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MOUSE ANTI GUINEA PIG B CELL SUBSET

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[#ABS12119] MOUSE ANTI GUINEA PIG B CELL SUBSET

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(1) Preclinical pharmacokinetic evaluation to facilitate repurposing of tyrosine kinase inhibitors nilotinib and imatinib as antiviral agents.[TOP]

Pubmed ID :30514402
Publication Date : //
Several tyrosine kinase inhibitors (TKIs) developed as anti-cancer drugs, also have anti-viral activity due to their ability to disrupt productive replication and dissemination in infected cells. Consequently, such drugs are attractive candidates for "repurposing" as anti-viral agents. However, clinical evaluation of therapeutics against infectious agents associated with high mortality, but low or infrequent incidence, is often unfeasible. The United States Food and Drug Administration formulated the "Animal Rule" to facilitate use of validated animal models for conducting anti-viral efficacy studies.

Authors : Ananthula Hari Krishna, Parker Scott, Touchette Erin, Buller R Mark, Patel Gopi, Kalman Daniel, Salzer Johanna S, Gallardo-Romero Nadia, Olson Victoria, Damon Inger K, Moir-Savitz Tessa, Sallans Larry, Werner Milton H, Sherwin Catherine M, Desai Pankaj B,



(2) Evaluation of the anti-asthmatic and antitussive potentials of methanol leaf extract of Napoleona vogelii in rodents.[TOP]

Pubmed ID :30396068
Publication Date : //
Napoleona vogelii is used in ethnomedicine for the treatment of asthma and cough. This study evaluated antiasthmatic and antitussive properties of its methanol leaf extract (NVE) in rodents. Phytochemical screening was conducted using established methods. Acute oral toxicity test was done in mice and guinea pigs. Ovalbumin (OA)-sensitized guinea pigs were orally pretreated with 100, 200 or 400 mg/kg/day of NVE or 0.5 mg/kg/day of salbutamol for 14 days before exposure to 0.2% histamine aerosol. Latency to preconvulsive dyspnea (PCD), tracheal fluid volume (TFV), flow rate (FR), and tracheal morphometry (TM) were evaluated. Tracheal rings from sensitized guinea pigs were tested in organ baths for antispasmodic and spasmolytic effects. Citric acid and ammonium hydroxide cough models were used to evaluate antitussive effects in guinea pigs and mice respectively. Tannins, alkaloids, flavonoids, and phenolic substances were found in NVE. LD values in mice and guinea pigs were greater than 5000 mg/kg. NVE caused a significant (P < 0.05) increase in the latency to PCD and a decrease in TFV in the group treated with 200 mg/kg. TM indicated a reduction in airway narrowing in NVE-treated groups. The presence of NVE significantly attenuated responses of tracheal rings to carbachol. Its addition to carbachol precontracted rings resulted in significant relaxation. E for calcium concentration-response was significantly (P < 0.01) decreased in the presence of NVE. Cough bouts dose-dependently decreased significantly (P < 0.05) in guinea pigs and mice. We conclude that NVE seems safe and possesses anti-asthmatic effect that involves inhibition of calcium influx. It also has antitussive properties that may be peripherally mediated.

Authors : Adejayan Adesola A, Ozolua Raymond I, Uwaya Dickson O, Eze Gerald I, Ezike Adaobi C,



(3) Functional mechanism of tracheal relaxation, antiasthmatic, and toxicological studies of 6-hydroxyflavone.[TOP]

Pubmed ID :30394554
Publication Date : //
Preclinical Research & Development Previously, we described tracheal rat rings relaxation by several flavonoids, being 6-hydroxyflavone (6-HOF) the most active derivative of the series. Thus, its mechanism of action was determined in an ex vivo tracheal rat ring bioassay. The anti-asthmatic effect was assayed in in vivo OVAlbumin (OVA)-sensitized guinea pigs. Finally, the toxicological profile of 6-HOF was studied based on Organization of Economic Cooperation and Development guidelines with modifications. 6-HOF-induced relaxation appears to be related with receptor-operated calcium channel and voltage-operated calcium channel blockade as the main mechanism of action, and also through the production of relaxant second messengers NO and cGMP. Molecular docking supports that 6-HOF acts as calcium channel blocker and by activation of nitric oxide synthase. In addition, the in vivo anti-asthmatic experiments demonstrate the dose-dependent significant anti-allergic effect of 6-HOF induced by OVA, with best activity at 50 /kg. Finally, toxicological studies determined a LD50 > 2,000 mg/kg and, after 28 day of treatment with 6-HOF (50 mg/kg) by intragastric route, mice did not exhibit evidence of any significant toxicity. In conclusion, experiments showed that 6-HOF exerts significant relaxant activity through calcium channel blockade, and possibly, by NO/cGMP-system stimulation on rat trachea, which interferes with the contraction mechanism of smooth muscle cells in the airways. In addition, the flavonoid shows potential anti-asthmatic properties in an anti-allergic pathway. Furthermore, because the pharmacological and safety evidence, we propose this flavonoid as lead for the development of a novel therapeutic agent for the treatment of asthma and related respiratory diseases.

Authors : Flores-Flores Angélica, Estrada-Soto Samuel, Millán-Pacheco César, Bazán-Perkins Blanca, Villalobos-Molina Rafael, Moreno-Fierros Leticia, Hernández-Pando Rogelio, García-Jiménez Sara, Rivera-Leyva Julio César,



(4) Virus-like particles of recombinant PCV2b carrying FMDV-VP1 epitopes induce both anti-PCV and anti-FMDV antibody responses.[TOP]

Pubmed ID :30338355
Publication Date : //
Mixed infection of porcine circovirus type 2 (PCV2) and foot-and-mouth disease virus (FMDV) is devastating to swine populations. To develop an effective vaccine that can protect the pigs from the infection of PCV2 and FMDV, we used the neutralizing B cell epitope region (aa 135-160) of FMDV to replace the regions aa 123-151 and aa 169-194 of the PCV2b Cap protein to generate a recombinant protein designated as Capfb. The Capfb protein was expressed in Escherichia coli system and the purified Capfb protein assembled into virus-like particles (VLPs) through dialysis. The ability of the Capfb protein to induce effective immune response against FMDV and PCV2b was tested in mice and guinea pigs. The results showed that the Capfb-VLPs could elicit anti-PCV2b and anti-FMDV antibody response in mice and guinea pigs without inducing antibodies against decoy epitope. Moreover, the Capfb-VLPs could enhance the percentage and activation of B cells in lymph nodes when the mice were stimulated with inactivated FMDV or PCV2b. These data suggested that the Capfb-VLPs could be an efficacious candidate antigen for developing a novel PCV2b-FMDV bivalent vaccine.

Authors : Li Xin, Meng Xiuping, Wang Shengnan, Li Zhiqin, Yang Lei, Tu Liqun, Diao Wenzhen, Yu Cheng, Yu Yongli, Yan Chaoying, Wang Liying,



(5) Connexin 30.2 is expressed in exocrine vascular endothelial and ductal epithelial cells throughout pancreatic postnatal development.[TOP]

Pubmed ID :30100173
Publication Date : //
Previously we have demonstrated that the GJ protein connexin 30.2 (Cx30.2) is expressed in pancreatic beta cells and endothelial cells (ECs) of the islet. In the present study, we address whether Cx30.2 is expressed in the exocrine pancreas, including its vascular system. For this, adult mouse pancreatic sections were double labeled with specific antibodies against Cx30.2 and CD31, an endothelial cell marker, or with anti-α-actin smooth muscle, a smooth muscle cell (SMC) marker or anti-mucin-1, a marker of epithelial ductal cells, using immunofluorescence (IF) studies. Cx30.2-IF hot spots were found at junctional membranes of exocrine ECs and SMCs of blood vessels. Furthermore, Cx30.2 was localized in mucin-1 positive cells or epithelial ductal cells. Using immunohistochemistry (IHC) studies, it was found that in vessels and ducts of different diameters, Cx30.2 was also expressed in these cell types. In addition, it was found that Cx30.2 is already expressed in these cell types in pancreatic sections of 3, 14 and 21 days postpartum. Moreover, this cell specific pattern of expression was also found in the adult rat, hamster and guinea pig pancreas. Expression of Cx30.2 mRNA and protein in the pancreas of all these species was confirmed by RT-PCR and Western blot studies. Overall, our results suggest that intercellular coupling mediated by Cx30.2 intercellular channels may synchronize the functional activity of ECs and SMCs of vascular cells, as well as of epithelial ductal cells after birth.

Authors : Coronel-Cruz C, Sánchez I, Hernández-Tellez B, Rodríguez-Mata V, Pinzón-Estrada E, Castell-Rodríguez A, Pérez-Armendariz E M,



(6) Protective role of specific murine antibodies in inhibiting systemic proliferation of virulent strain 544 in mice and guinea pig.[TOP]

Pubmed ID :30034172
Publication Date : //
The major objective of the investigation was to evaluate the hitherto uncharacterized potential of -specific antibodies to win the battle against virulent infection.

Authors : Verma Suman, Rawat Mayank, Kumawat Sanjay, Qureshi Salauddin, Mohd Gulam, Tiwari Ashok Kumar,



(7) Delamanid: From discovery to its use for pulmonary multidrug-resistant tuberculosis (MDR-TB).[TOP]

Pubmed ID :30029909
Publication Date : //
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is the leading cause of death from an infectious disease globally. The widespread and ever-increasing resistance to TB drugs is reducing the effectiveness of treatment and jeopardizing TB control. New effective drugs with acceptable safety profiles are needed to turn the tide. Since the early 1990s, Otsuka Pharmaceutical Co., Ltd. has had a TB drug development program that resulted in the selection and development of delamanid (OPC-67683, Deltyba), a first-in-class bicyclic nitroimidazole. Delamanid was initially approved by the European Medicines Agency (EMA) in 2014 for the treatment of adult pulmonary multi-drug resistant (MDR)-TB when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability. It has since been approved by several other countries/regions. In this review, we describe the history of delamanid's development, including the screening process, in vitro and in vivo characterization, as well as various clinical studies. Delamanid possesses potent activity against replicating, dormant, and intracellular MTB bacilli, and is bactericidal in mouse and guinea pig TB models. Delamanid resistance mechanisms have been attributed to genes in the F-dependent deazaflavin nitroreductase bio-activation pathway, found in mycobacterium species but not in common bacterial or mammalian cells. Published susceptibility testing results from 744 clinical isolates from delamanid-naïve patients indicate that the natural resistance rate to delamanid is very low (1.3%). Delamanid is largely metabolized by albumin in serum, and to a much less extent by cytochrome P enzymes. Furthermore, it neither inhibits nor induces P450 enzymes. In terms of efficacy, delamanid demonstrated activity in an early bactericidal activity trial in drug susceptible pulmonary TB patients and increased 2-month sputum culture conversion rates when added to an optimized background regimen in MDR-TB patients in a phase 2b global clinical trial. In addition, recent results outside clinical studies show favourable responses in highly resistant TB patients including extensively drug resistant (XDR)-TB when treated with delamanid-containing regimens in routine programmatic settings. The primary safety concern with delamanid is QTcF interval prolongation, although this observation has thus far not been associated with any clinical cardiac events. Overall, delamanid appears to be a well-tolerated and safe anti-TB drug when compared to other drugs used to treat MDR-TB.

Authors : Liu Yongge, Matsumoto Makoto, Ishida Hidekaza, Ohguro Kinue, Yoshitake Masuhiro, Gupta Rajesh, Geiter Lawrence, Hafkin Jeffrey,



(8) Comparative Study Between Low Level Laser and Therapeutic Ultrasound in Second Intention Ulcers Repair in Mice.[TOP]

Pubmed ID :30026899
Publication Date : //
An ulcer is an injury that affects the skin and has many causes. Healing is a way of protecting the body against any infectious agent that tries to infect you through the wound. Low level laser (LLL) in the treatment of ulcers, aims at maintaining the stability of the physiological process of tissue repair and ultrasound (US) acts by increasing the elasticity of tissue and scarring. The aim of this study was to analyze the effects of LLL and US in wound healing of ulcers induced in mice. In this experimental study, a sample of 36 guinea pigs was divided into 6 groups of 6 mice, 2 groups as control (C7) and (C14), 2 treated with laser (GL7) and (GL14) and the others 2 treated with ultrasound (GU7) and (GU14). The ulcer was induced and after 7 days, 6 mice from each group were sacrificed to obtain the histological sections for analysis, and the remaining 6 mice from each group continued under treatment and in day 14, they were sacrificed to obtain histologic specimens while macroscopic image was also carried out. Three aspects were analyzed, the percentage of wound regression where it was observed that there was a significant difference in the first 7 days. Regarding the inflammatory process, it was observed that in the first 7 days GL7 and GU7 improved significantly and within 14 days of the experimental period GU14 showed a significant difference when compared to C14. The number of fibroblasts present in the GL at 7 days showed a significant difference compared to the others, and at 14 days, the US group had a significant difference compared to the other groups. Thus, it was evident that the US had more effective results with anti-inflammatory action, better organization and increased deposition of collagen and fibroblasts. Therefore, it can be concluded that other studies are consistent with this taking into account the laser must be used during the early days of the initial healing process and the US during the end of this process.

Authors : de Sousa Aline Carla Teles, da Rocha Ítalo Bruno Paiva, de Carvalho Ana Flávia Machado, de Freitas Coelho Nayana Pinheiro Machado, Feitosa Maura Cristina Porto, Barros Esmeralda Maria Lustosa, Arisawa Emilia Angela Lo Schiavo, de Amorim Maria Rosilândia Lopes,



(9) Anti-allergy and anti-tussive activity of Clitoria ternatea L. in experimental animals.[TOP]

Pubmed ID :29787795
Publication Date : //
Clitoria ternatea flower is traditionally used in the treatment of respiratory disorders including bronchitis and is one of the ingredients in different Ayurvedic preparations that are used in respiratory disorders. However, till date there is no scientific report on the anti-asthmatic activity of this flower.

Authors : Singh Niraj Kumar, Garabadu Debapriya, Sharma Priyanka, Shrivastava Sushant Kumar, Mishra Pradeep,



(10) Tissue Distribution of Kir7.1 Inwardly Rectifying K Channel Probed in a Knock-in Mouse Expressing a Haemagglutinin-Tagged Protein.[TOP]

Pubmed ID :29740340
Publication Date : //
Kir7.1 encoded by the gene in the mouse is an inwardly rectifying K channel present in epithelia where it shares membrane localization with the Na/K-pump. Further investigations of the localisation and function of Kir7.1 would benefit from the availability of a knockout mouse, but perinatal mortality attributed to cleft palate in the neonate has thwarted this research. To facilitate localisation studies we now use CRISPR/Cas9 technology to generate a knock-in mouse, the Kir7.1-HA that expresses the channel tagged with a haemagglutinin (HA) epitope. The availability of antibodies for the HA epitope allows for application of western blot and immunolocalisation methods using widely available anti-HA antibodies with WT tissues providing unambiguous negative control. We demonstrate that Kir7.1-HA cloned from the choroid plexus of the knock-in mouse has the electrophysiological properties of the native channel, including characteristically large Rb currents. These large Kir7.1-mediated currents are accompanied by abundant apical membrane Kir7.1-HA immunoreactivity. WT-controlled western blots demonstrate the presence of Kir7.1-HA in the eye and the choroid plexus, trachea and lung, and intestinal epithelium but exclusively in the ileum. In the kidney, and at variance with previous reports in the rat and guinea-pig, Kir7.1-HA is expressed in the inner medulla but not in the cortex or outer medulla. In isolated tubules immunoreactivity was associated with inner medulla collecting ducts but not thin limbs of the loop of Henle. Kir7.1-HA shows basolateral expression in the respiratory tract epithelium from trachea to bronchioli. The channel also appears basolateral in the epithelium of the nasal cavity and nasopharynx in newborn animals. We show that HA-tagged Kir7.1 channel introduced in the mouse by a knock-in procedure has functional properties similar to the native protein and the animal thus generated has clear advantages in localisation studies. It might therefore become a useful tool to unravel Kir7.1 function in the different organs where it is expressed.

Authors : Cornejo Isabel, Villanueva Sandra, Burgos Johanna, López-Cayuqueo Karen I, Chambrey Régine, Julio-Kalajzić Francisca, Buelvas Neudo, Niemeyer María I, Figueiras-Fierro Dulce, Brown Peter D, Sepúlveda Francisco V, Cid L P,