Placebo-treated Controls Research Articles

Pre-Clinical Study of Hydro-Ethanol (60:40) Extract of <i>Areca catechu</i> (L.) on Testicular Androgenesis in Albino Rat: An Approach for Herbal Male Contraceptive Development

The present study was designed to determine the anti-testicular activity of hydro-ethanol seed extract of Areca catechu (10, 20 and 40 mg) in dose-dependent fashion in albino rats. Seminal vesicular fructose (SVF), oxidative stress sensors, gene expression, somatic weight, reproductive organo-somatic indices, spermiological, hormonal profile, and testicular histological examination for qualitative and quantitative investigations of spermatogenesis were observed. In compared to the placebo treated control (PTC), the exposure of the said doses showed a statistical significant downward deviation in the spermiological, hormonal, SVF profile, kinetics of testicular key androgenic dehydrogenase enzymes, and diameters of seminiferous tubules. Anti-oxidant enzyme kinetics were reduced significantly against PTC, and the quantity of malondialdehyde in male gonad and sperm precipitate was elevated in significant level (p<0.05). Expression of apoptotic promoting gene in testis was increased (p<0.05) and anti-apoptotic Bcl-2 gene expression exhibited a significant decrease (p<0.05) in treated group comparison to the PTC. The alterations in the activities of phosphatases in hepatic tissue was not significant from the background of PTC suggesting that the plant has no systematic undesirable effect in physiological processes. The observation highlighted that 10 mg dose as the threshold dose for imposition of such anti- testicular activity leading to male contraception.

Advancements in Ichthyosis Treatment in Pediatric Patients: Evaluating the Impact of Immune System Inhibitors Targeting TNF-alpha, IL-17A, IL-4, and IL-12

Lamellar, X-linked recessive, and Vulgaris ichthyosis represent rare genetic variants distinguished by abundant dry surface scales. The etiology of childhood ichthyosis involves a combination of acquired and inherited factors. Children with Ichthyosis have a Th17-dominant immune profile, similar to psoriasis, with a correlation between ichthyosis severity, erythema, Trans Epidermal Water Loss (TEWL), and immunological markers. In order to examine the safety and effectiveness of immune system inhibitors that target TNF-alpha, IL-17A, IL-4, and IL-12 in the treatment of pediatric Ichthyosis, a retrospective research study was conducted on 30 pediatric patients aged 6-12 years at tertiary care pediatric dermatology hospitals in UAE, for a time duration of 5 months. IL-17-A is a key cytokine of Ichthyosis, and its specific suppression is considered necessary in contrast to other cytokines. Consequently, the choice of treatment was dictated by elements unique to the condition and the intensity of symptoms, focusing on using Secukinumab as an IL-17-A inhibitor. The findings showed that, following five months of treatment, patients receiving secukinumab showed positive outcomes, with their ichthyosis area severity index score declining by 45 to 50%. Additionally, the proinflammatory rate of cytokines was significantly lower in this group of patients compared to the placebo-treated control group. The safety and Efficacy of Secukinumab compared to Ixekizumab and Brodalumab vs placebo were examined using t-tests, with statistical significance determined at P< 0.05. The present research study concludes that Secukinumab effectively enhances skin texture and reduces scaling severity in Ichthyosis, suggesting clinical relevance. The findings underscore Secukinumab’s potential as a beneficial agent for various ichthyosis types, such as lamellar, X-linked, and vulgaris. The study’s comparison with placebo and other IL-17A inhibitors like Ixekizumab and Brodalumab provides valuable insights into Secukinumab’s Efficacy and potential clinical uses.

Low-Level Laser Therapy for the Treatment of Oral Mucositis Induced by Hematopoietic Stem Cell Transplantation: A Systematic Review with Meta-Analysis.

Oral mucositis is a common and debilitating side effect induced by stem cell transplantation that is experienced by cancer patients undergoing chemotherapy or radiation therapy. This condition involves inflammation and ulceration of the oral mucosa, leading to pain, difficulty with eating and speaking, and an increased risk of infections. Mucositis not only compromises the quality of life for cancer patients, but also affects treatment outcomes and may necessitate dose reductions or treatment delays. This scientific article provides a comprehensive overview of mucositis. The purpose of this literature review with a meta-analysis is to evaluate the efficacy of laser therapy in treating post-transplant mucositis. Materials and methods: A search of the literature from 3 May 2023 was carried out on three online databases, PubMed, Scopus, and Web of Science. Only studies that treated patients with laser therapy were considered; only studies with the placebo-treated control group were considered. Review Manager version 5.2.8 (Cochrane Collaboration) was used for the pooled analysis. We measured the std. mean difference between the two groups (laser and placebo). Results: There were 230 papers included in this review. Two hundred twenty-seven were excluded. Furthermore, a manual search was performed. After the search phase, three articles were considered in the study. The overall effect showed differences in the degree of mucositis in the laser-treated patients compared with the placebo group. The meta-analysis shows a reduction in the degree of mucositis in the patients treated with laser therapy (std. mean difference -1.34 [-1.98; -0.98]; C.I. 95%). Conclusions: The application of laser therapy results in decreased severity of oral mucositis from radiation and chemotherapy. Our study shows that the application of low-level laser therapy in the treatment of transplant mucositis has excellent efficacy in relieving the symptoms and severity of mucositis.

Acute Effects of Systemic Glucocorticoids on the Vocal Folds in a Pre-Clinical Model.

Systemic glucocorticoids (GC)s are employed to treat various voice disorders. However, GCs have varying pharmacodynamic properties with adverse effects ranging from changes in epithelial integrity, skeletal muscle catabolism, and altered body weight. We sought to characterize the acute temporal effects of systemic dexamethasone and methylprednisolone on vocal fold (VF) epithelial glucocorticoid receptor (GR) nuclear translocation, epithelial tight junction (ZO-1) expression, thyroarytenoid (TA) muscle fiber morphology, and body weight using an established pre-clinical model. We hypothesized dexamethasone and methylprednisolone will elicit changes in VF epithelial GR nuclear translocation, epithelial ZO-1 expression, TA muscle morphology, and body weight compared to placebo-treated controls. Forty-five New Zealand white rabbits received intramuscular injections of methylprednisolone (4.5 mg; n = 15), dexamethasone (450 µg; n = 15), or volume matched saline (n = 15) into the iliocostalis/longissimus muscle for 6 consecutive days. Vocal folds from 5 rabbits from each treatment group were harvested at 1-, 3-, or 7 days following the final injection and subjected to immunohistochemistry for ZO-1 and GR as well as TA muscle fiber cross-sectional area (CSA) measures. Dexamethasone increased epithelial GR nuclear translocation and ZO-1 expression 1-day following injections compared to methylprednisolone (P = .024; P = .012). Dexamethasone and methylprednisolone increased TA CSA 1-day following injections (P = .011). Methylprednisolone decreased body weight 7 days following injections compared to controls (P = .004). Systemic dexamethasone may more efficiently activate GR in the VF epithelium with a lower risk of body weight loss, suggesting a role for more refined approaches to GC selection for laryngeal pathology.

Relaxin elicits renoprotective actions accompanied by increasing bile acid levels in streptozotocin-induced diabetic mice

BackgroundThe peptide hormone relaxin has potent anti-fibrotic and anti-inflammatory properties in various organs, including the kidneys. However, the protective effects of relaxin in the context of diabetic kidney complications remain controversial. Here, we aimed to evaluate the effects of relaxin treatment on key markers of kidney fibrosis, oxidative stress, and inflammation and their subsequent impact on bile acid metabolism in the streptozotocin-induced diabetes mouse model. Methods and resultsMale mice were randomly allocated to placebo-treated control, placebo-treated diabetes or relaxin-treated diabetes groups (0.5 mg/kg/d, final 2 weeks of diabetes). After 12 weeks of diabetes or sham, the kidney cortex was harvested for metabolomic and gene expression analyses. Diabetic mice exhibited significant hyperglycaemia and increased circulating levels of creatine, hypoxanthine and trimethylamine N-oxide in the plasma. This was accompanied by increased expression of key markers of oxidative stress (Txnip), inflammation (Ccl2 and Il6) and fibrosis (Col1a1, Mmp2 and Fn1) in the diabetic kidney cortex. Relaxin treatment for the final 2 weeks of diabetes significantly reduced these key markers of renal fibrosis, inflammation, and oxidative stress in diabetic mice. Furthermore, relaxin treatment significantly increased the levels of bile acid metabolites, deoxycholic acid and sodium glycodeoxycholic acid, which may in part contribute to the renoprotective action of relaxin in diabetes. ConclusionIn summary, this study shows the therapeutic potential of relaxin and that it may be used as an adjunctive treatment for diabetic kidney complications.

Effects of adult Ascaris suum and their antigens (total and trans-cuticular excretory-secretory antigen, cuticular somatic antigen) on intestinal nutrient transport in vivo.

AbstractAscaris suumconstitutes a major problem in commercial pig farming worldwide. Lower weight gains in infected pigs probably result from impaired nutrient absorption. This study investigated intestinal nutrient transport in 4 groups of 6 pigs each, which were inoculated with 30 living adultA. suum, or antigen fractions consisting of (1) total excretory–secretory (ES) antigens of adult worms, (2) ES antigens secreted exclusively from the parasites' body surface (trans-cuticular ES) and (3) cuticular somatic antigens ofA. suum, compared to placebo-treated controls. Three days after inoculation into the gastrointestinal tract, glucose, alanine and glycyl-l-glutamine transport was measured in the duodenum, jejunum and ileum using Ussing chambers. Transcription of relevant genes [sodium glucose cotransporter 1 (SGLT1), glucose transporter 1 (GLUT1), GLUT2, hypoxia-inducible factor 1-alpha (Hif1α), interleukin-4 (IL-4), IL-13, signal transducer and activator of transcription 6 (STAT6), peptide transporter 1 (PepT1)] and expression of transport proteins [SGLT1, phosphorylated SGLT1, GLUT2, Na+/K+-ATPase, amino acid transporter A (ASCT1), PepT1] were studied. Although no significant functional changes were noted after exposure to adultA. suum, a significant downregulation of jejunal GLUT1, STAT6, Hif1αand PepT1 transcription as well as ileal GLUT2 and PepT1 expression indicates a negative impact of infection on transport physiology. Therefore, the exposure period of 3 days may have been insufficient for functional alterations to become apparent. In contrast,A. suumantigens mainly induced an upregulation of transport processes and an increase in transcription of relevant genes in the duodenum and jejunum, possibly as a compensatory reaction after a transient downregulation. In the ileum, a consistent pattern of downregulation was observed in all inoculated groups, in line with the hypothesis of impaired nutrient transport.

Antagonism of N/OFQ attenuates externalization of β1-adrenergic receptor and ventricular arrhythmias in acute myocardial ischemia rat model

Nociceptin/orphanin FQ (N/OFQ) and adrenergic activations play roles in promoting cardiac arrhythmia in acute myocardial ischemia but whether N/OFQ and β1-adrenergic activities interact and how they interact in the arrhythmogenesis are still unknown. We designed this study to investigate the potential interaction of N/OFQ and β1-adrenergic activities and the underlying mechanism in arrhythmogenesis in acute myocardial ischemia. Ventricular arrhythmia was evaluated in anaesthetized rats following permanent coronary artery occlusion (CAO), in presence and absence of UFP-101 (a selective antagonist of N/OFQ receptor). The changes of β1-adrenergic receptor (β1-AR) in plasma membrane of cardiomyocytes were quantitatively evaluated and the relations with the alterations of phosphorylated Raf kinase inhibitor protein (p-RKIP) and phosphorylated connexin 43 (p-Cx43) were investigated. The ventricular arrhythmia was 59% less in the animals pre-treated with UFP-101 than the placebo-treated control (difference of means = −2.41; 95% confidence interval (CI) −2.84 to −1.99; P < 0.001). Meanwhile, p-RKIP and membrane β1-AR in the myocardium were downregulated by 59% and 24%, respectively (p-RKIP: difference of means = −6.91; 95% CI -8.38 to −5.45; P < 0.001; membrane β1-AR difference of means = −27.06; 95% CI -29.89 to −24.23; P < 0.001). Artificial upregulation of RKIP by didymin significant increased β1-AR in plasma membrane of the cardiomyocytes in the animals prone to ventricular arrhythmia. The findings may suggest that activation of N/OFQ receptor in acute myocardial ischemia induces upregulation of p-RKIP, externalization of β1-adrenergic receptor and downregulation of p-Cx43 in the cardiomyocytes, which promotes ventricular arrhythmia.

The Maximum-Tolerated Dose and Pharmacokinetics of a Novel Chemically Modified Curcumin in Rats.

PurposeCMC 2.24, a chemically modified curcumin, was developed as a novel, pleiotropic MMP-inhibitor to treat various inflammatory/collagenolytic diseases including periodontitis. To date, this compound has shown efficacy in vitro, in cell culture, and in vivo (oral administration) in mice, rats and dogs. In preparation for possible Phase I human clinical trials, the current study describes the maximum-tolerated-dose (MTD), pharmacokinetics (PK), and toxicology of CMC 2.24 in the rat model.MethodsFor the MTD study, 30 Sprague-Dawley rats were randomly distributed into 5 groups (3M/3F per group): Placebo (vehicle; carboxymethylcellulose) and CMC 2.24 at various doses (50, 100, 500, 1000 mg/kg/day), were administered once daily by oral gavage for 5 days. For the PK study, 24 rats were administered either Placebo or CMC 2.24 (100mg/kg/day) once daily for 28 days or only once (500 or 1000 mg/kg). Analysis of this test compound was done using LC/MS/MS for PK evaluation on blood samples drawn from rats at multiple time points. The animals were sacrificed after 5 or 28 days of treatment, and blood chemistry and serology were analyzed. Major organs (heart, lung, liver, kidney, spleen, intestine, brain) were histologically examined at necropsy.ResultsOrally administered, CMC 2.24 did not produce significant changes in body weight, food consumption or adverse events in the MTD and toxicology studies. Moreover, no obvious pathologic changes were observed based on histology, hematology, serum biochemistry, or necropsy compared to placebo-treated controls. The PK study demonstrated a peak-blood concentration (Cmax) at 45 mins after oral administration of 2.24 and a serum half-life of 10 hours.ConclusionIn conclusion, CMC 2.24, orally administered to rats once a day, appears to be safe and effective at a wide range of doses, consistent with efficacy previously demonstrated in studies on animal models of various collagenolytic diseases, such as periodontitis, diabetes and cancer.

Impact of Antioxidant Therapy on Natural Pregnancy Outcomes and Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS. Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines. We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients. We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies. A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair. The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful.

Tolerance and Pharmacokinetics of Galliprant™ Administered Orally to Collies Homozygous for MDR1‐1Δ

The objectives of the study were to evaluate the pharmacokinetics and tolerance of grapiprant, a substrate of the human P‐gp transporter, in collies homozygous for MDR1‐1Δ when administered at the labeled dosage of 2 mg/kg once daily for 28 days. Twelve collie dogs with homozygous for MDR1‐1Δ genotype from a commercial colony were used in the study, eight in the treated group and four as placebo‐treated controls. The only treatment‐related clinical sign was self‐limiting vomiting (in 2/8 treated animals) and the only treatment‐related clinical pathological changes seen were a slight decrease in serum albumin in one dog (2.6 g/dL; reference 2.7 to 3.9 g/dL) and total protein (5.1 g/dL; reference 5.5 to 7.7 g/dL). Absorption of grapiprant was rapid with a median Tmax of 1 h, Cmax of 5.2 μg/mL, AUC0‐24 of 17.3 ± 7.1 h*μg/mL and median terminal t½ of 4.3 h after the first dose. To determine whether MDR1‐1Δ animals handle grapiprant differently from normal dogs, a population pharmacokinetic analysis was performed utilizing data from the collies and historical beagle data. Volume of the peripheral compartment of collies was estimated to be 45% that of beagles, and clearance from the central compartment was 71% less in collies than in beagles. Self‐liming vomiting events occurred at a numerically higher rate (2/8; 25%) in this group of P‐gp‐deficient dogs than seen in a clinical study (17%) composed of various dog breeds but limited numbers in this PK study make comparisons difficult. Grapiprant was otherwise well tolerated in collies homozygous for MDR1‐1Δ despite increased drug exposure compared to dogs without this mutation.

Comparative preventive efficacy of ProHeart\xae 12, Heartgard\xae Plus and Interceptor\xae Plus against a macrocyclic lactone-resistant strain (JYD-34) of heartworm (Dirofilaria immitis) in dogs

BackgroundThe current studies compared ProHeart® 12, Heartgard® Plus and Interceptor® Plus for preventive efficacy against JYD-34, a macrocyclic lactone (ML)-resistant strain of Dirofilaria immitis in dogs.MethodsIn two studies, each using 24 adult beagles, dogs were allocated to four treatment groups (n = 6): placebo-treated control; ProHeart 12 as per label (0.5 mg/kg moxidectin); Heartgard Plus (HGP) as per label (minimum 6 µg/kg ivermectin); and Interceptor Plus (INP) as per label (minimum 0.5 mg/kg milbemycin oxime). In both studies, ProHeart 12 was administered as a single subcutaneous dose on day 0, and HGP and INP were administered orally on days 0, 30, 60, 90, 120 and 150. In Studies 1 and 2, dogs were inoculated with 50 third-stage heartworm larvae (JYD-34 strain) on days −30 and 165, respectively. In Study 2, treatment for both HGP and INP was continued on days 180, 210, 240, 270, 300 and 330. Adult heartworm recoveries were performed on day 185 in Study 1 and on day 360 in Study 2.ResultsIn Studies 1 and 2, all placebo-treated dogs developed adult heartworm infections (geometric mean, 29.9 and 34.9 worms/dog, respectively). A single dose of ProHeart 12 was 100% effective in preventing the development of adult JYD-34 heartworms when treatment was initiated 30 days after heartworm inoculation, while six consecutive monthly doses of HGP and INP were only 10.5% and 14.6% effective, respectively. The mean worm count for the ProHeart 12-treated group was significantly lower (P < 0.0001) than that for the placebo control, HGP- and INP-treated groups. In Study 2, the dogs treated with ProHeart 12 had an efficacy of 98.3%. All dogs treated with HGP and INP for 12 consecutive months had adult heartworms with efficacies of 37.7% and 34.9%, respectively. The mean worm count for the ProHeart 12-treated dogs was significantly lower (P < 0.0001) than those for the control group, HGP- and INP-treated groups.ConclusionsA single administration of ProHeart 12 was 98–100% effective in preventing the development of the ML-resistant JYD-34 heartworm strain and was significantly better than multiple consecutive monthly doses of either Heartgard Plus or Interceptor Plus in both studies.Graphical

A field trial comparing four oral nonsteroidal anti-inflammatory drugs on controlling cautery dehorning pain and stress in calves

The purpose of this study was to compare the analgesic effect of four nonsteroidal anti-inflammatory drugs (NSAIDs) administered as a single, standardized, oral dose in dairy calves at the time of cautery dehorning. The NSAIDs investigated have pharmacokinetic properties in cattle that produce persistent plasma concentrations that may provide prolonged analgesia with the added practicality of a simple administration regimen. One hundred and eighty-five Holstein calves aged approximately 50 d old were either sham dehorned (n = 31) or cautery dehorned following oral administration of carprofen (n = 31), firocoxib (n = 31), flunixin meglumine (n = 30), meloxicam (n = 31) or placebo (n = 31) in a randomized, controlled trial. A standard dose of 2.0 mg/kg was administered to all calves receiving an oral NSAID. All calves received local anesthesia prior to actual or sham dehorning. Cortisol concentrations, heart rate, mechanical nociception thresholds, ocular and dehorning area temperatures, and average daily gains were evaluated. A linear mixed-effects model with repeated measures was used for statistical analysis. Administration of oral meloxicam, flunixin meglumine, and firocoxib at 2.0 mg/kg resulted in decreased cortisol concentrations compared to placebo-treated controls for the first 24 h postdehorning (AUEC0–24) (P = 0.03). Moreover, firocoxib, flunixin meglumine, and meloxicam attenuated the maximum cortisol concentrations compared to placebo-treated calves (P = 0.04, P= 0.02). In calves treated with flunixin meglumine, cortisol concentrations was reduced at 4 h (P = 0.04) and 8 h (P = 0.02). In addition, analgesic administration was associated with changes in ocular and dehorning area temperature differences (P = 0.09). Carprofen and meloxicam reduced heart rates during the entire study period (P = 0.003). Although a treatment effect (P < 0.0001) was observed in the determination of mechanical nociception threshold among all treatment groups, meloxicam expressed marginally significant effects (P = 0.09) among NSAID treated groups dehorned. A single dose of oral meloxicam, flunixin meglumine, or firocoxib administered at 2.0 mg/kg reduced the acute stress response associated with cautery dehorning. However, carprofen administration was associated with increased cortisol concentrations and dehorning area temperatures for the initial 24 h. Given the changes in pain and stress outcome variables assessed in this study, NSAIDs should be administered at the time of dehorning.

Effects of Chronic Supplementation of L-Arginine on Physical Fitness in Water Polo Players.

Background Ergogenic nutritional supplementation is sought by professional athletes for improving physical performance; nevertheless, scientific evidence to support the chronic use of L-Arginine among water polo players is missing. Methods Seventeen male professional water polo players were randomly assigned to assume 5 grams per day of L-Arginine (n = 9) or placebo (n = 8) for 4 weeks. The players' fitness level was assessed in the maximal speed swimming test. Ear lobe blood samples taken before and after the effort for serum lactate content were analyzed. A speed-to-lactate ratio was generated at the baseline and after 4 weeks of treatment. We also tested the effects of L-Arginine in vitro, measuring NO production, mitochondrial respiration, and gene expression in human fibroblasts. Results L-Arginine did not modify BMI, muscle strength, and maximal speed at 200 meters after 4 weeks. However, L-Arginine ameliorated oxidative metabolism to exercise as suggested by the statistically significant lower lactate-to-speed ratio, which was not observed in placebo-treated controls. In vitro, L-Arginine induced the expression of a key regulator of mitochondrial biogenesis (PGC1α) and genes encoding for complex I and increased the production of nitric oxide and the maximal oxygen consumption rate. Conclusions Chronic L-Arginine is safe and effective in ameliorating the oxidative metabolism of professional water polo players, through a mechanism of enhanced mitochondrial function.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel in cats against Toxocara cati and Dipylidium caninum.

NexGard® Combo, a novel topical antiparasitic product for cats, combines the insecticide/acaricide esafoxolaner with the nematocide eprinomectin and cestodicide praziquantel. The efficacy of this combination product was evaluated against two common endoparasites of global occurrence in cats, the nematode Toxocara cati and the cestode Dipylidium caninum, in five controlled studies using naturally or experimentally infected cats with parasites of North American, South African or European origin. Cats evaluated in these studies harbored patent infection of the target parasite confirmed through a pre-treatment fecal examination. In each study, cats were allocated randomly to two groups of equal size (8 or 10 cats per group per study), one group treated with a placebo (mineral oil) and the other with NexGard® Combo. Both treatments were administered once as a spot-on at 0.12 mL per kg body weight to deliver the minimum label dosage (1.44 mg/kg esafoxolaner, 0.48 mg/kg eprinomectin, and 10.0 mg/kg praziquantel) to the NexGard® Combo-treated cats. To determine efficacy, geometric mean parasite counts seven to 12 days after treatment of placebo-treated (control) cats and NexGard® Combo-treated cats were compared. The efficacy of NexGard® Combo was 98.8% and 100% against adult T. cati in two studies; and 98.0%, 98.3% and 93.2% against D. caninum in three studies. No adverse events related to treatment were observed throughout the studies. These studies demonstrate high efficacy against these major feline endoparasites and excellent acceptability of the novel topical antiparasitic combination of esafoxolaner, eprinomectin and praziquantel.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against ear mite (Otodectes cynotis) infestations in cats.

Esafoxolaner, a purified enantiomer of afoxolaner with insecticidal and acaricidal properties, is combined with eprinomectin and praziquantel, nematodicidal and cestodicidal compounds, in NexGard® Combo, a novel topical endectoparasiticide formulation for cats. The efficacy of this formulation was assessed against Otodectes cynotis in two laboratory studies conducted in South Africa and in the USA with local isolates, and in one field trial conducted in Europe. In each study, cats were randomly allocated to a placebo-treated control group and a novel formulation-treated group. In the laboratory studies, cats were treated at the minimum recommended dose; in the field trial, cats were treated at label dose. All included cats were diagnosed positive for O. cynotis prior to treatment by otoscopy. The main variable of efficacy was a comparison of the number of live O. cynotis collected in both ear canals of all cats in the treated and control groups, one month after treatment. Efficacy of the novel topical formulation exceeded 97% in the three studies. These studies demonstrated the high effectiveness of NexGard® Combo in cats for the treatment of O. cynotis infestations. No health abnormalities were attributed to the treatment in any of the studies.

Topical therapy with rhubarb navel plasters in patients with chronic constipation: Results from a prospective randomized multicenter study

Ethnopharmacological relevanceConstipation is a functional gastrointestinal disorder and one of the most prevalent conditions encountered in primary care settings. Rhubarb navel dressings have been used for more than 2,000 years in Chinese medicine to treat constipation. However, the effect of topical rhubarb administration has still not been well recognized and this strategy is not yet established as an evidence-based approach.Aim of the study: In this study, we performed a prospective multicentric randomized controlled trial to evaluate the efficacy and safety of rhubarb navel plasters for patients with chronic constipation. Materials and methodsA total of 374 patients from six teaching hospitals were prospectively included between 09/2016 and 10/2017 in the study based on Rome III criteria. All participants were randomly assigned (1:1) into verum/placebo group and given either Rheum officinale rhubarb powder or a placebo flour stick on the navel for 6 h/day/8 days. Primary outcome measures were the Cleveland Constipation Score (CCS) for the feces condition and Bristol Stool Scale (BSS) for stool consistency and 24 h defecation frequency. ResultsThe groups demonstrated no statistical differences in demographic data, clinical diagnoses and concomitant medication at baseline. In patients treated with the verum CCS was 5.61 (day 8, 95% CI 5.15–6.07) compared to 8.62 (95% CI 8.07–9.18) in placebo-treated controls (P < 0.001). The mean change of CCS at the end of treatment (day 8 versus [vs] day 0) was 6.04 in verum-treated vs 2.73 in placebo-treated controls (P < 0.001). Also 24 h defecation frequency (BSS) showed superior results (day 5: 0.84 vs 0.62, 95% CI 0.67–0.80, P < 0.001; day 6: 0.82 vs 0.60, 95% CI 0.64–0.78, P < 0.01 and day 8: 0.82 vs 0.60, 95% CI 0.64–0.78, P < 0.01) and better BSS type classification during treatment than controls (P < 0.05). No significant differences in adverse events between both groups became obvious. ConclusionRhubarb navel plaster administration over an 8-day-treatment period resulted in significantly improved bowel function as demonstrated by the CCS, 24 h defecating frequency and BSS. Our results suggest that rhubarb navel plasters represent a feasible, safe and efficient application route for the treatment of patients suffering from chronic constipation.

Efficacy and safety of biological agents in patients with giant cell arteritis: A meta-analysis of randomized trials.

This study assessed the efficacy and safety of biological agents in patients with giant cell arteritis (GCA). A meta-analysis of 6 randomized clinical trials (RCTs) (260 patients and 193 controls) to examine the efficacy and safety of tocilizumab, tumor necrosis factor (TNF) inhibitors, and abatacept relative to that of placebo in GCA patients was performed. The remission rate was significantly higher for tocilizumab-treated patients than that for placebo-treated controls (odds ratio (OR) 7.009, 95% confidence interval (CI) 3.854 - 12.75, p < 0.001). In addition, the relapse rate was significantly lower for the tocilizumab group than that for the placebo group (OR 0.222, 95% CI 0.129 - 0.381, p < 0.001). Further, no significant difference in remission and relapse was observed between groups treated with TNF inhibitors, abatacept, and placebo. The number of serious adverse events (SAEs) was significantly lower in tocilizumab-treated patients than that in placebo-treated controls (OR 0.539, 95% CI 0.296 - 0.982, p = 0.044). However, there was no significant difference in SAEs among patients treated with TNF inhibitors, abatacept, and placebo. The infection rate was significantly higher in TNF inhibitor-treated patients than in those treated with placebo (OR 2.407, 95% CI 1.168 - 4.960, p = 0.017), while there was no significant difference in infection rate between individuals treated with tocilizumab, abatacept, and placebo. Tocilizumab was found to be more effective than placebo in GCA patients, but TNF inhibitors and abatacept were not. Further, TNF inhibitors were associated with a higher risk of infection.

Effectiveness of low-level laser therapy for oral mucositis prevention in patients undergoing chemoradiotherapy for the treatment of head and neck cancer: A systematic review and meta-analysis.

Oral Mucositis is a frequent and debilitating inflammatory complication in patients with head and neck malignancies and may lead to unplanned treatment interruptions due to intense pain and dysphagia. This systematic review with meta-analysis was performed to determine the effectiveness of low-level laser therapy in preventing oral mucositis in this context. The following databases were searched through September 2018, with last search performed on May 2019, for clinical trials: MEDLINE via PubMed, Cochrane Central, Scopus, Lilacs, ISI Web of Science and SIGLE via Open Grey. From 14,525 records, 4 studies were included in the review and 3 studies were included in meta-analysis. Data from 500 patients (mean age of 53.595 and 54.14 for intervention and control groups, respectively) were analysed. Meta-analysis showed that laser therapy prevents oral mucositis incidence in 28% and 23% of cases during the third and fourth follow-up week, respectively, in comparison to a placebo-treated control group. There was no statistically significant difference the prevention of pain; dysphagia and quality of life were not analysed due to missing. Laser therapy was effective in preventing oral mucositis from the 15th to the 45th days of chemoradiotherapy. However, new primary studies with low risk of bias are needed so a higher scientific evidence can be obtained.

Effect of vaccination with a Mannheimia haemolyticasubunit vaccine on milk yield in lactating dairy cows

Vaccination of adult lactating dairy cattle can have a negative impact on milk production. Decreased milk production may occur from a combination of the cow’s immune response, endotoxin level in the vaccine, and the impact of cattle handling. A randomized clinical trial utilized 3 treatment groups to examine changes in milk production following vaccination with a Mannheimia haemolytica subunit vaccine (MHSV; Nuplura PH, Elanco Animal Health) using 972 lactating dairy cows on a single Midwestern dairy: a vaccinated group (MHSV, n=315); a placebo-treated control (saline, n=342); and a negative control group (no injections, n=315). The decline in milk across a 3 d post-treatment period for the saline group was 0.5 lb (0.2 kg) greater than the negative control cows, but the difference was not significant (P=0.57). The decline in milk during the same time period for cows in the MHSV group was 1.5 lb (0.7 kg) more than the negative control, (P=0.02). The declines between the saline group (0.5 lb; 0.2 kg) and the MHSV group (1.5 lb; 0.7 kg) were not significantly different (P=0.17).

Effects of recombinant bovine interleukin-8 (rbIL-8) treatment on health, metabolism, and lactation performance in Holstein cattle II: Postpartum uterine health, ketosis, and milk production

To evaluate the effect of recombinant bovine interleukin-8 (rbIL-8) on uterine health and milk production, 2 separate studies were conducted. For study 1, postpartum Holstein cows (n = 213) were randomly allocated into 1 of 3 intrauterine treatment groups: control (CTR, 250 mL of saline solution), low dose (L-IL8, 11.25 µg of rbIL-8 diluted in 250 mL of saline solution), and high dose (H-IL8, 1,125 µg of rbIL-8 diluted in 250 mL of saline solution). Intrauterine delivery of treatments was performed within 12 h of parturition. Cows were evaluated for retained fetal membranes, puerperal metritis, and clinical endometritis. Blood samples were collected immediately before treatment and 1, 2, and 3 d in milk for assessment of IL-8, haptoglobin, fatty acids, and β-hydroxybutyrate concentrations. Treatment with rbIL-8 reduced the incidence of puerperal metritis in multiparous cows (CTR = 34.3, L-IL8 = 8.11, and H-IL8 = 6.35%). Both the L-IL8 and H-IL8 groups produced significantly more milk, fat-corrected milk, and energy-corrected milk yields when compared with placebo-treated controls. A second study was performed to confirm the effect of rbIL-8 on milk production. In study 2, 164 primiparous cows were randomly allocated into 1 of 4 treatment groups: control (CTR, 250 mL of saline solution), low dose (L-IL8, 0.14 µg of rbIL-8), medium dose (M-IL8, 14 µg of rbIL-8), and high dose (H-IL8, 1,400 µg of rbIL-8). Treatments were prepared and administered as described for study 1. Cows in the L-IL8, M-IL8, and H-IL8 groups produced significantly more milk, fat-corrected milk, and energy-corrected milk yields when compared with control cows. In conclusion, treatment with rbIL-8 decreased the incidence of puerperal metritis in multiparous cows. The administration of rbIL-8 was repeatedly associated with a dramatic and long-lasting improvement of lactation performance.