Efficacy of afoxolaner (NexGard®) in preventing the transmission of Leishmania infantum and Dirofilaria immitis to sheltered dogs in a highly endemic area.

BACKGROUND: Leishmania infantum and Dirofilaria immitis are among the most important canine vector-borne pathogens (CVBPs) of zoonotic concern in Europe. In endemic areas for both of these CVBPs, the use of systemic ectoparasiticides, such as afoxolaner (NexGard®; Boehringer Ingelheim Animal Health), may have the potential for controlling these infections. The aim of this study was to assess, for the first time, the insecticidal efficacy of NexGard® in decreasing the transmission of D. immitis and L. infantum to sheltered dogs living in a hyperendemic area, compared to the year before treatment, as well as its impact on the abundance of mosquito and sand fly populations. METHODS: All dogs (n = 179) enrolled in the study were divided into two groups based on their infection status at enrollment: a non-infected group (G1) and an infected group (G2; infected with D. immitis, L. infantum or both). The study was conducted from March 2020 to March 2021. In order to exclude all animals infected with L. infantum and D. immitis before March 2020 (sampling time: T0), dogs in G1 were sampled in June (T1; i.e. T0 + 90 days) and in October 2020 (T2; i.e. T0 + 210 days). From March to September 2020, all animals (G1 and G2) were weighed and treated monthly with NexGard®. Animals in G1 were tested for the last time in March 2021 (T3; i.e. T0 + 330 days) for assessing post-treatment incidence rate of infection and prevention efficacy. RESULTS: The post-treatment incidence of D. immitis was 3.7% (1/27; 95% confidence interval [CI]: 0.2-18.1) and that of L. infantum was 3.6% (3/83; 95% CI: 1.0-10.1). Considering the annual incidence in 2019 and 2020, the protective efficacy against D. immitis and L. infantum infections was 94.2 and 64%, respectively. Of the female mosquitoes collected (n = 146), only one pool out of 50 tested positive for D. immitis DNA, whereas out of 1252 female Sergentomya minuta specimens collected, only four tested positive for L. infantum (0.3%). CONCLUSIONS: Afoxolaner is efficacious in decreasing the rate of transmission of both D. immitis and L. infantum; however, comparison of the pre- and post-treatment period demonstrated that there was a significant difference only in the seasonal incidences of D. immitis infection. Preventive measures are recommended throughout the year in endemic areas to reduce the risk of pathogen transmission to animals and humans.

Efficacy and safety of evocalcet in treatment of secondary hyperparathyroidism in chronic kidney disease on hemodialysis patients: A protocol for a systematic review and meta-analysis.

BACKGROUND: Secondary hyperparathyroidism (SHPT) have been associated with poor health outcomes in hemodialysis patients. The cinacalcet has popularized in clinic which has efficacy but more adverse events; the novel oral calcimimetic agents evocalcet has appeared in recent years. However, it is currently unknown whether evocalcet produces more beneficial effects and fewer adverse events in patients with SHPT. The aim of this systematic review is to estimate the safety and efficacy of evocacelt. METHODS: Only randomized controlled trials (RCT) will be included in MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, and PUBMED from July 2010 to July 2020. Two reviewers will screen, select studies, extract data, and assess quality independently. The methodological quality including the risk of bias of the included studies will be evaluated using a modified assessment form, which is based on Cochrane assessment tool. Review Manager 5.3 software will be used for heterogeneity assessment, generating funnel-plots, data synthesis, subgroup analysis, and sensitivity analysis. We will use GRADE system to evaluate the quality of our evidence. RESULTS: We will provide some more practical and targeted results investigating the effect and safety of evocalcet for SHPT on hemodialysis in the current meta-analysis. CONCLUSION: The stronger evidence about evocalcet effect and safety will be provided for clinicians and policymakers. ETHICS AND DISSEMINATION: Ethical approval will be unnecessary because the data being included in this systematic review come from published literature and there will be no concerns regarding privacy. Findings of this research will be disseminated in a peer-reviewed journal or conference presentations. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/N59RB.

Capillary electrophoresis method for the determination of (R)-dapoxetine, (3S)-3-(dimethylamino)-3-phenyl-1-propanol, (S)-3-amino-3-phenyl-1-propanol and 1-naphthol as impurities of dapoxetine hydrochloride.

A capillary electrophoresis method was developed and validated for the determination of the purity of dapoxetine with regard to the related substances (3S)-3-amino-3-phenylpropan-1-ol, (3S)-3-(dimethylamino)-3-phenylpropan-1-ol, 1-naphthol and the enantiomer (R)-dapoxetine. The separation was based on a dual selector system, which was optimized by a fractional factorial resolution V + design followed by a central composite face centered design with star distance 1 and Monte Carlo simulations for defining the design space. The optimized background electrolyte consisted of a 50 mM sodium phosphate buffer, pH 6.3, containing 45 mg/mL sulfated γ-cyclodextrin and 40.2 mg/mL 2,6-dimethyl-ß-cyclodextrin. Separations were carried out in a 23.5/32 cm, 50 µm fused-silica capillary employing a separation voltage of 9 kV at 15 °C. Following robustness testing using a Plackett-Burman design the method was validated according to the International Council on Harmonization guideline Q2(R1) in the range of 0.05-1.0% relative to the dapoxetine concentration. The method was applied to the analysis of drug substance and a commercial tablet. Data regarding the enantiomeric purity of dapoxetine obtained by the capillary electrophoresis assay were comparable to the data obtained by an enantioselective HPLC method.

Japanese Dermatological Association Guidelines: Guidelines for the treatment of acne vulgaris 2017.

The Guidelines for the Treatment of Acne Vulgaris of the Japanese Dermatological Association was first published in Japanese in 2008 and revised in 2016 and 2017. These guidelines (GL) indicate the standard acne treatments in Japan and address pharmaceutical drugs and treatments applicable or in use in Japan. In these GL, the strength of the recommendation is based on clinical evidences as well as availability in Japanese medical institutions. In the 2016 and 2017 GL, some of the clinical questions were revised, and other questions were added in accordance with approval of topical medicines containing benzoyl peroxide (BPO). Rather than monotherapies of antibiotics, the 2017 GL more strongly recommend combination therapies, especially fixed-dose combination gels including BPO in the aspects of pharmacological actions and compliance in the acute inflammatory phase to achieve earlier and better improvements. The 2017 GL also indicate to limit the antimicrobial treatments for the acute inflammatory phase up to approximately 3 months and recommend BPO, adapalene, and a fixed-dose combination gel of 0.1% adapalene and 2.5% BPO for the maintenance phase to avoid the emergence of antimicrobial-resistant Propionibacterium acnes. The 2017 GL also discuss rosacea, which requires discrimination from acne and a different treatment plan.

[Indoor air guide values for naphthalene and naphthalene-like compounds. Announcement of the German Ad-hoc Working Group on Indoor Guidelines of the Indoor Air Hygiene Committee and of the States' Supreme Health Authorities]. / Richtwerte für Naphthalin und Naphthalin-ähnliche Verbindungen in der InnenraumluftMitteilung der Ad-hoc-Arbeitsgruppe Innenraumrichtwerte der Kommission Innenraumlufthygiene und der Obersten Landesgesundheitsbehörden.

The German Ad-hoc Working Group on Indoor Guidelines of the Indoor Air Hygiene Committee and of the States' Supreme Health Authorities is issuing indoor air guide values to protect public health. Naphthalene is a potentially volatile two-ring hydrocarbon with a mothball-like odor. Indoor air contaminations usually originate from tar-containing building products, sometimes from the use of mothballs. In Germany, indoor air concentrations of naphthalene are usually low, near the detection limit (medians of about 0.001 mg/m3, 95th percentiles up to 0.004 mg/m3). Naphthalene-like volatile compounds have been defined to cover methyl- and dimethylnaphthalenes and tricyclic aromatic hydrocarbons (e.g., acenaphthene, acenaphthylene, anthracene, fluorene and phenanthrene). Though methylnaphthalenes and dimethylnaphthalenes usually show low indoor air concentrations, they have been suspected to add to the mothball-like odor. Tricyclic aromatic hydrocarbons mostly occur below 0.001 mg/m3 of indoor air. Against this background naphthalene is seen to be the key component of this group of substances in indoor air. No valid human data is available with respect to health effects of inhaled naphthalene. Based on animal data cytotoxic-inflammatory lesions in the rat nasal epithelium are regarded as the critical endpoint. In a subchronic inhalation study in rats (Dodd et al., Inhal Toxicol 24:70­79, 2012), minimal effects were observed following an exposure to 5 mg naphthalene/m3. From this study the Ad-hoc Working Group derived a chronic NAEC of 2.5 mg naphthalene/m3. Time scaling was considered by a factor of 5.6 extrapolating from 6 to 24 h and 5 to 7 days, a factor of 2 applied for the use of F344 rats instead of the more sensitive Sprague-Dawley rats. Incorporating an interspecies factor of 1, an intraspecies factor of 10 and a factor of 2 for insufficient data on the toxicity of naphthalene in children resulted in a precautionary value of 0.01 mg naphthalene/m3 and a hazard-based guide value of 0.03 mg naphthalene/m3. In the European Union, naphthalene has been classified as a suspected human carcinogen. In rats, carcinogenicity (nasal olfactory neuroblastoma) was seen at 53 mg naphthalene/m3. In contrast no valid human data on carcinogenicity of naphthalene is available. The Ad-hoc Working Group holds that the derived guide values sufficiently prevent cytotoxic-inflammatory effects of naphthalene and consequently from its long-term impacts such as potential carcinogenicity. This opinion is supported by a study of Meng et al. (Mutat Res 721:199­205, 2011) initially pointing to a missing primary genotoxicity of naphthalene. Only few data are available for health evaluation of naphthalene-like compounds. Therefore, the indoor air guide values for naphthalene are recommended by the Ad-hoc Working Group to be used as preliminary indoor air guide values for the sum of bicyclic and tricyclic aromatic hydrocarbons, too. Indoor air measurement of tricyclic aromatic hydrocarbons should be restricted to the occurrence of directly emitting building products such as asphalt floor coverings.

Determination of cinacalcet hydrochloride in human plasma by liquid chromatography-tandem mass spectrometry.

A sensitive and selective high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed to determine the cinacalcet hydrochloride in human plasma. The analyte was extracted from plasma samples using a 96-well plate automatic solid-phase extraction (SPE) device and chromatographed on an Inertsil SIL-150 (2.1 mm × 50 mm, i.d. 5 µm) column using acetonitrile-water-formic acid (90:10:1) as the mobile phase with an isocratic flow rate of 0.35 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). The method was validated over the concentration range of 0.1-25 ng/mL. The indicators of inter- and intra-day precision (RSD%) were all within 15.1%, and the accuracy (RE%) was within ± 15%. The lower limit of quantitation (LLOQ) was 0.1 ng/mL. The average extraction recovery was 51.7%, and the detection was not affected by the matrix. The method was successfully applied to a pharmacokinetic study of cinacalcet hydrochloride in healthy Chinese volunteers.

1-naphthyl phosphate: specifications for high-quality substrate for measuring prostatic acid phosphatase activity.

Ten lots of sodium 1-naphthyl phosphate were compared by spectrophotometry, high-performance liquid chromatography, and kinetic measurements of the activity of human prostatic acid phosphatase (EC 3.1.3.2) in serum. Two lots were readily identified as the 2-naphthyl phosphate salt by spectrophotometry and liquid chromatography. Four of the remaining eight lots of sodium 1-naphthyl phosphate met the following specifications: (a) sodium 1-naphthyl phosphate content greater than 80% by A286nm measurements (epsilon286nm1-NP = 5630 L.mol-1.cm-1) and by enzymic conversion to 1-naphthol (epsilon332nm1-N = 7560 L.mol-1.cm-1), (b) free 1-naphthol less than 3 mmol/mol, (c) inorganic phosphate less than 10 mmol/mol, and (d) the catalytic activity concentration greater than 98% maximum by absorbance assay and greater than 90% maximum by spectrofluorometric assay during simultaneous comparisons of several substrates. The need for detailed specifications and the testing of each batch of sodium 1-naphthyl phosphate is readily demonstrated by this study.