. The frequency reduction was observed by week 4 (P =0.035) and continuously occurred through week 8 (P =0.001) and week 12 (P =0.003). The rescue medications frequency also decreased significantly from 17.4 days at baseline to 13.2 days at week 12 (P =0.035). Lastly, the serum CGRP concentration dropped from 434.6 pg/mL at baseline to 371.4 pg/mL at week 12, which was statistically significant (P <0.001). CONCLUSIONS: Shinbaro demonstrated prophylactic effects in migraine patients, significantly reducing their mean migraine frequency, rescue medications frequency, and the serum CGRP concentration after 12 weeks of treatment. This study is registered in Clinical Research Information Service, Seoul National University Hospital Clinical Research Institute (IRB No. 1604-138-758).

Effect of a poloxamer-based thermosensitive gel on rotator cuff repair in a rabbit model: a controlled laboratory study.

BACKGROUND: A common complication after rotator cuff repair is postoperative stiffness, which can be reduced by a simple application of an anti-adhesive agent. However, anti-adhesive agents may affect rotator cuff healing by preventing fibrosis. This experimental animal study evaluated the effect of the application of a poloxamer-based thermosensitive anti-adhesive gel and its influence on the healing of an acute rotator cuff repair in a rabbit model. METHODS: Acute rotator cuff repair (supraspinatus tendon) was performed using a transosseous suturing method. One shoulder on a randomly selected side was treated with a local application of the anti-adhesive agent (applied side), and saline was applied to the contralateral side (control side). Biomechanical testing and histological analyses were performed at 4 and 8 weeks postoperatively. Eight rabbits were included for each testing and time point, for a total of 32 rabbits. RESULTS: The failure load at 4 weeks was lower in the experimental group (95.2 ± 19.6 N vs. 110.0 ± 20.5 N; P = 0.017). Conversely, at 8 weeks, the failure load was higher in the experimental group (148.3 ± 16.2 N) than in the control group (122.4 ± 16.9 N; P = 0.002). Histological analyses revealed no statistically significant differences in the tendon maturing scores at 4 and 8 weeks between the two groups (all P > 0.05). The thickness of the fibrosis between the rotator cuff tendon and deltoid was thinner in the experimental group at both time points (0.50 ± 0.25 vs. 1.27 ± 0.47; P = 0.002 at 4 weeks, and 0.37 ± 0.35 vs. 1.39 ± 0.50; P = 0.003 at 8 weeks). CONCLUSIONS: Application of an anti-adhesive agent in this rotator cuff model confirmed the agent's effectiveness at reducing fibrosis in the subacromial space. The healing of the tendon showed interesting results, as the experimental group had poorer biomechanical strength at 4 weeks but superior strength at 8 weeks.

Pyridoxine induced neuropathy by subcutaneous administration in dogs.

To construct a sensory neuropathy model, excess pyridoxine (150 mg/kg s.i.d.) was injected subcutaneously in dogs over a period of 7 days. During the administrations period, the dogs experienced body weight reduction and proprioceptive loss involving the hindquarters. After pyridoxine administration was completed, electrophysiological recordings showed that the M wave remained at a normal state, but the H-reflex of the treated dogs disappeared at 7 days. The dorsal funiculus of L(4) was disrupted irregularly in the axons and myelin with vacuolation. The dorsal root ganglia of L(4), and sciatic and tibial nerves showed degenerative changes and vacuolation. However, the lateral and ventral funiculi of L(4) showed a normal histopathologic pattern. Although this subcutaneous administration method did not cause systemic toxicity and effectively induced sensory neuropathy, this study confirmed the possibility of producing a pyridoxine-induced sensory neuropathy model in dogs with short-term administration.