Anti-inflammatory Dexamethasone Research Articles

Development and characterization of dexamethasone nanodispersion for the effective treatment of diabetic retinopathy

Diabetic retinopathy is the most common complication of diabetes and remains the leading cause of vision loss worldwide. The potent glucocorticoid based anti-inflammatory drug dexamethasone (DEX) chosen for the present work is long-acting with half-life of 37–72 h extensively metabolized in to 6-hydroxy-dexamethasone (6-OH-DEX). The present work aimed to develop dexamethasone loaded nanodispersion (DEX-ND) by improving its solubility, half-life, and bioavailability in biological system thereby this formulation may be afforded economically. With the concept that polymeric surfactant improves the solubility of challenging water insoluble drug the present work has been hypothesized to improve its solubility using polyvinyl pyrrolidone (PVP-K30) polymer and polysorbate 80 (Tween 80) hydrophilic non-ionic surfactant, thereby the bioavailability is expected to get enhanced. By varying the PVP K30 and Tween 80 concentrations three different formulations were developed. The developed DEX-ND was further characterized for its compatibility, particle size, zeta potential, morphology, and in vitro release behavior. The results of Fourier transform infrared spectrometric analysis indicate the compatibility nature of DEX-ND along with other excipients/drug used in the formulation. The developed formulations showed spherical morphology, particle size ranging from 550.46 ± 107.82 to 3560 ± 284.29 nm, zeta potential ranging from −29.23 ± 1.09 to −7.793 ± 1.01 mV. The amount of DEX present in the DEX-NDs was found to be 0.95–3.93 mg. The in vitro release studies as performed by dialysis bag method showed a sustained release pattern. The results of ex vivo corneal permeation studies indicates that the developed DEX- NDs has some exposure to the posterior segment of the eye.

Nanofiber Hydrogel Drug Delivery System for Prevention of Postsurgical Intestinal Adhesion.

Intestinal adhesion is one of the complications that occurs more frequently after abdominal surgery. Postsurgical intestinal adhesion (PIA) can lead to a series of health problems, including abdominal pain, intestinal obstruction, and female infertility. Currently, hydrogels and nanofibrous films as barriers are often used for preventing PIA formation; however, these kinds of materials have their intrinsic disadvantages. Herein, we developed a dual-structure drug delivery patch consisting of poly lactic-co-glycolic acid (PLGA) nanofibers and a chitosan hydrogel (NHP). PLGA nanofibers loaded with deferoxamine mesylate (DFO) were incorporated into the hydrogel; meanwhile, the hydrogel was loaded with anti-inflammatory drug dexamethasone (DXMS). The rapid degradation of the hydrogel facilitated the release of DXMS at the acute inflammatory stage of the early injury and provided effective anti-inflammatory effects for wound sites. Moreover, PLGA composite nanofibers could provide sustained and stable release of DFO for promoting the peritoneal repair by the angiogenesis effects of DFO. The in vivo results indicated that NHP can effectively prevent PIA formation by restraining inflammation and vascularization, promoting peritoneal repair. Therefore, we believe that our NHP has a great potential application in inhibition of PIA.

CYSTITIS IN MIX BREED DOG

Cystitis is an inflammation of the vesica urinaria. A male mixed breed dog named Max, 3 years old and weighing 18.68 kg, has stranguria and dysuria with a small volume of urine, and hematuria. The purpose of this report is to discuss the incidence of cystitis in male mixed breed dogs in performing diagnostic measures as well as appropriate treatment and therapy for the dog. Clinical examination showed pulse frequency, heart rate, respiratory, and body temperature within the normal range. Abdominal palpation revealed signs of pain. Routine hematology analysis revealed struvite and tyrosine crystals. Urinalysis showed elevated leucocytes and post-renal proteinuria. Urine culture examination revealed Staphylococcus sp. Ultrasonography examination showed thickening of the vesical urinary mucous. Based on findings, the dog case was diagnosed with cystitis. Treatment included antibiotics amoxicillin, anti-inflammatory drug dexamethasone, and additional herbal medicine kejibeling. The case dog showed improvement after seven days of treatment with no symptoms such as haematuria. To minimise the recurrence of cystitis in dogs, Urinary Care feed and ad libitum watering can be done to help dissolve crystals in the vesica urinaria.

STRUVITE CRYSTAL UROLITHIASIS IN A 2 YEAR OLD CASTRATED MALE CAT

Urolithiasis, kidney failure, urinary tract infections are examples of disorders of the urinary tract that often become problems in cats. Urolithiasis is a medical term to describe the presence of stones or crystals known as “urolith” in the urinary tract. Inappropriate composition and feeding methods can cause nutritional imbalances in the cat's body, which can affect the acidity level (pH) of urine, urine volume and urine concentration which can cause the formation of excessive minerals in the urine. The aim of writing this article is to provide information regarding the treatment of crystal urolithiasis in local cats. A male cat named Goblin, has been castrated, has colored hair orange with body weight 5.3 kg, experiencing difficulty urinating since 3 weeks, excreting a small volume of urine, and blood in the urine. On physical examination the cat always curled up and felt pain when palpation was carried out abdominal part. The results of the cat's blood test showed leukocytosis, lymphocytosis, thrombocytopenia, and RDW CV increased and PCT decreased. The results of the cat's urinalysis showed presence of leukocytes +2, Protein +1, pH 8.0, specific gravity 1.030, Calcium +1, Microalbumin +1.Sediment test results also found the presence of deposits of magnesium ammonium phosphate crystal particles (struvite crystals).Results of urine culture examination bacteria were foundStaphylococcus sp. Ultrasound results showed enlargement of the left kidney and deposits of hyperechoic particles (crystals) accompanied by enlargement of the uterine sac. The cat was diagnosed with urolithiasis with a fausta prognosis. The cat was treated by installing a 4Fr/1.3x130mm urinary catheter and flushing using 0.9% physiological NaCl to make it easier for the cat to urinate. The therapy given is the antibiotic ciprofloxacin hcl 5 mg/kg BW s500 mg preparation with a dose of 50 mg/kg BW per oral (PO) administered 2 times a day for seven days, administering the anti-inflammatory dexamethasone 0.5 mg with a dose of 1 mg/kg BW PO and given 2 times a day for four days, and kejibeling herbal medicine 1 tablet times a day for seven days. Cats are also given feed therapy in the form of Royal Canin Urinary S/O for 3 months. Evaluation of the cat's condition improved after therapy for 7 days. There is a need to educate clients regarding cat care, feeding and drinking water. Therefore, the cat's feed in cases must be replaced by providing urinary therapy feed.

Colon-targeted hydroxyethyl starch-curcumin microspheres with high loading capacity ameliorate ulcerative colitis via alleviating oxidative stress, regulating inflammation, and modulating gut microbiota

Curcumin (CUR) is a natural polyphenol that holds promise for treating ulcerative colitis (UC), yet oral administration of CUR exhibits limited bioavailability and existing formulations for oral delivery of CUR often suffer from unsatisfactory loading capacity. This study presents hydroxyethyl starch-curcumin microspheres (HC-MSs) with excellent CUR loading capacity (54.52 %), and the HC-MSs can further encapsulate anti-inflammatory drugs dexamethasone (DEX) to obtain a combination formulation (DHC-MSs) with high DEX loading capacity (19.91 %), for combination therapy of UC. The microspheres were successfully engineered, retaining the anti-oxidative and anti-inflammatory activities of parental CUR and demonstrating excellent biocompatibility and controlled release properties, notably triggered by α-amylase, facilitating targeted drug delivery to inflamed sites. In a mouse UC model induced by dextran sulfate sodium, the microspheres effectively accumulated in inflamed colons and both HC-MSs and DHC-MSs exhibited superior therapeutic efficacy in alleviating UC symptoms compared to free DEX. Moreover, mechanistic exploration uncovered the multifaceted therapeutic mechanisms of these formulations, encompassing anti-inflammatory actions, mitigation of spleen enlargement, and modulation of gut microbiota composition. These findings underscore the potential of HC-MSs and DHC-MSs as promising formulations for UC, with implications for advancing treatment modalities for various inflammatory bowel disorders.

Biomaterial-mediated intracellular control of macrophages for cell therapy in pro-inflammatory and pro-fibrotic conditions

Macrophages are key modulators of all inflammatory diseases and essential for their resolution, making macrophage cell therapy a promising strategy for regenerative medicine. However, since macrophages change rapidly in response to microenvironmental cues, their phenotype must be controlled post-administration. We present a tunable biomaterial-based strategy to control macrophages intracellularly via small molecule-releasing microparticles. Poly(lactic-co-glycolic acid) microparticles encapsulating the anti-inflammatory and anti-fibrotic drug dexamethasone were administered to macrophages in vitro, with uptake rates controlled by different loading regimes. Microparticle dose and dexamethasone content directly affected macrophage phenotype and phagocytic capacity, independent of particle content per cell, leading to an overall pro-reparative, anti-inflammatory, anti-fibrotic phenotype with increased phagocytic and ECM degrading functionality. Intracellularly controlled macrophages partially maintained this phenotype in vivo in a murine pulmonary fibrosis model, with more prominent effects in a pro-fibrotic environment compared to pro-inflammatory. These results suggest that intracellular control using biomaterials has the potential to control macrophage phenotype post-administration, which is essential for successful macrophage cell therapy.

DT-13 attenuates inflammation by inhibiting NLRP3-inflammasome related genes in RAW264.7 macrophages

Plant derived saponins or other glycosides are widely used for their anti-inflammatory, antioxidant, and anti-viral properties in therapeutic medicine. In this study, we focus on understanding the function of the less known steroidal saponin from the roots of Liriope muscari L. H. Bailey – saponin C (also known as DT-13) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in comparison to the well-known saponin ginsenoside Rk1 and anti-inflammatory drug dexamethasone. We proved that DT-13 reduces LPS-induced inflammation by inhibiting nitric oxide (NO) production, interleukin-6 (IL-6) release, cycloxygenase-2 (COX-2), tumour necrosis factor-alpha (TNF-α) gene expression, and nuclear factor kappa-B (NFκB) translocation into the nucleus. It also inhibits the inflammasome component NOD-like receptor family pyrin domain containing protein 3 (NLRP3) regulating the inflammasome activation. This was supported by the significant inhibition of caspase-1 and interleukin-1 beta (IL-1β) expression and release. This study demonstrates the anti-inflammatory effect of saponins on LPS-stimulated macrophages. For the first time, an in vitro study shows the attenuating effect of DT-13 on NLRP3-inflammasome activation. In comparison to the existing anti-inflammatory drug, dexamethasone, and triterpenoid saponin Rk1, DT-13 more efficiently inhibits inflammation in the applied cell culture model. Therefore, DT-13 may serve as a lead compound for the development of new more effective anti-inflammatory drugs with minimised side effects.

Dexamethasone nanomedicines with optimized drug release kinetics tailored for treatment of site-specific rheumatic musculoskeletal diseases

The application of polymer-based drug delivery systems is advantageous for improved pharmacokinetics, controlled drug release, and decreased side effects of therapeutics for inflammatory disease. Herein, we describe the synthesis and characterization of linear N-(2-hydroxypropyl)methacrylamide-based polymer conjugates designed for controlled release of the anti-inflammatory drug dexamethasone through pH-sensitive bonds. The tailored release rates were achieved by modifying DEX with four oxo-acids introducing reactive oxo groups to the DEX derivatives. Refinement of reaction conditions yielded four well-defined polymer conjugates with varied release profiles which were more pronounced at the lower pH in cell lysosomes. In vitro evaluations in murine peritoneal macrophages, human synovial fibroblasts, and human peripheral blood mononuclear cells demonstrated that neither drug derivatization nor polymer conjugation affected cytotoxicity or anti-inflammatory properties. Subsequent in vivo tests using a murine arthritis model validated the superior anti-inflammatory efficacy of the prepared DEX-bearing conjugates with lower release rates. These nanomedicines showed much higher therapeutic activity compared to the faster release systems or DEX itself.

TREATMENT OF BULBUS OCULI DEXTRA PROLAPSE IN MIX POM DOGS

Prolapse of the bulbus oculi is a condition where the eyeball protrudes from the eye socket, which occurs due to impact, blunt trauma, fights or tumors. A Mix Pom purebred dog, named Koko, male, 7 years old, 5.21 kg body weight and brown hair color, complained of the right eyeball protruding from the eye socket since two days. The purpose of writing this case report is to describe the process of lifting the eyeball by cutting the tissue and the nerves inside it using the enucleation technique. From physical examination and clinical signs, the case dog was diagnosed with prolapse of the dextra bulbus oculi with a fausta prognosis. Case dogs were treated with bulbus oculi enucleation surgery, which is a surgical procedure by lifting the eyeball from the eye socket. The surgery was performed under a combination of xylazine and ketamine general anesthesia. Postoperative case dogs were given cefotaxime antibiotics at a dose of 20 mg/kg body weight for two days and followed by oral antibiotic cefixime trihydrate at a dose of 10 mg/kg body weight for five days. Anti-inflammatory in the form of tolfenamic acid with a dose of 4 mg/kg body weight intramuscularly for two days and followed by oral anti-inflammatory dexamethasone tablets 0.25 mg/kg body weight (2 x daily) for five days. The results of the operation showed wound healing on the 10th day, which was indicated by the stitches that had dried and merged, and the dog was active again. Advice that can be given is that a dog suffering from bulbus oculi prolapse must be immediately acted upon, so as not to worsen the dog's condition and to prevent various complications, one of which is miasis.

Dexamethasone phosphate and penetratin co-eluting contact lenses: a strategy to enhance ocular drug permeability

Contact lenses (CLs) have been suggested as drug delivery platforms capable of increasing the drug residence time on the cornea and therefore its bioavailability. However, when targeting the posterior segment of the eye, the drug released from CLs still encounters the barrier effect of the ocular tissues, which considerably reduces the efficacy of administration. This work aims at the development of CLs able to simultaneously deliver an anti-inflammatory drug (dexamethasone sodium phosphate) and a cell-penetrating peptide (penetratin), the latter acting as a drug carrier across the tissues. Hydroxyethyl methacrylate (HEMA)-based hydrogels were functionalized with acrylic acid (AAc) and/or aminopropyl methacrylamide (APMA) to serve as CL materials with increased affinity for the drug and peptide. APMA-functionalized hydrogels sustained the dual release for 8 h, which is compatible with the wearing time of daily CLs. Hydrogels demonstrated suitable light transmittance, swelling capacity and in vitro biocompatibility. The anti-inflammatory activity of the drug was not compromised by the presence of the peptide nor by sterilization. The ocular distribution of the drug after 6 h of CL wearing was evaluated in vivo in rabbits and revealed that the amount of drug in the cornea and aqueous humor significantly increased when the drug was co-delivered with penetratin.

Flexible multifunctional titania nanotube array platform for biological interfacing

The current work presents a novel flexible multifunctional platform for biological interface applications. The use of titania nanotube arrays (TNAs) as a multifunctional material is explored for soft-tissue interface applications. In vitro biocompatibility of TNAs to brain-derived cells was first examined by culturing microglia cells—the resident immune cells of the central nervous system on the surface of TNAs. The release profile of an anti-inflammatory drug, dexamethasone from TNAs-on-polyimide substrates, was then evaluated under different bending modes. Flexible TNAs-on-polyimide sustained a linear release of anti-inflammatory dexamethasone up to ~11 days under different bending conditions. Finally, microfabrication processes for patterning and transferring TNA microsegments were developed to facilitate structural stability during device flexing and to expand the set of compatible polymer substrates. The techniques developed in this study can be applied to integrate TNAs or other similar nanoporous inorganic films onto various polymer substrates.Impact statementTitania nanotube arrays (TNAs) are highly tunable and biocompatible structures that lend themselves to multifunctional implementation in implanted devices. A particularly important aspect of titania nanotubes is their ability to serve as nano-reservoirs for drugs or other therapeutic agents that slowly release after implantation. To date, TNAs have been used to promote integration with rigid, dense tissues for dental and orthopedic applications. This work aims to expand the implant applications that can benefit from TNAs by integrating them onto soft polymer substrates, thereby promoting compatibility with soft tissues. The successful direct growth and integration of TNAs on polymer substrates mark a critical step toward developing mechanically compliant implantable systems with drug delivery from nanostructured inorganic functional materials. Diffusion-driven release kinetics and the high drug-loading efficiency of TNAs offer tremendous potential for sustained drug delivery for scientific investigations, to treat injury and disease, and to promote device integration with biological tissues. This work opens new opportunities for developing novel and more effective implanted devices that can significantly improve patient outcomes and quality of life.Graphical abstract

Sustained Release of Dexamethasone from 3D-Printed Scaffolds Modulates Macrophage Activation and Enhances Osteogenic Differentiation.

Enhancing osteogenesis via modulating immune cells is emerging as a new approach to address the current challenges in repairing bone defects and fractures. However, much remains unknown about the crosstalk between immune cells and osteolineage cells during bone formation. Moreover, biomaterial scaffold-based approaches to effectively modulate this crosstalk to favor bone healing are also lacking. This study is the first to investigate the interactions between macrophages and mesenchymal stem cells (MSCs) in co-cultures with the sustained release of an anti-inflammatory and pro-osteogenesis drug (dexamethasone) from three-dimensional (3D)-printed scaffolds. We successfully achieved the sustained release of dexamethasone from polycaprolactone (PCL) by adding the excipient-sucrose acetate isobutyrate (SAIB). Dexamethasone was released over 35 days in the 17-163 nM range. The osteogenic differentiation of MSCs was enhanced by M1 macrophages at early time points. The late-stage mineralization was dominated by dexamethasone, with little contribution from the macrophages. Besides confirming BMP-2 whose secretion was promoted by both dexamethasone and M1 macrophages as a soluble mediator for enhanced osteogenesis, IL-6 was found to be a possible new soluble factor that mediated osteogenesis in macrophage-MSC co-cultures. The phenotype switching from M1 to M2 was drastically enhanced by the scaffold-released dexamethasone but only marginally by the co-cultured MSCs. Our results offer new insight into macrophage-MSC crosstalk and demonstrate the potential of using drug-release scaffolds to both modulate inflammation and enhance bone regeneration.

STRICTURE AND MEGAESOPHAGEAL IN LOCAL CATS

The esophagus is part of the digestive system which is between the oropharynx and the stomach of the animal. The condition characterized by reduced or absent esophageal motility is called megaesophagus. Megaesophagus causes accumulation of ingesta, dilatation of the esophageal lumen, and regurgitation of feed (which is often mistaken for vomiting by cat owners). The aim of this study was to treat a female cat, 9 months old, weighing 3.2 kg was diagnosed with stricture and megaesophagus. The cat was brought in with vomiting several times after eating since seven days after the ovariohysterectomy surgery. Clinical examination showed that the cat experienced regurgitation and increased respiratory rate. Supporting examinations such as a complete hematological examination were carried out with the result leukocytosis. Radiographic examination in the form of x-rays show that there is stricture and dilatation in the esophageal area. Cats are handled by feeding them with an upright position for about 20-30 minutes. Treatment is by administering the antibiotic cefotaxime sodium (Cefotaxim sodium®, PT. Dankos Farma, Jakarta, Indonesia) intravenously at a dose of 20 mg/kg IV two times a day, administering the anti-inflammatory drug Dexamethasone at a dose of 0.125 mg/kg by injection, administering antiemetic drugs Ondansetron 0.2 mg/kgBW intravenously and Ranitidine HCl at a dose of 2 mg/kgBW intravenously. The cat's condition did not show any improvement during the treatment which was carried out after 7 days, therefore it was decided that euthanasia would be the best choice.

UNILATERAL RHINITIS AND HEMOBARTONELLA FELIS INFECTION IN DOMESTIC CATS WITH A HISTORY OF CHRONIC KIDNEY DISEASE

Rhinitis is an inflammation of the mucous membranes of the nasal cavity, which can arise from a number of intranasal or systemic disorders. Hemobartonella felis is a gram-negative intracellular bacterium that attacks cat's erythrocytes. This treatment aims to discuss diagnostic and treatment techniques for rhinitis and Hemobartonellosis infection in cat with kidney failure. The animal is a local cat with a history of kidney failure, female, 6 years old and weighing 2.7 kg. The owner came with complaints of a serous discharge in the right nasal cavity and occasional sneezing. The cat has decreased appetite since 6 months and looks weak. Clinical examination showed swelling of the right mandibular lymph nodes and inspection of the oral cavity found gingivitis, tartar, and halitosis. Routine hematological examination results showed that the cat had macrocytic hypochromic anemia accompanied by thrombocytopenia. Examination of the blood smear preparations found coccoid formations with short chains or rod formations in the cat's erythrocytes which indicated a positive result for Hemobartonella felis. Case animal was diagnosed with unilateral rhinitis and Hemobartonella felis infection. The therapy given consisted of Doxycycline antibiotics at a dose of 10 mg/kg once a day for 14 days, anti-inflammatory Dexamethasone at a dose of 0.5 mg once a day for 5 days and Sangobion as a supportive therapy 1 capsule once a day for 10 days. The therapy given helps to improve the condition of the case animal. General check up of health conditions is required during the maintenance period.

Simultaneous Presentation of Dexamethasone and Nerve Growth Factor via Layered Carbon Nanotubes and Polypyrrole to Interface Neural Cells.

The implantation of neural electrodes usually induces acute and chronic inflammation, which can result in the formation of glial scars encapsulating the implanted electrodes and the loss of neurons near the active electrode sites. Local presentation of anti-inflammatory drugs or neural protective factors has been evidenced as an effective strategy to modulate inflammatory responses and promote electrode-neuron integration. Here, a novel delivery system for the simultaneous presentation of both anti-inflammatory drugs (dexamethasone, Dex) and nerve-growth-promoting factors (nerve growth factor, NGF) from the electrode sites was developed via layer-structured carbon nanotubes and conductive polymers. The modified electrodes exhibited higher charge storage capacitance and lower electrochemical impedance compared to unmodified electrodes and electrodes coated with polypyrrole/Dex. Dex released from the functional coating under controlled electrochemical stimulation was able to inhibit the lipopolysaccharide-induced secretion or mRNA transcription of inflammatory cytokines, including nitric oxide, TNF-α, and IL-6 in RAW264.7 cells, and control the activation of cultured astrocytes. In addition, the functional coatings did not show a toxic effect on PC12 cells and primary neural cells but exhibited promoted activities on the adhesion, growth, and neurite extension of neural cells.

Green versatile micellar electrokinetic chromatographic method for determination of six antimicrobial and anti-inflammatory drugs in combined dosage forms

AbstractA fast reliable micellar electrokinetic methodology was investigated for the concurrent quantitation of six antimicrobial and anti-inflammatory drugs, namely, ciprofloxacin, dexamethasone, metronidazole, ornidazole, spiramycin and tinidazole. The method has the merits of rapidity, precision, and sensitivity. The separation was carried out in less than 7 min by applying a basic background electrolyte consisting of 25 mM disodium tetraborate buffer, pH 9 containing 50 mM SDS at 25 kV using photodiode array detector at 230 and 315 nm. The internal standard used during analysis was cromolyn sodium and validation was carried out following ICH guidelines. The proposed method showed linear response over the range from 0.5 to 10.0 μg mL−1 reaching limits of detection and limits of quantitation in the ranges of 0.09–0.2 μg mL−1 and 0. 27–0.6 respectively. The method's greenness was estimated using the GAPI tool where excellent greenness was concluded. Co-formulated or single-ingredient commercial preparations were investigated and the results were statistically evaluated.

Regulating macrophage-MSC interaction to optimize BMP-2-induced osteogenesis in the local microenvironment.

Bone morphogenetic protein (BMP-2) has been approved by the FDA to promote bone regeneration, but uncertain osteogenic effect and dose-dependent side effects may occur. Osteoimmunomodulation plays an important role in growth factor-based osteogenesis. Here, we explored how proinflammatory signals affect the dose-dependent osteogenic potential of BMP-2. We observed that the expression level of local IL-1β did not increase with the dose of BMP-2 in the mouse osteogenesis model. A low dose of BMP-2 could not promote new bone formation, but trigger the release of IL-1β from M1 macrophages. As the dose of BMP-2 increased, the IL-1β expression and M1 infiltration in local microenvironment were inhibited by IL-1Ra from MSCs under osteogenic differentiation induced by BMP-2, and new bone tissues formed, even excessively. Anti-inflammatory drugs (Dexamethasone, Dex) promoted osteogenesis via inhibiting M1 polarization and enhancing BMP-2-induced MSC osteo-differentiation. Thus, we suggest that the osteogenic effect of BMP-2 involves macrophage-MSC interaction that is dependent on BMP-2 dose and based on IL-1R1 ligands, including IL-1β and IL-1Ra. The dose of BMP-2 could be reduced by introducing immunoregulatory strategies.

Toward discovering a novel family of peptides targeting neuroinflammatory states of brain microglia and astrocytes.

Microglia are immune-derived cells critical to the development and healthy function of the brain and spinal cord, yet are implicated in the active pathology of many neuropsychiatric disorders. A range of functional phenotypes associated with the healthy brain or disease states has been suggested from in vivo work and were modeled in vitro as surveying, reactive, and primed sub-types of primary rat microglia and mixed microglia/astrocytes. It was hypothesized that the biomolecular profile of these cells undergoes a phenotypical change as well, and these functional phenotypes were explored for potential novel peptide binders using a custom 7 amino acid-presenting M13 phage library (SX7) to identify unique peptides that bind differentially to these respective cell types. Surveying glia were untreated, reactive were induced with a lipopolysaccharide treatment, recovery was modeled with a potent anti-inflammatory treatment dexamethasone, and priming was determined by subsequently challenging the cells with interferon gamma. Microglial function was profiled by determining the secretion of cytokines and nitric oxide, and expression of inducible nitric oxide synthase. After incubation with the SX7 phage library, populations of SX7-positive microglia and/or astrocytes were collected using fluorescence-activated cell sorting, SX7 phage was amplified in Escherichia coli culture, and phage DNA was sequenced via next-generation sequencing. Binding validation was done with synthesized peptides via in-cell westerns. Fifty-eight unique peptides were discovered, and their potential functions were assessed using a basic local alignment search tool. Peptides potentially originated from proteins ranging in function from a variety of supportive glial roles, including synapse support and pruning, to inflammatory incitement including cytokine and interleukin activation, and potential regulation in neurodegenerative and neuropsychiatric disorders.

Pyelonephritis and Polycystic Kidneys in a Male Holstein Calf

Introduction: Pyelonephritis and cystitis in cattle are urinary tract bacterial infections that can ascend to the kidneys and cause inflammation. This study presented a rarely-seen clinical kidney complication in a male Holstein calf. This problem was accompanied by respiratory tract infections. Bacterial infection caused bovine pyelonephritis and cystitis and consequently, there was an inflammation in the kidneys. A wide range of bacteria were responsible for such infections. 
 Case report: A 5-day-old male Holstein calf was initially diagnosed with high body temperature (> 40˚C), followed by respiratory signs. Treatment with antibiotics and anti-inflammatory drugs (dexamethasone and gentamicin) began immediately after diagnosis of the high body temperature, but the clinical signs, such as appetite loss and cough did not fully disappear. The calf’s growth was hindered and finally, died at the age of 90 days. Post-mortem necropsy findings included inflamed and cystic kidneys that coexisted with severe lung infections.
 Conclusion: The present uncommon renal complication may provide further information about the physiology and pathology of such rare kidney disorders in newborn Holstein calves.

Novel Collagen Surgical Patches for Local Delivery of Multiple Drugs.

Effective control of post-operative inflammation after tissue repair remains a clinical challenge. A tissue repair patch that could appropriately integrate into the surrounding tissue and control inflammatory responses would improve tissue healing. A collagen-based hybrid tissue repair patch has been developed in this work for the local delivery of an anti-inflammatory drug. Dexamethasone (DEX) was encapsulated into PLGA microspheres and then co-electrocompacted into a collagen membrane. Using a simple process, multiple drugs can be loaded into and released from this hybrid composite material simultaneously, and the ratio between each drug is controllable. Anti-inflammatory DEX and the anti-epileptic phenytoin (PHT) were co-encapsulated and released to validate the dual drug delivery ability of this versatile composite material. Furthermore, the Young's modulus of this drug-loaded collagen patch was increased to 20 KPa using a biocompatible riboflavin (vitamin B2)-induced UV light cross-linking strategy. This versatile composite material has a wide range of potential applications which deserve exploration in further research.