Erythrocyte sedimentation rate and C‐reactive protein to monitor treatment outcomes in diabetic foot osteomyelitis

This study sought to evaluate the effectiveness of the inflammatory markers, erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP), in monitoring treatment of osteomyelitis in the diabetic foot. We screened 150 charts of patients admitted to our hospital with diabetic foot osteomyelitis (DFO), confirmed by positive results of bone culture and/or histopathology. We included patients who had an initial ESR/CRP within 72 hours of admission and two reported follow‐up values. We dichotomised patients based on the outcomes wound healing, re‐infection, recurrent ulceration, re‐hospitalisation, additional surgery, re‐amputation and death, all within 12 months, and analysed the trajectories of the markers over time. Our primary outcome, DFO remission, was defined as wound healing within 12 months of follow‐up without re‐infection. We included 122 subjects; 65 patients (53·3%) had a combination of positive culture and histopathology. Factors associated with DFO remission (n = 46) were a lower white blood count (WBC) at admission (P = 0·006) and a higher glomerular filtration rate (GFR, P = 0·049). Factors associated with healing were a lower WBC (P = 0·004), a higher GFR (P = 0·01), longer wound duration before admission (P = 0·01), location of the ulcer on the great toe (P = 0·01) and higher glycated haemoglobin (P = 0·03). Logistic regression analysis demonstrated no associations between DFO remission and other variables collected. Trajectories of the inflammatory markers showed an association between stagnating values of ESR and CRP and poor clinical outcomes. In this study population, the trajectories of both ESR and CRP during 12 months follow‐up suggest a predictive role of both inflammatory markers when monitoring treatment of DFO.     

Safety evaluation of Eugenia jambolana seed extract

ObjectiveTo evaluate the safety of ethanolic seed extract of Eugenia jambolana (EJSE) using acute and sub-chronic toxicity assays in Swiss albino mice as per Organisation for Economic Co-operation and Development (OECD) guidelines.MethodsPossible behavioral changes and lethality were observed in mice administered a single dose [1 000, 2 000, 3 000, 4 000 or 5 000 mg/kg body weight (BW)] of EJSE. Plasma levels of metabolic, hepatic, cardiac and renal function markers, electrolytes, blood count and histopathology of major organs were monitored in mice chronically treated with EJSE (1 000, 2 000 or 3 000 mg/kg BW) for 28 days.ResultsSince no mortality was recorded in the acute toxicity evaluation up to a dose of 5 000 mg/kg bodyweight of EJSE, 50% lethal dose (LD₅₀) was assumed to be > 5 000 mg/kg BW. In the sub-chronic toxicity evaluation, no adverse observations were recorded in mice administered with 2 000 mg/kg BW of EJSE; however at 3 000 mg/kg BW dose, moderately significant increase in the plasma levels of urea and creatinine was observed. Hence, the lowest observable adverse effect level (LOAEL) for EJSE was found to be 3 000 mg/kg BW and the no observable adverse effect level (NOAEL) was adjudged as 2 000 mg/kg BW.ConclusionsIt can be concluded from this study that, orally administered EJSE is safe up to a 10 fold higher dose than its reported therapeutic dose.     

Efficacy of 3,5-dibromo-L-phenylalanine in rat models of stroke,seizures and sensorimotor gating deficit

Background and purpose:

Abnormal glutamatergic activity is implicated in neurologic and neuropsychiatric disorders. Selective glutamate receptor antagonists were highly effective in animal models of stroke and seizures but failed in further clinical development because of serious side effects, including an almost complete set of symptoms of schizophrenia. Therefore, the novel polyvalent glutamatergic agent 3,5-dibromo-L-phenylalanine (3,5-DBr-L-Phe) was studied in rat models of stroke, seizures and sensorimotor gating deficit.

Experimental approach:

3,5-DBr-L-Phe was administered intraperitoneally as three boluses after intracerebral injection of endothelin-1 (ET-1) adjacent to the middle cerebral artery to cause brain injury (a model of stroke). 3,5-DBr-L-Phe was also given as a single bolus prior to pentylenetetrazole (PTZ) injection to induce seizures or prior to the administration of the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) to cause disruption of prepulse inhibition (PPI) of startle (sensorimotor gating deficit).

Key results:

Brain damage caused by ET-1 was reduced by 52%, which is comparable with the effects of MK-801 in this model as reported by others. 3,5-DBr-L-Phe significantly reduced seizures induced by PTZ without the significant effects on arterial blood pressure and heart rate normally caused by NMDA antagonists. 3,5-DBr-L-Phe prevented the disruption of PPI measured 3 days after the administration of ET-1. 3,5-DBr-L-Phe also eliminated sensorimotor gating deficit caused by MK-801.

Conclusion and implications:

The pharmacological profile of 3,5-DBr-L-Phe might be beneficial not only for developing a therapy for the neurological and cognitive symptoms of stroke and seizures but also for some neuropsychiatric disorders.     

Treatment of children with neurogenic bladder dysfunctions using dynamic nero-electrostimulation(DENS) and M-Cholinolytic therapy

【Objective】 To investigate effects of combined usage of dynamic neuro-electric stimulation(DNES) and M-cholynolytic therapy(oxybutynin) upon manifestations of neurogenic bladder dysfunctions(NBD) in children.【Method】 Urodynamics examination included registration of extemporaneous urinary excretion,urofluometry,and retrograde cytometry in horizontal and vertical position by example of urodynamic system(UDS) ACS 180 Plus(MENFIS BioMed.,USA).In accordance to severity of clinician manifestations,three groups of patients have been defined(27-highest one,49-middle and 51 low levels).Dynamic neuro-electrostimulation(DNES) procedures were conducted using the"DiaDNES-PKM"device(Russian Federation).The children were exposed to juxtaspinal stimulation on S1-S3 level-altogether 10 sessions have been performed.Oxybutynin(driptan) was used in dosage of 2.5 mg per diem.【Result】It was established that combined usage of DNES and oxybutynin in the group with highest severity caused the reduction of manifestations by 3.1 times while separately given DNES and basic therapy were followed by 34.1% and 28.0% reduction correspondently.Meanwhile,DNES and oxybutynin reduced severity in patients with pronounced disturbances by 7.5 times.Combined usage of oxybutynin and DNES in severely manifested NBD increased the effective volume of bladder by 2.3 times.Also significant reduction of both intrabladder pressure(by 48.0%) and compliance of the bladder(by 4.8 times) were detected under condition of combined usage of DNES and oxybutynin.All mentioned indices were modified to less extent in case of separate usage of DNES or oxybutynin when compared with the one registered after the combined their usage(P <0.05).【Conclusion】Combined usage of DENS and oxybutinin(driptan) is effective in most severe cases in children suffered from neurogenic overactive bladder.