Evaluating the inhibitory potential of Withania somnifera on platelet aggregation and inflammation enzymes: An in vitro and in silico study

Context Withania somnifera (L.) Dunal is traditionally used for treating various ailments, but lacks scientific evaluation.

Objective This study evaluates Withania somnifera (WS) for its effect on platelet activity and inflammatory enzymes.

Materials and methods Aqueous and ethanolic (1:1) leaf extracts were subjected to in vitro indirect haemolytic activity using Naja naja venom, human platelet aggregation was quantified for lipid peroxidation using arachidonic acid (AA) as agonist and 5-lipoxygenase (5-LOX) levels were determined using standard spectrometric assays. Further, molecular docking was performed by the ligand fit method using molegro software package (Molegro ApS, Aarhus, Denmark).

Results The study found that aqueous and ethanol extracts have very negligible effect (15%) with an IC₅₀ value of 13.8?mg/mL on PLA₂ from Naja naja venom. Further, extracts of WS also had very little effect (18%) with an IC₅₀ value of 16.6?mg/mL on malondialdehyde (MDA) formation. However, a 65% inhibition of 5-LOX with an IC₅₀ value of 0.92?mg/mL was observed in 1:1 ethanol extracts. The same was evident from SAR model with the active ingredient withaferin A binding predominantly on Phe 77, Tyr 98, Arg 99, Asp 164, Leu 168, Ser 382, Arg 395, Tyr 396 and Tyr 614 with an atomic contact energy value of??128.96 compared to standard phenidone (?103.61). Thus, the current study validates the application of WS for inflammatory diseases.

Conclusion This study reveals the inhibitory potential of W. somnifera on inflammatory enzymes and platelet aggregation. Thus, WS can serve as a newer, safer and affordable medicine for inflammatory diseases.     

Neuroprotective effect of nimesulide, a preferential COX-2 inhibitor, against pentylenetetrazol (PTZ)-induced chemical kindling and associated biochemical parameters in mice

Brain cyclooxygenases (COX), the rate-limiting enzyme in prostaglandin synthesis, is rapidly and transiently induced by convulsions in hippocampal and cortical neurons. Previous studies have explored the protective effect of naproxen (non-selective COX-inhibitor) or rofecoxib (selective COX-2 inhibitor) against chemical kindling in mice. With this background, the present study was designed to explore the possible effect of nimesulide (a preferential COX-2 inhibitor) against pentylenetetrazol (PTZ)-induced kindling epilepsy in mice. To induce kindling, PTZ was injected in a subconvulsive dose (40 mg/kg, i.p.) every other day for 15 days. Nimesulide (2.5 or 5 mg/kg, p.o.) was administered each day 45 min before either PTZ or vehicle challenge. The intensity of kindling was assessed immediately after PTZ administration according to a prevalidated scoring scale. On 16th day i.e. 24 h after the last dose of PTZ, animals were sacrificed and various biochemical parameters were assessed in the whole brain. Compared with normal control group, PTZ-kindled mice had significantly higher levels of malondialdehyde, nitrite, myeloperoxidase but had lower levels of reduced glutathione in the whole brain homogenate. Chronic treatment with nimesulide (2.5 or 5 mg/kg, p.o.) for 15 days showed significant decrease in kindling score and could play a role in controlling the accompanying biochemical alterations due to PTZ. These results suggested that nimesulide, a preferential COX-2 inhibitor offered neuroprotection against PTZ-induced kindling in mice.     

Ipsilateral mid-third clavicle fracture with grade V acromioclavicular joint dislocation

We report the case of a 20-year-old man with an ipsilateral mid-third clavicle fracture with grade V acromioclavicular joint (ACJ) dislocation. The combination of these two injuries is rare. A literature search produced various treatment algorithms. In this case, the patient was successfully treated with a Bosworth screw.This work was carried out in the Department of Orthopaedics, William Harvey Hospital, Ashford, Kent, UK     

Lactoferrin Interaction with Actinobacillus actinomycetemcomitans

The interaction of lactoferrin with Actinobacillus actinomycetemcomitans was examined in a ¹²⁵I-labeled protein binding assay. The binding of human and bovine lactoferrins reached maximum within 1 h. Lactoferrin binding to the bacterium was pH-dependent and reversible. Scatchard analysis indicated the existence of two different types of binding sites on the bacterium, one with a high affinity constant k_α=8.8×10⁻⁷ M) and the other with a low one (k_α=1.8×10⁻⁶ M). Bacteria in the exponential phase of growth showed higher binding than cells in the stationary phase. Bacteria grown in medium containing serum and/or lysed erythrocytes bound lactoferrin to a lesser extent. Heat-inactivated serum, lysed erythrocytes and other proteins such as mucin and laminin inhibited lactoferrin binding to A. actinomycetemcomitans in a competitive binding assay. Sodium dodecyl sulfate polyacrylamidegel electrophoresis and Western blot analysis of the cell envelope as well as the outer membrane of A. actinomycetemcomitans revealed lactoferrin-reactive protein bands at 29 kDa and 16.5 kDa. The 29-kDa band displayed a heat-modifiable lactoferrin-reactive form with a molecular weight of 34 kDa. Neither proteinase K-treated cell envelope nor lipopolysaccharide of this bacterium showed reactivity with lactoferrin. These data suggests a specific interaction of lactoferrin with outer membrane proteins of A. actinomycetemcomitans .     

Management of thoraco-lumbar fractures

The immediate surgical goals in the treatment of thoraco-lumbar fractures are decompression of compromised neural structures and stabilization of the vertebral column. If more sophisticated instrumentation is available, e.g. A.O.-fixateur interne or instrument set according to Kluger, stable reposition and reformation of compressed vertebral bodies also becomes possible. The long-term goals are to prevent delayed onset of spinal deformity, pain, and further neurological deficit. Early operative stabilization also shortens hospitalization time and allows immediate ambulation, thus lessening pulmonary, vascular, urological, and psychological complications. The Department of Neurosurgery, Sher-I-Kashmir Institute of Medical Sciences, treated 75 cases of thoraco-lumbar fractures. Out of 75 cases 63 were operated upon: 32 cases by spinal fusion alone and 31 by a combined procedure of decompression and posterior spinal fusion with fibular graft. 52 showed evidence of recovery ranging from moderate to excellent in a follow-up of 2-3 years. Thus surgery resulted not only in giving a stable spine to patients but also good improvement of neurodeficits. Our experiences demonstrate that operative treatment of thoraco-lumbar fractures can give satisfactory results even in situations where sophisticated instrumentation is not available.     

Dynamics of saccadic adaptation: differences between athletes and nonathletes.

PURPOSE: The aim of the study was to delineate differences in saccadic adaptation characteristics between a population of racquet sports athletes and nonathletes. METHODS: Eye movements were recorded at 120 Hz using a video-based eye tracker (ELMAR 2020) in a sample of 27 athletes (varsity badminton and squash players) and 14 nonathletes (<3 hours/week participation in recreational sports). Responses to negative positional error and positive positional error were studied in two sessions on separate days. Negative positional errors were induced by displacing the stimuli backwards by 3 degrees from the initial target step (12 degrees). Likewise, positive positional errors were induced by displacing the stimuli forward by 3 degrees . Amplitude gains were calculated for trials before, during, and after the adaptation phase. The magnitude and the rate of change of saccadic adaptation were determined from the amplitude gains. Differences between the groups were compared using regression analysis. RESULTS: No significant differences were found between the two groups in the magnitude of saccadic adaptation, both for negative (athletes -60%, nonathletes -57%) and positive (athletes +26%, and nonathletes +27%) positional error. Racquet sports athletes showed a significantly faster rate of adaptation for the positive positional error. A significant difference was not observed in the rate of adaptation for the negative positional error. CONCLUSIONS: Racquet sports athletes and nonathletes adapt to positional error signals by similar amounts. However, racquet sports athletes respond to positive positional errors at a faster rate, suggesting that a strategic component or environmental influences (such as practice) may play a role in saccadic adaptation.     

Unilateral proptosis secondary to diffuse condensing osteomyelitis

Osteomyelitis of the skull is an uncommon disease in the present days, mainly due to the advent of modern and more effective antibiotics. Hematogenous osteomyelitis is very rare. Osteomyelitis of the skull is usually not associated with sclerosis which is commonly seen in the rest of the skeleton. There are only few occasional case reports of condensing osteomyelitis wherein there was sclerosis of the bone associated with osteomyelitis of the skull and epidural abscess. An unusual case of diffuse condensing osteomyelitis of the skull producing unilateral proptosis is reported. The clinical, radiological features and microbiological aspects are presented. The proptosis was treated by excision of the bone behind the eyeball and thus relieving the proptosis and the impaired vision. The patient was given broad spectrum antibiotics for a period of two months. Further management problems are discussed.