Giardiasis and diarrhea in dogs: Does the microbiome matter?

BACKGROUND: Giardia duodenalis (Gd) causes intestinal parasitosis. The involvement of the intestinal microbiome in determining the infection's clinical phenotype is unknown. OBJECTIVE: Investigate the fecal microbiome features in dogs with giardiasis. ANIMALS AND METHODS: Cross-sectional study, including fecal samples of kenneled dogs with Gd diagnosed by fecal Giardia antigen dot ELISA. The fecal microbial compositional characteristics and dysbiosis index (DI) were compared between diarrheic and nondiarrheic dogs. RESULTS: Fecal samples of 38 Gd-infected dogs (diarrheic, 21; nondiarrheic, 17) were included. No differences were found in Faith's phylogenic diversity and beta diversity (weighted UniFrac distances) and in specific taxa abundances at the phylum, genus, and species levels, as well as in alpha and beta diversities between diarrheic and nondiarrheic dogs, and also when divided by sex or age. Among diarrheic dogs, alpha diversity was higher in males than in females (pairwise Kruskal-Wallis, q = 0.01). Among males, fecal abundances of the genus Clostridium (W = 19) and Clostridium spiroforme species (W = 33) were higher in diarrheic compared to nondiarrheic dogs. In diarrheic dog fecal samples, Proteobacteria were more prevalent (W = 1), whereas Verrucomicrobia were less prevalent in dogs <1 year of age than in older dogs. The fecal sample DI of 19 diarrheic and 19 nondiarrheic dogs was similar (median, -0.2; range, -4.3 to 4.5 and median, -1.0; range, -4.3 to 5.8, respectively). CONCLUSIONS: The fecal microbial composition of symptomatic and asymptomatic dogs with giardiasis is similar. Based on fecal DI, giardiasis is not characterized by prominent dysbiosis. Other host and parasite characteristics might determine the severity of giardiasis in dogs.

Therapeutic efficacy and pharmacokinetics of liposomal-cannabidiol injection: a pilot clinical study in dogs with naturally-occurring osteoarthritis.

Introduction: Osteoarthritis is a common disease in dogs resulting in chronic pain and decreased wellbeing. Common analgesics such as non-steroidal anti-inflammatories may fail to control pain and can produce major adverse effects. Study objectives were to evaluate pharmacokinetics, therapeutic efficacy, and safety of subcutaneous liposomal-cannabidiol (CBD) as an additional analgesic therapy in dogs suffering from naturally-occurring osteoarthritis. Methods: Six such dogs were recruited following ethics approval and owner consent. Dogs were administered a single subcutaneous injection of 5 mg/kg liposomal-CBD. Plasma concentrations of CBD, blood work, activity monitoring collar data, wellbeing questionnaire (owners) and pain scoring (veterinarian) were performed at baseline and monitored up to six weeks following intervention. Data overtime were compared with baseline using linear-regression mixed-effects. P-value was set at 0.05. Results: CBD plasma concentrations were observed for 6 weeks; median (range) peak plasma concentration (Cmax) was 45.2 (17.8-72.5) ng/mL, time to Cmax was 4 (2-14) days and half-life was 12.4 (7.7-42.6) days. Median (range) collar activity score was significantly increased on weeks 5-6; from 29 (17-34) to 34 (21-38). Scores of wellbeing and pain evaluations were significantly improved at 2-3 weeks; from 69 (52-78) to 53.5 (41-68), and from 7.5 (6-8) to 5.5 (5-7), respectively. The main adverse effect was minor local swelling for several days in 5/6 dogs. Conclusion: Liposomal-CBD administered subcutaneously produced detectable CBD plasma concentrations for 6 weeks with minimal side effects and demonstrated reduced pain and increased wellbeing as part of multimodal pain management in dogs suffering from osteoarthritis. Further placebo-controlled studies are of interest.

Zinc chloride is effective as an antibiotic in biofilm prevention following septoplasty.

Biofilm-state bacterial infections associated with inserted medical devices constitute a massive health and financial problem worldwide. Although bacteria exhibit significantly lower susceptibility to antibiotics in the biofilm state, the most common treatment approach still relies on antibiotics, exacerbating the phenomenon of antibiotic-resistant bacteria. In this study, we aimed to assess whether ZnCl2 coating of intranasal silicone splints (ISSs) can reduce the biofilm infections associated with the insertion of these devices and prevent the overuse of antibiotics while minimizing waste, pollution and costs. We tested the ability of ZnCl2 to prevent biofilm formation on ISS both in vitro and in vivo by using the microtiter dish biofilm formation assay, crystal violet staining, and electron and confocal microscopy. We found a significant decrease in biofilm formation between the treatment group and the growth control when ZnCl2-coated splints were placed in patients' nasal flora. According to these results, infections associated with ISS insertion may be prevented by using ZnCl2 coating, thereby obviating the overuse and abuse of antibiotics.

A Case Report of Subcutaneously Injected Liposomal Cannabidiol Formulation Used as a Compassion Therapy for Pain Management in a Dog.

A 14-year-old intact mixed breed dog (26 kg) was submitted for a novel cannabidiol (CBD) analgesic treatment. The dog was cachectic and had a testicular neoplasia, hip and elbow osteoarthritis and severe cervical pain. Analgesic treatment included canine osteoarthritic supplement, robencoxib and gabapentin. An additional liposomal CBD injectable formulation at 5 mg/kg was administered subcutaneously between the shoulder blades. The dog was monitored using an activity monitoring collar (PetPace), owner wellbeing questionnaire (Canine Brief Pain Inventory; CBPI), pain interactive visual analog scale (iVAS), blood work and CBD plasma concentrations. A week from the injection and up to 3 weeks afterwards the dog had improved CBPI and iVAS pain scores, and increased collar activity scores. CBD was quantified in plasma for 28 days. Due to disease progression, further difficulty to rise and walk, and relapse to pain after 3 weeks, the owners requested a second liposomal CBD injection, which was performed 4 weeks following the first injection using 3 mg/kg dose. Two days later, the dog was found dead in the yard under direct sun, while environmental temperature was 37°C. Major findings on necropsy revealed evidence of heat stroke and severe cervical disc protrusion with spinal hematoma, none related to liposomal CBD. In conclusion, subcutaneous liposomal CBD produced quantifiable CBD plasma concentrations for 28 days and may be an effective additional treatment as part of multimodal pain management in dogs.

Aspects in controlled drug delivery for topical applications in veterinary medicine.

The controlled release of drugs is an appealing area of research as it provides numerous benefits in veterinary and human medicine. In this paper we attempt to analyze certain aspects related to topical drug delivery systems, their successes and failures, and their place in veterinary medicine. Some emphasis is given to the pharmaceutical aspects of the delivery systems, where the material available made it possible. Purely topical devices, such as cattle ear tags and various collars, as well as some topically administered bioavailable delivery systems are discussed. Special attention is given to hitherto under-evaluated delivery systems, such as topical varnishes. A carefully selected bibliography aims to lead the reader easily to the facts, without providing overwhelming data of varying quality. We believe that the paper may be of interest to practicing veterinarians as well as to pharmaceutical scientists working or considering practice in the area.

Prognostic markers and assessment of a previously published clinical severity index in 109 hospitalised dogs with acute presentation of pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is common in dogs. Nevertheless, validated clinical severity index (CSI) scoring systems to assess severity and guide treatment in current, large-scale studies are unavailable. METHODS: This is a retrospective study including 109 dogs. Pancreatitis was diagnosed based on clinical signs, abdominal sonographic evidence, positive pancreatic lipase assays and experts' assessment consensus. RESULTS: The survival rate was 75 per cent (82 dogs). Azotaemia and presence of local complications (ie, ascites) and secondary complications (ie, acute kidney injury and acute respiratory distress syndrome) were significantly associated with death. In agreement with the previously published CSI, respiratory anomalies were significantly associated with death. However, in disagreement with that study, high scores in the kidney and local abdominal complication categories and the sum of scores of all nine categories, but not high gastrointestinal category score, were also significantly associated with death. A final CSI score of at least 4 was associated with death. CONCLUSIONS: This study has validated a nine-category CSI, proven a useful assessment tool in dogs with AP. Several previously reported and novel prognostic markers were assessed.

A retrospective study of 157 hospitalized cats with pancreatitis in a tertiary care center: Clinical, imaging and laboratory findings, potential prognostic markers and outcome.

BACKGROUND: Pancreatitis in cats (FP) has been increasingly diagnosed in recent years, but clinical studies of large numbers of affected cats are scarce. OBJECTIVES: To describe a large cohort of cats with FP requiring hospitalization. ANIMALS: One hundred and fifty-seven client-owned cats. METHODS: Retrospective study, including cats diagnosed with pancreatitis based on sonographic evidence, positive SNAP feline pancreatic lipase immunoreactivity test results, increased 1,2-o-dilauryl-rac-glycerol-glutaric Acid-(6'-methylresorufin ester)-lipase activity, histopathology, or some combination of these. RESULTS: One-hundred and twenty-two cats (77.7%) survived to discharge. Median time from onset of clinical signs to presentation was longer (P = .003) in nonsurvivors. Causes of FP included recent general anesthesia, trauma, hemodynamic compromise, and organophosphate intoxication, but most cases (86.6%) were idiopathic. Ultrasonographic findings consistent with pancreatitis were documented in 134 cats, including pancreatomegaly (81.3%), decreased (31.3%), or increased (14.9%) pancreatic echogenicity, extra-hepatic biliary tract dilatation (24%), and increased peri-pancreatic echogenicity (13%). Lethargy (P = .003), pleural effusion (P = .003), hypoglycemia (P = .007), ionized hypocalcemia (P = .016), azotemia (P = .014), parenteral nutrition administration (P = .013), and persistent anorexia during hospitalization (P = .001) were more frequent in nonsurvivors, whereas antibiotics were more frequently administered to survivors (P = .023). Nevertheless, when Bonferroni's correction for multiple comparisons was applied, none of the variables was statistically significant. CONCLUSIONS AND CLINICAL IMPORTANCE: Previously unreported, clinically relevant, potential prognostic factors, including hypoglycemia, azotemia, parenteral nutrition, and withholding antibacterial treatment were identified in this exploratory study. These preliminary results should be examined further in confirmatory studies.

Evaluation of a spot-on imidacloprid-moxidectin formulation (Advocate®) for the treatment of naturally occurring esophageal spirocercosis in dogs: a double-blinded, placebo-controlled study.

BACKGROUND: Dogs are the definitive hosts of Spirocerca lupi. Spirocercosis is treated by prolonged avermectin administration by injection or daily oral doses. In this prospective, double-blinded, placebo-controlled, clinical trial, the efficacy of imidacloprid and moxidectin spot-on formulation (Advocate®) was compared to injectable doramectin (Dectomax®). Dogs diagnosed with benign esophageal spirocercosis were divided randomly into doramectin (400 µg/kg IM) or moxidectin and imidacloprid spot-on (2.5-6.25 mg/kg and 10-25 mg/kg, respectively) groups and treated weekly for 12 consecutive weeks. Dogs were followed for 20 weeks by physical examination, owners' questionnaire, blood work, fecal floatation, PCR and endoscopy. RESULTS: All the doramectin group dogs (n = 10) completed the treatment and follow-up, and the disease had completely resolved in all by week 12. Of the Advocate® group (n = 10), four had complete resolution at week 12, four had partial resolution, one dog did not respond to treatment, and one dog was switched to the doramectin protocol on week 5 due to persistent severe clinical signs. PCR analysis was more sensitive in detecting S. lupi eggs compared to fecal floatation. Discrepancies were detected on 22 occasions, of which on 20 occasions, the PCR was positive while fecal floatation was negative, and only on two occasions the PCR results were negative while fecal flotation was positive. CONCLUSIONS: The present results indicate that weekly Advocate® spot-on administration may be effective for treating benign esophageal spirocercosis, but is less effective than the currently used injectable doramectin therapy at the dose and duration used herein.

RETROSPECTIVE EVALUATION OF A NOVEL SUSTAINED-RELEASE IVERMECTIN VARNISH FOR TREATMENT OF WOUND MYIASIS IN ZOO-HOUSED ANIMALS.

Myiasis is a major disease condition in human and veterinary medicine. Domestic, free-ranging, and zoo-housed animals can be severely affected by myiasis. Depending on case severity, multiple treatment episodes may be indicated and can lead to recurrent capturing, handling stress, and anesthetics, all of which increase the risk of adverse responses (including death) individually and also in the herd. As an insecticide, ivermectin is often used for larval control. A total of 28 individual myiasis cases were retrospectively evaluated, out of which 11 cases were also treated using an ivermectin sustained-release varnish (SRV). The clinical outcome of all cases was assessed and the results suggest that the use of a topical ivermectin SRV (with or without concurrent injectable ivermectin) can reduce handling and treatments, has no adverse effects, and has minimal recurrence of the disease when compared with cases treated without it.

Chlorhexidine sustained-release varnishes for catheter coating - Dissolution kinetics and antibiofilm properties.

Catheter-associated urinary tract infections are difficult to eradicate or prevent, due to their biofilm-related nature. Chlorhexidine, a widely used antiseptic, was previously found to be effective against catheter-related biofilms. For the present study, we developed sustained-release chlorhexidine varnishes for catheter coating and evaluated their antibiofilm properties and chlorhexidine-dissolution kinetics under various conditions. The varnishes were based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit® RL). Chlorhexidine was released by diffusion from a heterogeneous matrix in the case of the ethylcellulose-based formulation, and from a homogeneous matrix in the case of Eudragit® RL. This dictated the release pattern of chlorhexidine under testing conditions: from film specimens, and from coated catheters in a static or flow-through system. Momentary saturation was observed with the flow-through system in Eudragit® RL-based coatings, an effect that might be present in vivo with other formulations as well. The coatings were retained on the catheters for at least 2weeks, and showed prolonged activity in a biological medium, including an antibiofilm effect against Pseudomonas aeruginosa. The current study demonstrates the potential of catheter coatings with sustained release of chlorhexidine in the prevention of catheter-associated urinary tract infections.

A Sustained-Release Membrane of Thiazolidinedione-8: Effect on Formation of a Candida/Bacteria Mixed Biofilm on Hydroxyapatite in a Continuous Flow Model.

Thiazolidinediones (TZDs) have been found to act as effective quorum sensing quenchers, capable of preventing biofilm formation. Our previous studies demonstrated a profound antibiofilm effect of the TZD derivative thiazolidinedione-8 (S-8), either in solution or incorporated into a sustained-release membrane (SRM-S-8) under batch conditions. In the present study, we used a constant depth film fermenter model in order to investigate the impact of SRM-S-8 on mixed C. albicans-S. mutans biofilm development, under flow conditions. We found that essential parameters of cospecies biofilm maintenance and maturation, such as metabolic activity, biofilm thickness, roughness, extracellular polysaccharides production, and morphology of both pathogens, were altered by SRM-S-8 in the flow system. We propose that prolonged and sustained release of S-8 in a flow-through system allows better penetration of the active agent to deeper layers of the mixed biofilm, thereby increasing its activity against both pathogens. In conclusion, the use of a locally applied sustained-release drug delivery system of S-8 can affect the dental polymicrobial biofilm, resulting in clinical improvements and a better patient compliance.

Borrelia persica infection in dogs and cats: clinical manifestations, clinicopathological findings and genetic characterization.

BACKGROUND: Relapsing fever (RF) is an acute infectious disease caused by arthropod-borne spirochetes of the genus Borrelia. The disease is characterized by recurrent episodes of fever that concur with spirochetemia. The RF borrelioses include louse-borne RF caused by Borrelia recurrentis and tick-borne endemic RF transmitted by argasid soft ticks and caused by several Borrelia spp. such as B. crocidurae, B. coriaceae, B. duttoni, B. hermsii, B. hispanica and B. persica. Human infection with B. persica is transmitted by the soft tick Ornithodoros tholozani and has been reported from Iran, Israel, Egypt, India, and Central Asia. METHODS: During 2003-2015, five cats and five dogs from northern, central and southern Israel were presented for veterinary care and detected with borrelia spirochetemia by blood smear microscopy. The causative infective agent in these animals was identified and characterized by PCR from blood and sequencing of parts of the flagellin (flab), 16S rRNA and glycerophosphodiester phosphodiestrase (GlpQ) genes. RESULTS: All animals were infected with B. persica genetically identical to the causative agent of human RF. Phylogenetic analysis indicated that DNA sequences from these pet carnivores clustered together with B. persica genotypes I and II from humans and O. tholozani ticks and distinctly from other RF Borrelia spp. The main clinical findings in cats included lethargy, anorexia, anemia in 5/5 cats and thrombocytopenia in 4/5. All dogs were lethargic and anorectic, 4/5 were febrile and anemic and 3/5 were thrombocytopenic. Three dogs were co-infected with Babesia spp. The animals were all treated with antibiotics and the survival rate of both dogs and cats was 80 %. The cat and dog that succumbed to disease died one day after the initiation of antibiotic treatment, while survival in the others was followed by the rapid disappearance of spirochetemia. CONCLUSIONS: This is the first report of disease due to B. persica infection in cats and the first case series in dogs. Infection was associated with anemia and thrombocytopenia. Fever was more frequently observed in dogs than cats. Domestic canines and felines suffer from clinical disease due to B. persica infection and may also serve as sentinels for human infection.

Serological cross-reactivity of three commercial in-house immunoassays for detection of Dirofilaria immitis antigens with Spirocerca lupi in dogs with benign esophageal spirocercosis.

The nematode Spirocerca lupi infects dogs and is endemic in Israel. It leads to formation of esophageal nodules and neoplasia. Infection is diagnosed by coproscopy, endoscopy and radiography. Dirofilaria immitis causes heartworm disease in dogs, and has a world-wide distribution, but autochthonous infection has never been detected in Israel. Infection is confirmed based on identifying D. immitis microfilariae, in concentrated blood specimens by microscopy (Knott's test or other tests) and serological tests specifically detecting circulating adult worm antigens. In the first part of this study, sera from dogs definitively diagnosed with esophageal spirocercosis by endoscopy were examined using three in-house immunoassays for detecting D. immitis antigen, and were positive in 2/19 (10.5%), 5/35 (14.3%) and 14/48 (29.2%) dogs, in assays 1 to 3, respectively, with no statistical difference between assays (P=0.08). Next, sera from 32 additional dogs with confirmed esophageal spirocercosis, which were confirmed to be negative for D. immitis and Dirofilaria repens DNA using a sensitive high-resolution melt PCR were tested using assay 3 and 8/32 (25%) were positive. These results demonstrate serological cross-reactivity between D. immitis and S. lupi in blood samples of dogs. In areas where the distributions of both nematodes overlap, this cross-reactivity should be considered when dog are screened for heartworm disease.

Spirocercosis in dogs in Israel: A retrospective case-control study (2004-2009).

This case-control retrospective study (years 2004-2009) investigated the epidemiological, clinical, and diagnostic test findings of dogs with esophageal spirocercosis (ES) presented to the Hebrew University Veterinary Teaching Hospital (HUVTH) and coproscopy-positive dogs at the Kimron Veterinary Institute (KVI), Israel. It included 133 dogs with ES and 133 negative controls diagnosed at the hospital, and 343 dogs diagnosed at the KVI. The average incidence of ES at the HUVTH was 22.5/year, and the percentage of spirocercosis cases was stable at both institutions (HUVTH, 0.67-1.23%; KVI, 5-8%). Dogs aged > 5 years old had 100-fold likelihood to be infected compared to dogs aged ≤ 1 year of age (P < 0.001). Mean body weight (P = 0.0004), proportion of Retrievers (P = 0.002) and sporting breed dogs (P = 0.006) were higher, while proportion of toy breeds (P = 0.004) was lower in the ES group compared to the control group. The proportion of cases from Greater Tel-Aviv decreased (P = 0.002), while that of those from Judea and Jerusalem increased (P = 0.01) compared to the 1990 s. Spirocercosis occurred in 22 dogs despite past prophylactic avermectin treatment. Vomiting and regurgitation were the most common clinical signs of ES. Coproscopy was S. lupi-positive in 33/60 dogs (55.0%). The median number of esophageal nodules was two (range 1-8), with a median diameter of 3.5 cm (range 1.0-11.0). Malignant esophageal lesion transformation was confirmed in 29 dogs (22%). Despite preventive attempts, spirocercosis has spread in Israel over time, compared to previous findings, raising questions about the efficacy of the currently accepted prophylactic protocol is incompletely effective.

Local sustained-release delivery systems of the antibiofilm agent thiazolidinedione-8 for prevention of catheter-associated urinary tract infections.

Thiazolidinedione-8 (TZD-8) is an anti-quorum-sensing molecule that has the potential to effectively prevent catheter-associated urinary tract infections, a major healthcare challenge. Sustained-release drug-delivery systems can enhance drugs' therapeutic potential, by maintaining their therapeutic level and reducing their side effects. Varnishes for sustained release of TZD-8 based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit(®) RL) were developed. The main factors affecting release rate were found to be film thickness and presence of a hydrophilic or swellable polymer in the matrix. The release mechanism of ethylcellulose-based systems matched the Higuchi model. Selected varnishes were retained on catheters for at least 8 days. Sustained-release delivery systems of TZD-8 were active against Candida albicans biofilms. The present study demonstrates promising results en route to developing applications for the prevention of catheter-associated infections.

Changes in blood pressure following escalating doses of phenylpropanolamine and a suggested protocol for monitoring.

This prospective, cross-over, blinded study evaluated the effect of various doses of phenylpropanolamine (PPA) on blood pressure in dogs. Dogs were randomized to receive a placebo or 1 of 3 dosages of immediate release PPA, q12h for 7 days [1 mg/kg body weight (BW), 2 mg/kg BW, or 4 mg/kg BW] in a cross-over design. Blood pressure was recorded every 2 h, for 12 h, on days 1 and 7. There were significant increases in systolic, diastolic, and mean blood pressure following administration of PPA at 2 mg/kg BW and 4 mg/kg BW. A significant decrease in heart rate was also noted at all PPA dosages, but not in the placebo. Administration of PPA was associated with a dose response increase in blood pressure. Dosages of up to 2 mg/kg BW should be considered safe in healthy dogs.

Changements de la pression artérielle après des doses progressives de phénylpropanolamine et suggestion d'un protocole de surveillance. Cette étude prospective à l'insu et à plan d'étude croisée a évalué l'effet de diverses doses de phénylpropanolamine (PPA) sur la pression artérielle des chiens. Les chiens ont reçu au hasard un placebo ou 1 de 3 doses de PPA à action immédiate, q12h pendant 7 jours (1 mg/kg de poids corporel [PC], 2 mg/kg PC ou 4 mg/kg PC) dans un plan d'étude croisé. La pression artérielle a été consignée toutes les 2 h, pendant 12 h, aux jours 1 et 7. Il n'y a pas eu de hausses significatives de la pression artérielle systolique et diastolique ni de la pression artérielle moyenne après l'administration de PPA à 2 mg/kg PC et à 4 mg/kg PC. Une baisse significative de la fréquence cardiaque a aussi été notée dans toutes les doses de PPA, mais non avec le placebo. L'administration de PPA a été associée à une hausse de la pression artérielle en fonction de la dose. Des doses jusqu'à 2 mg/kg PC devraient être considérées sûres chez des chiens en santé.(Traduit par Isabelle Vallières).

Serum acute phase protein concentrations in dogs with spirocercosis and their association with esophageal neoplasia - a prospective cohort study.

Spirocerca lupi, the dog esophageal worm, typically induces formation of esophageal nodules, which may transform to sarcoma. Ante mortem discrimination between benign and malignant esophageal masses is challenging. Serum acute phase proteins (APPs) are utilized in diagnosis and prognosis of various canine diseases as markers of inflammation. This study characterized serum APPs concentrations in dogs with benign and malignant esophageal spirocercosis and evaluated their accuracy in differentiating benign from malignant lesions. Seventy-eight client-owned dogs with esophageal spirocercosis were included. Serum C-reactive protein (CRP), haptoglobin, serum-amyloid A (SAA) and albumin concentrations were measured upon diagnosis and follow-up visits, and compared with healthy dogs, and between malignant and benign cases. Haptoglobin, CRP and SAA concentrations were higher, and albumin concentration was lower (P<0.001 for all) in infected dogs compared to healthy controls. Dogs with suspected neoplasia had significantly higher CRP (P=0.011), haptoglobin (P=0.008) and SAA (P=0.05), and lower albumin (P=0.012) concentrations compared to dogs with benign esophageal nodules. APPs moderately discriminated between suspected malignant and benign esophageal disease. None of the dogs with suspected neoplasia had concurrent normal concentrations of all APPs. The present results indicate that canine spirocercosis is characterized by an acute phase reaction, both at presentation and during treatment. When concentrations of all four APPs are within reference range, esophageal malignancy is highly unlikely. Although concentrations of all positive APPs were significantly higher in suspected neoplastic cases compared to benign ones, moderate discriminatory power limits their clinical use. Neither APP was useful to monitor response to treatment.

Azithromycin pharmacokinetics in the serum and its distribution to the skin in healthy dogs and dogs with pyoderma.

Serum and skin tissue azithromycin (AZM) concentrations were analysed in healthy and pyoderma affected dogs to determine AZM pharmacokinetics and to establish the effect of disease on AZM skin disposition. AZM was administered orally to two groups of healthy dogs: (1) at 7.02 mg/kg (n=7) and (2) at 11.2mg/kg (n=9). A crossover design was used on five of them. Seven dogs with pyoderma were treated with AZM at 10.7 mg/kg. The two groups of healthy dogs received AZM once daily over three consecutive days and dogs with pyoderma received the same treatment repeated twice with an interval of 1 week. AZM concentrations were determined by liquid chromatography-tandem mass spectrometry. AZM was rapidly absorbed and slowly excreted. In healthy dogs, maximum serum concentrations appeared 2h after administration and were (mean ± standard deviation) 0.60 ± 0.25 µg/mL and 1.03 ± 0.43 µg/mL, and the half-lives were 49.9 ± 5.10 and 51.9 ± 6.69 h for doses of 7.02 and 11.2mg/kg, respectively. Clearance (CL0-24/F) was similar in both dosing groups (1.24 ± 0.24 and 1.29 ± 0.24 L/h/kg) and the respective mean residence time (MRT0-24) was 11.1 ± 0.8 and 8.4 ± 2.2h. The skin concentration in healthy dogs was 3.5-6.5 and 5.0-12.0 times higher than the corresponding serum concentration after the two doses and increased after the cessation of AZM administration. The ratio increased significantly in inflamed tissue (9.5-26.2).

Development and in vitro characterization of floating sustained-release drug delivery systems of polyphenols.

The aim of this study was to develop and characterize floating stomach-retentive matrix tablets that will deliver polyphenols in a controlled release manner. The tablets were prepared by direct compression. A number of polymers were examined and egg albumin was chosen in light of a better performance in terms of floating behavior and decomposition time. Dissolution studies for three representative polyphenols loaded into a number of formulations were performed using the "f2" factor in order to compare release profiles of different polyphenols and formulations. The release data showed a good fit into the power law equation and zero-order kinetics has been determined for some of the systems. Erosion and textural analysis studies revealed that higher concentration of egg albumin results in a higher gel strength that is less susceptible to erosion, potentially leading to a prolonged delivery time of drug. The ability of egg albumin-based tablets to resist high mechanical forces was also determined, while comparison to cellulose-derived polymers revealed that the latter have a much lower ability to resist the same forces. The developed delivery system has the potential to increase the efficacy of the therapy for various pathological stomach conditions and to improve patient compliance.

Prevention of initial biofilm formation on ureteral stents using a sustained releasing varnish containing chlorhexidine: in vitro study.

BACKGROUND AND PURPOSE: Ureteral stents are being used exceedingly in the field of urology, and with advancements in endourology, this trend is increasing. Bacterial colonization and proliferation on the stent surface may result in urinary tract infections (UTIs) necessitating the administration of antibiotics that, in turn, may lead to the development of antibiotic-resistant bacterial strains. Several studies have shown that sustained release varnish (SRV) combined with antibiotics or antiseptics can prevent the proliferation of bacteria on urethral catheters. This is the first study that evaluates this technique implemented on ureteral stents. MATERIALS AND METHODS: We evaluated growth inhibition on ureteral stent segments coated with chlorhexidine (CHX) 1% SRV. The tests were conducted using common urinary pathogens: Enterococci, Pseudomonas, and Escherichia coli. Coated stent segments were inserted into bacterial suspensions. Controls included uncoated stent segments and stents coated with placebo SRV (without CHX). RESULTS: Bacterial growth measured as turbidity and as colony-forming units showed a significant inhibition effect of initial bacteria adhesion to the CHX-SRV coated stent segments compared with the controls (P<0.001). This inhibitory effect was apparent in each of the bacteria tested and was confirmed by inspection of the stent segments under an electron microscope. In a kinetic experiment using CHX 2% SRV, we were able to prolong the growth inhibition effect from 1 week to nearly 2 weeks. CONCLUSIONS: We believe this technique may play a significant role in reducing ureteral stent-associated UTIs. Further studies are needed before this approach can be implemented in clinical practice.