Exploration of Nanoethosomal Transgel of Naproxen Sodium for the Treatment of Arthritis.

BACKGROUND: The present work aimed to develop an ethosomal gel of naproxen sodium for the amelioration of rheumatoid arthritis. OBJECTIVE: In the present work, we have explored the potential of ethosomes to deliver naproxen into deeper skin strata. Further, the anti-inflammatory efficacy of naproxen ethosomal formulation was assessed using the carrageenan-induced rat paw edema model. METHODS: Naproxen sodium nanoethosomes were prepared using different proportions of lipoid S100 (50mg-200mg), ethanol (20-50%) and water, and were further characterized on the basis of vesicle morphology, entrapment efficiency, zeta potential, in-vitro drug release and ex-vivo permeation studies. RESULTS: The optimized ethosomal formulation was found to have 129 ± 0.01 nm particle size, 0.295 Polydispersity Index (PDI), -3.29 mV zeta potential, 88% entrapment efficiency and 96.573% drug release in 24 hours. TEM and SEM analysis of the optimized formulation showed slightly smooth spherical structures. The Confocal laser scanning microscopy showed that ethosomes could easily infiltrate into deeper dermal layers (upto 104.9µm) whereas the hydroalcoholic solution of the drug could penetrate up to 74.9µm. Further, the optimized ethosomal formulation was incorporated into 1% carbopol 934 gel base and optimized wherein the transdermal flux was found to be approximately 10 times more than the hydroethanolic solution. Also, the in-vivo pharmacodynamic study of the optimized ethosomal gel exhibited a higher percentage inhibition of swelling paw edema than marketed diclofenac gel. CONCLUSION: The ethosomal gel was successfully developed and has shown the potential to be a good option for the replacement of conventional therapies of rheumatoid arthritis.

Effect of rhubarb (Rheum emodi) in primary dysmenorrhoea: a single-blind randomized controlled trial.

BACKGROUND: The aim of this study was to investigate and evaluate the efficacy of Rheum emodi in the management of primary dysmenorrhoea. METHODS: A randomized, single-blind, standard controlled trial compared efficacy of R. emodi against mefenamic acid on diagnosed subjects of primary dysmenorrhoea for three consecutive cycles. Experimental group (n=30) received capsules of R. emodi powder two times a day, two days before the expected date of menstruation, and continued first three days of menstruation, while control group (n=15) participants received mefenamic acid capsules three times a day on the same protocol. The primary outcome measures were reduced in severity and duration of pain, assessed by visual analogue scale (VAS) and verbal multidimensional scoring system (VMSS), and secondary outcome measures were overall improvement of dysmenorrhoea and improved in quality of life (QOL). Statistical analysis was done by repeated measures analysis of variance and Chi-square/Fisher Exact test. RESULTS: The menstrual pain was significantly decreased in both groups after three-cycle intervention. Significant changes were observed in VAS (p<0.001) and VMSS (p<0.001) in the experimental group. There is a significant (p<0.001) reduction in duration of pain in both the groups. Associated symptoms and QOL were markedly improved after treatment (p<0.001). CONCLUSIONS: It has been clear from the above result that R. emodi is an effective herb in alleviating symptoms of primary dysmenorrhoea. It can serve as an alternative treatment without any apparent side effects. These results deserve further investigations.

Tactile experience shapes prey-capture behavior in Etruscan shrews.

A crucial role of tactile experience for the maturation of neural response properties in the somatosensory system is well established, but little is known about the role of tactile experience in the development of tactile behaviors. Here we study how tactile experience affects prey capture behavior in Etruscan shrews, Suncus etruscus. Prey capture in adult shrews is a high-speed behavior that relies on precise attacks guided by tactile Gestalt cues. We studied the role of tactile experience by three different approaches. First, we analyzed the hunting skills of young shrews' right after weaning. We found that prey capture in young animals in most, but not all, aspects is similar to that of adults. Second, we performed whisker trimming for 3-4 weeks after birth. Such deprivation resulted in a lasting disruption of prey capture even after whisker re-growth: attacks lacked precise targeting and had a lower success rate. Third, we presented adult shrews with an entirely novel prey species, the giant cockroach. The shape of this roach is very different from the shrew's normal (cricket) prey and the thorax-the preferred point of attack in crickets-is protected by a heavy cuticle. Initially shrews attacked giant roaches the same way they attack crickets and targeted the thoracic region. With progressive experience, however, shrews adopted a new attack strategy targeting legs and underside of the roaches while avoiding other body parts. Speed and efficiency of attacks improved. These data suggest that tactile experience shapes prey capture behavior.

The neurobiology of Etruscan shrew active touch.

The Etruscan shrew, Suncus etruscus, is not only the smallest terrestrial mammal, but also one of the fastest and most tactile hunters described to date. The shrew's skeletal muscle consists entirely of fast-twitch types and lacks slow fibres. Etruscan shrews detect, overwhelm, and kill insect prey in large numbers in darkness. The cricket prey is exquisitely mechanosensitive and fast-moving, and is as big as the shrew itself. Experiments with prey replica show that shape cues are both necessary and sufficient for evoking attacks. Shrew attacks are whisker guided by motion- and size-invariant Gestalt-like prey representations. Shrews often attack their prey prior to any signs of evasive manoeuvres. Shrews whisk at frequencies of approximately 14 Hz and can react with latencies as short as 25-30 ms to prey movement. The speed of attacks suggests that shrews identify and classify prey with a single touch. Large parts of the shrew's brain respond to vibrissal touch, which is represented in at least four cortical areas comprising collectively about a third of the cortical volume. Etruscan shrews can enter a torpid state and reduce their body temperature; we observed that cortical response latencies become two to three times longer when body temperature drops from 36°C to 24°C, suggesting that endothermy contributes to the animal's high-speed sensorimotor performance. We argue that small size, high-speed behaviour and extreme dependence on touch are not coincidental, but reflect an evolutionary strategy, in which the metabolic costs of small body size are outweighed by the advantages of being a short-range high-speed touch and kill predator.

Cortical organization in the Etruscan shrew (Suncus etruscus).

Cortical organization in the Etruscan shrew is of comparative interest because of its small size and because the Etruscan shrew is an amazing tactile hunter. Here we investigated cortical organization in Etruscan shrews by electrophysiological mapping. We developed an anesthesia protocol for this very small mammal in which we combined massive application of local anesthesia, very slow induction of general anesthesia, and passive cooling. Under this anesthesia regime, we characterized auditory, visual, and somatosensory cortical responses. We found that large parts of shrew cortex respond to such stimuli. Of the responsive sites, a small fraction (∼14%) responded to visual stimuli in a caudally located region. Another small fraction of sites (∼11%) responded to auditory stimuli in a centrally located region. The majority of sites (∼75%) responded to tactile stimuli. We identified two topographically organized somatosensory areas with small receptive fields referred to as putative primary somatosensory cortex and putative secondary somatosensory cortex. In a posterior-lateral region that partially overlaps with piriform cortex, we observed large somatosensory receptive fields and often polysensory responses. In an anterior-lateral region that partially overlaps with piriform cortex, we observed large unimodal somatosensory receptive fields. Our findings demonstrate a remarkable degree of tactile specialization in Etruscan shrew cortex.

Tactile guidance of prey capture in Etruscan shrews.

Whereas visuomotor behaviors and visual object recognition have been studied in detail, we know relatively little about tactile object representations. We investigate a new model system for the tactile guidance of behavior, namely prey (cricket) capture by one of the smallest mammals, the Etruscan shrew, Suncus etruscus. Because of their high metabolic rate and nocturnal lifestyle, Etruscan shrews are forced to detect, overwhelm, and kill prey in large numbers in darkness. Crickets are exquisitely mechanosensitive, fast-moving prey, almost as big as the shrew itself. Shrews succeed in hunting by lateralized, precise, and fast attacks. Removal experiments demonstrate that both macrovibrissae and microvibrissae are required for prey capture, with the macrovibrissae being involved in attack targeting. Experiments with artificial prey replica show that tactile shape cues are both necessary and sufficient for evoking attacks. Prey representations are motion- and size-invariant. Shrews distinguish and memorize prey features. Corrective maneuvers and cricket shape manipulation experiments indicate that shrew behavior is guided by Gestalt-like prey descriptions. Thus, tactile object recognition in Etruscan shrews shares characteristics of human visual object recognition, but it proceeds faster and occurs in a 20,000-times-smaller brain.