Single-Dose P2 X4R Single-Chain Fragment Variable Antibody Permanently Reverses Chronic Pain in Male Mice.

Non-opioid single-chain variable fragment (scFv) small antibodies were generated as pain-reducing block of P2X4R receptor (P2X4R). A panel of scFvs targeting an extracellular peptide sequence of P2X4R was generated followed by cell-free ribosome display for recombinant antibody selection. After three rounds of bio-panning, a panel of recombinant antibodies was isolated and characterized by ELISA, cross-reactivity analysis, and immunoblotting/immunostaining. Generated scFv antibodies feature binding activity similar to monoclonal antibodies but with stronger affinity and increased tissue penetrability due to their ~30% smaller size. Two anti-P2X4R scFv clones (95, 12) with high specificity and affinity binding were selected for in vivo testing in male and female mice with trigeminal nerve chronic neuropathic pain (FRICT-ION model) persisting for several months in untreated BALBc mice. A single dose of P2X4R scFv (4 mg/kg, i.p.) successfully, completely, and permanently reversed chronic neuropathic pain-like measures in male mice only, providing retention of baseline behaviors indefinitely. Untreated mice retained hypersensitivity, and developed anxiety- and depression-like behaviors within 5 weeks. In vitro P2X4R scFv 95 treatment significantly increased the rheobase of larger-diameter (>25 µm) trigeminal ganglia (TG) neurons from FRICT-ION mice compared to controls. The data support use of engineered scFv antibodies as non-opioid biotherapeutic interventions for chronic pain.

Comparative Evaluation of the Efficacy and Onset of Local Anesthesia Using Buffered 2% Lidocaine with 1:100,000 Adrenaline, Non-buffered 2% Lidocaine with 1:100,000 Adrenaline, Buffered 4% Articaine with 1:100,000 Adrenaline and Non-buffered 4% Articaine with 1:100,000 Adrenaline in Dental Extraction.

Aim: To compare the efficacy and onset of local anesthesia using buffered versus non-buffered 2% lidocaine with 1:100,000 adrenaline and 4% articaine with 1:100,000 adrenaline in dental extraction. Methodology: A prospective, clinical study was carried out in oral and maxillofacial surgery department. Twenty-eight patients were considered in the study and were divided into 4 groups. Each group randomly received either buffered 2% lidocaine with 1:100,000 adrenaline, non-buffered 2% lidocaine with 1:100,000 adrenaline, buffered 4% articaine with 1:100,000 adrenaline or non-buffered 4% articaine with 1:100,000 adrenaline. The outcome variable was onset of anesthesia and effectiveness of anesthesia in buffered and non-buffered group. Results: Results showed that the mean onset of time and efficacy of local anesthesia was significantly better in buffered when compared with non-buffered local anesthetic solution with adrenaline. Conclusion: In conclusion, the addition of sodium bicarbonate as a buffering agent decreases time of onset and increases the effectiveness of local anesthetics, thus providing comfort to the patient. The mean onset of time for first symptom as well as lip numbness was more for non-buffered lidocaine followed by non-buffered articaine, buffered lidocaine and buffered articaine. The mean onset of time for subjective and objective symptoms was more for non-buffered anesthetic solution as compared to buffered anesthetic solution. VAS readings were not statistically significant among the four groups.

Eight Genome Sequences of Cluster BE1 Phages That Infect Streptomyces Species.

Cluster BE1 Streptomyces bacteriophages belong to the Siphoviridae, with genome sizes over 130 kbp, and they contain direct terminal repeats of approximately 11 kbp. Eight newly isolated closely related cluster BE1 phages contain 43 to 48 tRNAs, one transfer-messenger RNA (tmRNA), and 216 to 236 predicted open reading frames (ORFs), but few of their genes are shared with other phages, including those infecting Streptomyces species.

Genome Sequences of Five Streptomyces Bacteriophages Forming Cluster BG.

Cluster BG of the actinobacteriophage was formed upon discovery of five novel bacteriophages isolated by enrichment from their host, Streptomyces griseus subsp. griseus strain ATCC 10137. Four members of this cluster (BabyGotBac, Maih, TP1605, and YDN12) share over 89% average nucleotide identity, while the other (Xkcd426) has only 72% similarity to other cluster members.