Botulinum neurotoxin B (BoNT-B) mediates proteolytic cleavage of VAMP I/II (synaptobrevins I/II), which prevents vesicle-membrane fusion and blocks neurotransmitter release. In the present study, we investigated the effects of BoNT-B on neurotransmitter release in vivo from spinal primary afferent sensory fibers and the effects of this blockade on nociception. With intrathecally (IT) delivered BoNT-B in C57B/l6 mice, we characterized the effects of such block on the release of substance P (SP) from spinal afferent nociceptors (as measured by neurokinin-1 receptor, NK1-R, internalization), spinal neuronal activation (as indicated by spinal C-Fos expression) and nociceptive behavior after intraplantar (IPLT) formalin. In addition, we investigated the effect of IT BoNT-B on spinal nerve ligation-induced tactile allodynia. A single percutaneous IT injection of BoNT-B 0.5 U at 2 or 5 days prior to IPLT formalin reduced NK1-R internalization and C-Fos expression. These effects correlated with BoNT-B cleavage of VAMPI/II protein in tissue lysate. IT BoNT-B also produced a corresponding reduction in phase 2 of formalin-evoked flinching behavior for over 30 days after IT injection. In mice with spinal nerve ligation (SNL), tactile allodynia was observed, which was attenuated by IT BoNT-B 0.5 U over the next 15 days, as compared to vehicle animals. These effects were observed without effects upon motor function. The specificity of the IT BoNT-B effect is indicated by: i) IT co-injection of BoNT-B and anti-BoNTB antibody prevented effects on SP release, and ii) IT BoNT-B 50 U in the Sprague Dawley rats showed no effect on formalin-evoked flinching or SNL-induced tactile allodynia, which is consistent with rat resistance to BoNT-B. IT BoNT-B blocks transmitter release from spinal primary afferents, and attenuates inflammatory nociceptive response and spinal nerve injury-induced neuropathic pain, in the absence of motor impairment. These observations provide an initial assessment of the ability of IT BoNT-B to regulate spinal nociceptive processing.

IntroductionEmphysematous pyelonephritis (EPN) is a rare, life-threatening necrotizing infection of the kidney. The mortality rate for EPN is as high as 25%. We conducted a retrospective study at MS Ramaiah Hospital between January 2011 and May 2016 to observe the clinical, biochemical, and microbiological patterns of EPN at our institute.MethodsThe clinical and laboratory data, imaging findings, and microbiological patterns of 51 patients chosen for the study were recorded. The data were analyzed to identify the prognostic variables that could predict the morbidity and mortality of patients with EPN, and the focus of this study was to determine risk factors for and outcomes of patients who presented with EPN and who required hemodialysis. Primary endpoints were successful treatment and all-cause mortality. Secondary endpoints included need for hemodialysis and the need for a specific treatment.ResultsThere was an equal incidence among both sexes (median age: 59 years). Common symptoms were abdominal pain (94.11%), fever (83.2%), dysuria (74.5%), vomiting (72.54%), frequency of micturition (68.62%), oliguria, generalized weakness (66.67%), and breathlessness (66.67%); 98.03% (n = 50) of the patients had diabetes. The most common organism cultured was Escherichia coli (37.2%). Nineteen patients (37.2%) required dialysis; their mean age was 60.25 ± 11.74 years. Male sex, diabetes mellitus, shock, high serum creatinine at presentation, and uremic symptoms showed no statistically significant association. Indefinite hemodialysis was required by 12.5% of patients. The antibiotic-treated group had a 100% success rate, whereas the Double J (DJ) stenting group (Double J stent, Biorad, India) had 96.42% success rate.ConclusionEarly diagnosis and broad spectrum antibiotics, together with an appropriately timed intervention, resulted in decreased mortality. Pain in the abdomen and renal angle tenderness were the most common clinical finding. E coli was the most found organism, and early use of broad spectrum antibiotics decreased mortality.

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This MRI study illustrates the recently raised conjecture that MVO delays/inhibits infarct resorption (healing), accentuates LV hypertrophy and pathological remodeling.