Polypeptide Modulators of TRPV1 Produce Analgesia without Hyperthermia

Transient receptor potential vanilloid 1 receptors (TRPV1) play a significant physiological role. The study of novel TRPV1 agonists and antagonists is essential. Here, we report on the characterization of polypeptide antagonists of TRPV1 based on in vitro and in vivo experiments. We evaluated the ability of APHC1 and APHC3 to inhibit TRPV1 using the whole-cell patch clamp approach and single cell Ca²⁺ imaging. In vivo tests were performed to assess the biological effects of APHC1 and APHC3 on temperature sensation, inflammation and core body temperature. In the electrophysiological study, both polypeptides partially blocked the capsaicin-induced response of TRPV1, but only APHC3 inhibited acid-induced (pH 5.5) activation of the receptor. APHC1 and APHC3 showed significant antinociceptive and analgesic activity in vivo at reasonable doses (0.01–0.1 mg/kg) and did not cause hyperthermia. Intravenous administration of these polypeptides prolonged hot-plate latency, blocked capsaicin- and formalin-induced behavior, reversed CFA-induced hyperalgesia and produced hypothermia. Notably, APHC3’s ability to inhibit the low pH-induced activation of TRPV1 resulted in a reduced behavioural response in the acetic acid-induced writhing test, whereas APHC1 was much less effective. The polypeptides APHC1 and APHC3 could be referred to as a new class of TRPV1 modulators that produce a significant analgesic effect without hyperthermia.     

Anaplasma phagocytophilum infection in a domestic cat in Finland: Case report

Background

Anaplasmosis is a vectorborne disease caused by the gram-negative bacterium Anaplasma phagocytophilum. This species displays positive tropism to granulocytes and can cause illness in several mammalian species, including cats, dogs, and humans. It is considered as an emerging disease in Europe. The clinical signs are nonspecific and include fever, lethargy, and inappetence. The most typical hematologic abnormality is thrombocytopenia. A tentative diagnosis can be made by detecting intracytoplasmic morulae inside neutrophils. The diagnosis is confirmed by PCR and serology in paired serum samples. A sample for PCR analysis should be taken before treatment. Anaplasmosis is treated with doxycycline.

Case presentation

A feline case of anaplasmosis is presented. The history, clinical presentation, diagnostics, treatment, and follow-up are discussed.

Conclusions

This case indicates that Anaplasma phagocytophilum infects cats in Finland. To provide accurate treatment, anaplasmosis should be listed as a differential diagnosis in cats suffering from acute febrile illness with previous tick exposure.     

Embryo transfer,a useful technique to be applied in small community farms?

The objective of this study was to determine if the technique of embryo transfer in cattle can be commercially feasible in a region situated in the humid tropics of Mexico. Twenty-six Bos taurus and twenty-six Bos indicus cows were estrous synchronized and superovulated to obtain a total of 80 embryos of both sub-species. Embryos were classified using stereoscopic microscopy based on established criteria. Nine dual-purpose farms situated in the tropics of Mexico were chosen to provide ten recipient cows each to transfer one embryo per cow. The females were transferred using a fixed-time protocol after verifying the presence of a corpus luteum on the seventh day after the end of hormonal treatment. Pregnancy diagnosis was carried out 28 days after embryo transfer by ultrasonography. Estimation of the cost was determined by calculating the expenses for preparation of the donor and embryo recovery, which were US 633 and US633 and US 589 for B. taurus and B. indicus, respectively. The cost of each embryo was determined considering the number of transferable embryos recovered, which was 3.8 on mean. The cost of each conception was calculated taking into account the percentage of pregnant animals (27% on mean), and the cost for preparing donor and recipient cows, for transferring embryo. The overall cost per gestation was US 1,447. Considering a 50:50 ratio of male to female born, the cost for a replacement heifer calf was US1,447. Considering a 50:50 ratio of male to female born, the cost for a replacement heifer calf was US 2,894, which surpassed by far the commercial cost of a crossbred ready-to-bred heifer normally used as replacement (approximately US $900).     

Seroprevalence and bacteremia [corrected] of Anaplasma phagocytophilum in cats from Bavaria and Lower Saxony (Germany)

Anaplasma (A.) phagocytophilum is a tick-transmitted obligate intracellular bacterium and has been identified in a wide range of mammalian species, causing febrile disease in some. Few reports show that it can also cause granulocytic anaplasmosis in cats. As data on the occurrence of A. phagocytophilum in cats from Germany is limited, a total of 326 serum and 306 EDTA-blood samples from cats from Germany were screened by direct (Giemsa-stained blood/buffy coat smears, real-time PCR) and indirect (IFAT) methods. Of 274 Giemsa-stained blood smears which could be evaluated none was positive for morulae, but one blood sample (< or =0.1%; 1/306) was positive for A. < or = phagocytophilum-DNA in PCR. Antibodies (cutoff > or = 1:64) were detected in 53 out of 326 samples (16.2%). Altogether, the results show a high seroprevalence rate of anti-A. phagocytophilum antibodies in cats in Germany while the low detection rate of this bacterial agent by direct methods is similar to those of other studies on A. phagocytophilum infections in cats.     

Isoflavonoid composition of a callus culture of the relict tree Maackia amurensis Rupr. et Maxim

Isoflavonoids, an interesting and restricted group of secondary metabolites of legumes, exhibit estrogenic, antiangiogenic, and anticancer activities and are now popular as dietary supplements. Plant cell cultures that possess an increased ability to synthesize these metabolites were examined. During the investigation, cell cultures of the Far Eastern relict tree Maackia amurensis (Leguminosae) were established. A selection of seed-derived cell aggregates yielded the callus line designated A-18. This culture produces 20 isoflavonoids, namely, the isoflavones genistein, daidzein, formononetin, calycosin, derrone, and pseudobaptigenin and their glycosylated conjugates genistin, 6'-O-malonylgenistin, ononin, 6'-O-malonylononin, daidzin, 3'-methoxydaidzin, 4'-O-beta-D-glucopyranosyldaidzin, 4'-O-beta-D-glucopyranosylgenistin, and 7-O-beta-D-glucopyranosylcalycosin; the pterocarpans maackiain and medicarpin and their glycosylated conjugates 6'-O-malonyl-3-O-beta-D-glucopyranosylmaackiain and 6'-O-malonyl-3-O-beta-D-glucopyranosylmedicarpin; and the new pterocarpan glucoside 6'-O-malonyl-3-O-beta-D-glucopyranosyl-6,6a-dehydromaackiain. These isoflavonoids, possessing a hepatoprotective activity, were stably produced by the A-18 calli for prolonged periods of observation.