Suspected malnutrition-induced reversible feline skin fragility syndrome in a cat with congenital axial deformities.

A stray cat, an intact female Japanese domestic shorthair cat of unknown age (suspected to be a young adult), was rescued. The cat was lethargic and thin and had marked skin fragility, delayed wound healing without skin hyperextensibility, and hind limb proprioceptive ataxia and paresis. Survey radiography, computed tomography, and magnetic resonance imaging revealed congenital vertebral anomalies, including thoracolumbar transitional vertebrae, scoliosis resulting from a thoracic lateral wedge-shaped vertebra, and a kinked tail, and a dilated spinal cord central canal. Through nutritional support, the cat's general condition normalized, followed by a gradual and complete improvement of skin features. Whole-genome sequencing was completed; however, no pathogenic genetic variant was identified that could have caused this phenotype, including congenital scoliosis. A skin biopsy obtained 7 y after the rescue revealed no remarkable findings on histopathology or transmission electron microscopy. Based on clinical course and microscopic findings, malnutrition-induced reversible feline skin fragility syndrome (FSFS) was suspected, and nutritional support was considered to have improved the skin condition. Key clinical message: This is the second reported case of presumed malnutrition-induced reversible FSFS and was accompanied by long-term follow-up.

Syndrome de fragilité cutanée réversible induit par la malnutrition soupçonné chez un chat avec des difformités axiales congénitales. Un chat errant, une femelle intacte de race japonaise à poil court et d'âge inconnu (suspecté être une jeune adulte), a été secourue. La chatte était léthargique et maigre, et avait une fragilité marquée de la peau, un retard dans la guérison de plaies sans hyperextensibilité de la peau, et une ataxie proprioceptive et parésie des membres postérieurs. Des radiographies, un examen par tomodensitométrie, et de l'imagerie par résonnance magnétique ont révélé des anomalies congénitales des vertèbres, incluant des vertèbres transitionnelles thoraco-lombaires, une scoliose résultant d'une vertèbre thoracique en forme de coin, une queue pliée, et un canal central de la moelle épinière dilaté. Grâce à un soutien nutritionnel, la condition générale du chat s'est stabilisée, suivi d'une amélioration graduelle et complète des caractéristiques de la peau. Le séquençage du génome complet a été effectué; toutefois, aucune variation génétique pathogénique n'a été identifiée qui aurait pu causer ce phénotype, incluant la scoliose congénitale. Une biopsie cutanée obtenue 7 j après le sauvetage n'a révélé aucune trouvaille spéciale à l'histopathologie ou par microscopie électronique à transmission. Basé sur le déroulement clinique et l'examen microscopique, le syndrome de fragilité cutanée réversible félin induit par la malnutrition (FSFS) était suspecté, et le soutien nutritionnel a été considéré comme ayant amélioré la condition cutanée.Message clinique clé :Ce cas est le deuxième cas rapporté de FSFS induit par la malnutrition soupçonné et a fait l'objet d'un suivi à long terme.(Traduit par Dr Serge Messier).

Apple polyphenols exhibits chondroprotective changes of synovium and prevents knee osteoarthritis.

Apple polyphenols (AP) have strong antioxidant and anti-inflammatory properties. We examined the effects of AP on the progression of osteoarthritis (OA) AP was administered to surgically-induced OA model rats for 4 or 8 weeks. This treatment suppressed inflammation and oxidative stress in the synovium, resulting in a decrease in the OA severity score, and the expression of tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-13 in the synovium. It was suggested that long-term administration of AP may be effective for the treatment of OA. In addition, superoxide dismutase (SOD) activity was enhanced in serum samples by AP. AP or its constituent procyanidin B2 (PC) were added to HIG-82 synoviocytes. The results showed that AP enhanced cell proliferation and hyaluronan production. This indicates that AP may improve synovial conditions in OA and suppress OA progression. These effects may be attributed to the antioxidant and anti-inflammatory properties of AP.

Shark protein improves bone mineral density in ovariectomized rats and inhibits osteoclast differentiation.

OBJECTIVES: Fish proteins are potential sources of natural medicines and food additives. There are many studies being performed to develop underutilized fish proteins. Therefore, the aim of this study was to determine how shark protein functions as a dietary supplement for bone health. METHODS: Three groups of ovariectomized (OVX) rats were fed different diets containing 20% casein protein, 20% shark protein, or 20% cod protein for 4 wk. Bone mineral density of the right femur was measured by dual-energy x-ray absorptiometry and quantitative computed tomography. Furthermore, we prepared low-molecular-weight peptides from shark protein using protease for in vitro studies. Calcitriol was added to bone marrow cells and the receptor activator of the nuclear factor-κB ligand was added to RAW264 cells. After 7 d, the number of tartrate-resistant acid phosphatase-positive cells was counted. RESULTS: In the shark protein-fed group, bone mineral density of the femur epiphysis was higher than that of the casein protein-fed group. In particular, the shark protein-fed group showed an increase in bone mineral density, represented mainly by trabecular bone. Shark protein hydrolysates inhibited osteoclast formation in bone marrow cells and RAW264 cells. CONCLUSIONS: These results suggest that shark protein might suppress the bone loss caused by estrogen deficiency through the suppression of osteoclast formation.

Hyperdry human amniotic membrane is useful material for tissue engineering: physical, morphological properties, and safety as the new biological material.

Human amniotic membrane (AM) has been used widely as graft biomaterial for a variety of clinical applications. But, there are some persistent problems related to the preparation, storage, and sterilization. To resolve these problems, we developed hyperdry AM (HD-AM) using far-infrared rays, depression of air, and microwaves and then sterilized by γ-ray irradiation. To elucidate the benefit of HD-AM as biological materials, compare with the physical and histological properties of HD-AM with a freeze-dried AM (FD-AM) as typical freeze-dried methods, evaluate the safety of HD-AM in vivo experiment used nude mice, and demonstrate the feasibility of HD-AM transplant in pterygium. The water permeability and the sieving coefficient of HD-AM were significantly lower than that of FD-AM. HD-AM has kept the morphological structure of epithelium and connective tissues. At 18 months after transplanted, single and multilayers of HD-AM in the intraperitoneal cavity was degraded without any infiltrated cells. For clinical treatment, recurrence of pterygium and regrowth of the subconjunctival fibrosis were not observed during the 6-month follow-up periods after the surgery. It was proposed that HD-AM was a safe and effective new biological material for clinical use including treatment for recurrent pterygium.

[Granulocyte-colony stimulating factor-producing urothelial carcinoma of right renal pelvis : a case report].

A 78-year-old female patient with fever and general malaise was referred to our hospital. Laboratory examination showed the marked elevation of leukocyte and serum granulocyte-colony stimulating factor (GCSF) concentration without any infectious sign. A computed tomography scan demonstrated irregular enhanced mass of the right kidney with liver metastasis. The pathological findings of the needle biopsy was high-grade urothelial cancer with positive staining for G-CSF antibody. Systemic chemotherapy with gemcitabine and cisplatin was administered. The patient showed a partial response and the serum G-CSF level was normalized after 1 course of chemotherapy. After four courses of chemotherapy, the extent of liver metastasis increased and the G-CSF concentration became elevated. Although combined chemotherapy with paclitaxel and gemcitabine was administered, the patient died 7 months after her first visit.

Ingestion of proteoglycan fraction from shark cartilage increases serum inhibitory activity against matrix metalloproteinase-9 and suppresses development of N-nitrosobis(2-oxopropyl)amine-induced pancreatic duct carcinogenesis in hamster.

A water extract of shark cartilage was fractionated into acidic and basic fractions by preparative isoelectric focusing on the basis of the amphoteric nature of samples. The acidic fraction was further fractionated into ethanol-soluble and -precipitate fractions. After the carcinogenesis treatment using N-nitrosobis(2-oxopropyl)amine, hamsters received a diet containing each fraction or purified chondroichin sulfate to give 0.4% (w/w) for 50 days. Only administration of the acidic ethanol-precipitate-fraction-containing diet significantly increased serum inhibitory activity against matrix metalloproteinase (MMP)-9 and reduced the number of adenocarcinomas in the pancreatic duct. The active fraction predominantly consisted of chondroichin sulfate-containing proteoglycan. However, the purified chondroichin sulfate had no significant activity. These results suggest that the protein moiety of the proteoglycan might be involved in the increase of serum inhibitory activity against MMP-9 and suppression of pancreatic carcinogenesis in hamster.

IL-1beta stimulates activin betaA mRNA expression in human skin fibroblasts through the MAPK pathways, the nuclear factor-kappaB pathway, and prostaglandin E2.

During mouse skin wound healing, mRNAs encoding IL-1, activins, and TGF-ßs significantly increased. To elucidate involvement of IL-1 in the regulation of activins and related factors in the wounded skin, human foreskin fibroblasts were stimulated with IL-1ß, and levels of mRNAs encoding activins, TGF-ßs, and follistatin family proteins were examined by quantitative real-time PCR. IL-1ß increased activin ßA (INHBA) and follistatin (FST) mRNA expression within 6 h. A p38 MAPK inhibitor, SB202190, a MAPK/ERK kinase inhibitor, U0126, and an nuclear factor κB pathway inhibitor, SC-514, significantly suppressed the IL-1ß-stimulated INHBA and FST mRNA expression. A prostaglandin-endoperoxide synthase inhibitor indomethacin, a potent inhibitor of prostaglandin E(2) (PGE(2)) synthesis, also significantly suppressed the IL-1ß-stimulated INHBA but not FST mRNA expression. Furthermore, stimulation of fibroblasts with PGE(2) significantly increased INHBA mRNA. The PGE(2)-induced INHBA mRNA expression was significantly suppressed by U0126 and a protein kinase C inhibitor, Gö 6983. Although IL-1ß stimulated FST mRNA in an acute phase, long-term exposure of fibroblasts to IL-1ß revealed time-dependent stimulatory and inhibitory effects of IL-1ß on FST mRNA expression. On the other hand, coculture with keratinocytes significantly increased INHBA mRNA expression in dermal equivalents. In summary, the present study indicates that the p38 MAPK, the MAPK/ERK kinase, the nuclear factor κB pathway, and PGE(2) mediate the effects of IL-1ß on INHBA mRNA expression. Furthermore, it is indicated that keratinocyte-derived factor of factors stimulate INHBA mRNA expression during wound healing.

Change in decorin during aging of rat placenta.

By immunohistochemistry, with or without chondroitinases, decorin was found to be distributed in the extracellular matrix of chorionic villi and amnia. The strength of staining intensified with increasing gestational age. Decorin was isolated from the placenta of 13- to 20-day-old pregnant rats and identified by Western blotting, using an antidecorin core protein antibody. The molecular weight of decorin is approximately 100 kDa, whereas the respective figures for the core protein treated with chondroitinase (chase) ABC and with chase B are approximately 40 kDa and 43 kDa. The difference in the molecular weight between the core protein with chase ABC and B suggests that the glycosaminoglycan (GAG)- base structure on the core protein was chondroitin sulfate (CS) without dermatan sulfate (DS). The decorin content and the proportion of CS to DS in GAG increased with age. We concluded that the age-related changes in the GAG chain may be related to specific functional properties and may have a crucial role in placental tissue organization.

Immuno-magnetic separation and agar layer methods for the isolation of freeze-injured Yersinia enterocolitica O:8 from water.

To develop an effective method to isolate an injured pathogenic Yersinia enterocolitica O:8 organism from environmental samples, we compared the isolation of freeze-injured and non-injured Y. enterocolitica O:8 and found that the isolation was more successful when immuno-magnetic separation (IMS) with anti-Y. enterocolitica O:8 antibody was used. Plating onto cefsulodin-irgasan-novobiocin (CIN) agar and Virulent Yersinia enterocolitica (VYE) agar by means of the agar layer method was found to be effective in isolating the injured cells. The alkali treatment which is generally used for selective detection of Yersinia organism failed to isolate freeze-injured pathogenic Y. enterocolitica O:8 cells. Recovery methods without using the alkali treatment were superior for detecting freeze-injured Y. enterocolitica O:8. Our results demonstrate that the IMS and the agar layer methods should be used to isolate injured pathogenic Yersinia organisms from environmental samples such as water.

Human leukocyte-derived arginine aminopeptidase. The third member of the oxytocinase subfamily of aminopeptidases.

In this study we report the cloning and characterization of a novel human aminopeptidase, which we designate leukocyte-derived arginine aminopeptidase (L-RAP). The sequence encodes a 960-amino acid protein with significant homology to placental leucine aminopeptidase and adipocyte-derived leucine aminopeptidase. The predicted L-RAP contains the HEXXH(X)18E zinc-binding motif, which is characteristic of the M1 family of zinc metallopeptidases. Phylogenetic analysis indicates that L-RAP forms a distinct subfamily with placental leucine aminopeptidase and adipocyte-derived leucine aminopeptidase in the M1 family. Immunocytochemical analysis indicates that L-RAP is located in the lumenal side of the endoplasmic reticulum. Among various synthetic substrates tested, L-RAP revealed a preference for arginine, establishing that the enzyme is a novel arginine aminopeptidase with restricted substrate specificity. In addition to natural hormones such as angiotensin III and kallidin, L-RAP cleaved various N-terminal extended precursors to major histocompatibility complex class I-presented antigenic peptides. Like other proteins involved in antigen presentation, L-RAP is induced by interferon-gamma. These results indicate that L-RAP is a novel aminopeptidase that can trim the N-terminal extended precursors to antigenic peptides in the endoplasmic reticulum.