Chemotaxonomic Studies on Centella asiatica (L.) Urb. from Varied Phytogeographical Conditions of India for Its Industrial Prospection

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Centella asiatica (L.) Urb. (Apiaceae) with high commercial value is an important herb in traditional Indian...     

Ratchet-traction effect: An underdiagnosed mechanism of pacing lead dislodgement

Pacing lead dislodgement contributes substantially, to the list of causes of early pacemaker failure.Reel''s syndrome is a rare cause of pacemaker failure, resulting from the dislodging of pacing electrodes by manipulation of the pulse generator by the patient. We describe here an intriguing case of pacemaker lead dislodgement by a novel and frequently underdiagnosed mechanism that mimicked the fluoroscopic diagnosis of reel''s syndrome.     

Novel Central Nervous System Drug Delivery Systems

For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood–brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood–brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection‐enhanced infusion, and ultrasound‐mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases.     

Hypolipidaemic Effect of Fenugreek Seeds: a Chronic Study in Non-insulin Dependent Diabetic Patients

The lipid lowering activity of fenugreek seeds ( Trigonella foenum graecum L.) was studied in 60 non-insulin dependent diabetic subjects. Isocaloric diets without and with fenugreek were given for 7 days and 24 weeks respectively. Ingestion of an experimental diet containing 25 g fenugreek seed powder resulted in a significant reduction of total cholesterol, LDL and VLDL cholesterol and triglyceride levels. These results indicate the beneficial effect of fenugreek seeds in diabetic subjects.     

How Important is the Tunnel Position in Outcomes Post-ACL Reconstruction: A 3D CT-Based Study

BackgroundDrilling the femoral and tibial tunnels at their anatomical locations are critical for good outcomes and involve seeing the footprints well. We intended to compare two techniques of drilling the tunnels and the patient-reported outcomes and knee stability of patients undergoing single bundle ACL reconstruction using 3D CT to evaluate if the tunnels were anatomical or not.Materials and MethodsSixty single bundle ACL reconstructions were analyzed, 30 each with Technique A and B. Pre-operative and after a minimum 27 month follow-up Lysholm, IKDC, Tegner score, hop test, and Lachman test were noted. 3D CT was done to classify femoral tunnels positions as being well placed, slightly or grossly misplaced and tibial tunnels as optimal or suboptimal and compared.ResultsSixty ACL reconstructions had full follow-up with a mean follow-up of 34 months. There was no significant difference between tunnel positions between the two techniques. Well-placed femoral tunnel had better Lysholm score (62.2 ± 16.2 v/s 48.5 ± 17.2, p 0.002) and IKDC score (62.5 ± 14.3 v/s 52.7 ± 15.1, p 0.012).). Those who had their surgeries within 3 months of their injury had better hop test (4.4 ± 0.9 v/s 3.9 ± 1, p 0.034) and IKDC scores (62.5 ± 15.8 v/s 33.2 ± 13.8, p 0.026) as compared to those that had surgery done after 3 monthsConclusionTibial tunnel positions were optimal in most cases and did not differ between the two techniques. Well-placed femoral tunnels and surgeries done within 3 months of the injury produced best results.     

Supracardiac Total Anomalous Pulmonary Venous Connection with A Descending Vertical Vein

The commonly used Darling classification for total anomalous pulmonary venous connection (TAPVC) consists of supracardiac, cardiac, infracardiac, and mixed types (Craig et al., Lab Invest 6:44–64, 1967). In supracardiac TAPVC, the common pulmonary vein drains superiorly into the left innominate vein, the superior vena cava, or the azygos vein by way of an ascending vertical vein. We describe a case of supracardiac TAPVC draining into the azygos vein atypically by way of a descending vertical vein.     

Divalent metal transporter 1 (DMT1) regulation by Ndfip1 prevents metal toxicity in human neurons

The regulation of metal ion transport within neurons is critical for normal brain function. Of particular importance is the regulation of redox metals such as iron (Fe), where excess levels can contribute to oxidative stress and protein aggregation, leading to neuronal death. The divalent metal transporter 1 (DMT1) plays a central role in the regulation of Fe as well as other metals; hence, failure of DMT1 regulation is linked to human brain pathology. However, it remains unclear how DMT1 is regulated in the brain. Here, we show that DMT1 is regulated by Ndfip1 (Nedd4 family-interacting protein 1), an adaptor protein that recruits E3 ligases to ubiquitinate target proteins. Using human neurons we show the Ndfip1 is upregulated and binds to DMT1 in response to Fe and cobalt (Co) exposure. This interaction results in the ubiquitination and degradation of DMT1, resulting in reduced metal entry. Induction of Ndfip1 expression protects neurons from metal toxicity, and removal of Ndfip1 by shRNAi results in hypersensitivity to metals. We identify Nedd4–2 as an E3 ligase recruited by Ndfip1 for the ubiquitination of DMT1 within human neurons. Comparison of brains from Ndfip1^−/− with Ndfip1^+/+ mice exposed to Fe reveals that Ndfip1^−/− brains accumulate Fe within neurons. Together, this evidence suggests a critical role for Ndfip1 in regulating metal transport in human neurons.