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.     

Burn-Healing Effects of a Composition Containing Chitosan Gel and a Blood Serum Bioregulator

We studied the effect of combined preparation on the basis of chitosan containing a bioregulator isolated from cattle serum in a concentration of 10(-10) mg/ml on healing of II-IIIa degree skin burns in mammals in vivo.     

Study of Wound-Healing Activity of Bioregulators Isolated from Eye Tissues and Bovine Serum in the Model of Experimental Corneal Injury in Rabbits In Vivo

We compared wound-healing activity of bioregulators isolated from cattle cornea, serum, and retinal pigment epithelium on in vivo model of experimental corneal injury in rabbits. Bioregulators were instilled into the eye as solutions at a concentration corresponding to 10^-12 mg protein/ml. The animals were sacrificed on day 21 after injury and the corneas were examined histologically. The best wound-healing effect was produced by bioregulators isolated from the cornea and serum and instilled successively into rabbit eyes with an interval of 15-20 min twice a day: multicellular epithelium was observed in the wound, and slight inflammation, in the stroma.     

Experimental Models for Culturing of Eye Tissues of <Emphasis Type="Italic">Pleurodeles Waltl</Emphasis> for Evaluation of Specific Effects of Sclera Bioregulator in Ultra-Low Doses

Experiments on stationary culture of posterior eye and roll-bottle culture of the whole eye from adult water lizards Pleurodeles waltl showed that sclera bioregulator produces a stabilizing effects on adhesion interactions between the sclera, choroid, and pigment epithelium and on the maintenance of viability of sclera fi broblasts and pigment epithelium cells.     

Temporal variation in parasite infestation of a host individual: does a parasite-free host remain uninfested permanently?

Host individuals not infested by parasites at a given time are either permanently free from parasites or could be infested at other times. We studied temporal variation in the presence or absence of fleas (Siphonaptera) on individual rodents of two species (Gerbillus dasyurus and Acomys cahirinus) and questioned if and how an individual rodent can change its infestation status temporally. Change in infestation status by fleas over time was found in 45.5% of G. dasyurus and 35.9% of A. cahirinus. In both host species, the proportion of individuals that either changed or did not change their infestation status did not differ from the null expectation of 1:1. No difference between the proportions of infested at two consecutive captures and uninfested at two consecutive captures animals was found in A. cahirinus, whereas the proportion of G. dasyurus infested by fleas at two consecutive captures was significantly greater than that of uninfested at two consecutive captures individuals. In both host species, similar proportions of individuals changed their infestation status either from being infested to being uninfested or vice versa. Among individuals of both species that were initially infested by fleas, similar proportions changed and did not change their subsequent infestation status. The same was true for the uninfested at the first capture A. cahirinus. However, among initially uninfested G. dasyurus, the proportion of individuals that remained uninfested was significantly greater than that of the individuals newly infested by fleas. In A. cahirinus, the probability to change the infestation status did not depend on the initial status of an individual. In G. dasyurus, the probability of the initially uninfested individuals to be subsequently found still uninfested was higher than to be subsequently found harboring fleas, whereas initially infested individuals could be subsequently found either still infested or flea-free with equal probability.     

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.