Impact of Shirodhara on biological markers of stress: A case study.

The unforgiving pace and complexity of modern life has greatly challenged our ability to live healthier and fully in the present moment. Industrialization, globalization, and competition in each sector lead to emotional stress and strain in life which is dangerous at the physical and mental levels. As per the classics of Ayurveda, chinta (stress) and atichintan (overthinking) are the causes of Rasavaha srotodushti which lead to many diseases. Shirodhara is an important healing technique of Ayurveda that has neuro-immuno-physio-psychological effects on the human body. Several studies have been carried out to evaluate the efficacy of Shirodhara in many diseases. A 35-yearold female patient with sleep deprivation, loss of concentration, and irritable mood symptoms was admitted to the hospital. She was assessed on the basis of the Profile Of Mood Score (POMS) questionnaire, Serum Cortisol (Sr. Cortisol), Dehydroepiandrosterone (DHEA). The patient was treated by Shirodhara with sesame oil for 14 days continuously. Results were assessed by biomarkers of stress and by POMS score. At the end of Shiroadhara, there was significant improvement found in presenting complaints as well as on the POMS Score and Stress biomarkers. During or after the treatment, no adverse events were observed.

Prakriti Analysis of COVID 19 Patients: An Observational Study.

RATIONALE & OBJECTIVE: The concept of Prakriti is unique to Ayurveda, which is used for deciding the preventive and curative strategy to be adopted in the treatment of patients. It is the total of anatomical, physiological, and psychological domains of an individual. The diseases often manifest by susceptibility that depends upon Prakriti of individuals. COVID 19 is a new disease, where the status of the susceptibility of its victim in terms of Prakriti is not known. This study has been undertaken to determine the Prakriti of COVID 19 positive patients. METHOD: The validated instrument CCRAS Prakriti assessment scale has been applied to the COVID 19 positive patients admitted between 16 May 2020 to 10 June 2020 at COVID hospital. RESULT: Data of 117 patients aged 10 to 80 years have been analyzed. The ratio of male-female patients was 1.8:1. Most patients belonged to Vata-KaphaPrakriti (27%).Individuals with their Prakriti found in order of frequency were Pitta-Kapha (21%), Kapha (20%), Vata (13%), Vata-Pitta (11%), Sama (4%) and Pitta (3%). CONCLUSION: Patients with Vata-Kapha, Pitta-Kapha, and Kapha dominant Prakriti have been found more in COVID19. The treatment strategies can be accordingly decided in respect of each patient.

Poly(ethylene glycol) (PEG)-lactic acid nanocarrier-based degradable hydrogels for restoring the vaginal microenvironment.

Women with bacterial vaginosis (BV) display reduced vaginal acidity, which make them susceptible to associated infections such as HIV. In the current study, poly(ethylene glycol) (PEG) nanocarrier-based degradable hydrogels were developed for the controlled release of lactic acid in the vagina of BV-infected women. PEG-lactic acid (PEG-LA) nanocarriers were prepared by covalently attaching lactic acid to 8-arm PEG-SH via cleavable thioester bonds. PEG-LA nanocarriers with 4 copies of lactic acid per molecule provided controlled release of lactic acid with a maximum release of 23% and 47% bound lactic acid in phosphate buffered saline (PBS, pH7.4) and acetate buffer (AB, pH4.3), respectively. The PEG nanocarrier-based hydrogels were formed by cross-linking the PEG-LA nanocarriers with 4-arm PEG-NHS via degradable thioester bonds. The nanocarrier-based hydrogels formed within 20 min under ambient conditions and exhibited an elastic modulus that was 100-fold higher than the viscous modulus. The nanocarrier-based degradable hydrogels provided controlled release of lactic acid for several hours; however, a maximum release of only 10%-14% bound lactic acid was observed possibly due to steric hindrance of the polymer chains in the cross-linked hydrogel. In contrast, hydrogels with passively entrapped lactic acid showed burst release with complete release within 30 min. Lactic acid showed antimicrobial activity against the primary BV pathogen Gardnerella vaginalis with a minimum inhibitory concentration (MIC) of 3.6 mg/ml. In addition, the hydrogels with passively entrapped lactic acid showed retained antimicrobial activity with complete inhibition G. vaginalis growth within 48 h. The results of the current study collectively demonstrate the potential of PEG nanocarrier-based hydrogels for vaginal administration of lactic acid for preventing and treating BV.

Polyethylene glycol-based hydrogels for controlled release of the antimicrobial subtilosin for prophylaxis of bacterial vaginosis.

Current treatment options for bacterial vaginosis (BV) have been shown to be inadequate at preventing recurrence and do not provide protection against associated infections, such as that with HIV. This study examines the feasibility of incorporating the antimicrobial peptide subtilosin within covalently cross-linked polyethylene glycol (PEG)-based hydrogels for vaginal administration. The PEG-based hydrogels (4% and 6% [wt/vol]) provided a two-phase release of subtilosin, with an initial rapid release rate of 4.0 µg/h (0 to 12 h) followed by a slow, sustained release rate of 0.26 µg/h (12 to 120 h). The subtilosin-containing hydrogels inhibited the growth of the major BV-associated pathogen Gardnerella vaginalis with a reduction of 8 log10 CFU/ml with hydrogels containing ≥15 µg entrapped subtilosin. In addition, the growth of four common species of vaginal lactobacilli was not significantly inhibited in the presence of the subtilosin-containing hydrogels. The above findings demonstrate the potential application of vaginal subtilosin-containing hydrogels for prophylaxis of BV.

Enhanced passive pulmonary targeting and retention of PEGylated rigid microparticles in rats.

The current study examines the passive pulmonary targeting efficacy and retention of 6µm polystyrene (PS) microparticles (MPs) covalently modified with different surface groups [amine (A-), carboxyl (C-) and sulfate (S-)] or single (PEG(1)-) and double (PEG(2)-) layers of α,ω-diamino poly(ethylene glycol) attached to C-MPs. The ζ-potential of A-MPs (-44.0mV), C-MPs (-54.3mV) and S-MPs (-49.6mV) in deionized water were similar; however PEGylation increased the ζ-potential for both PEG(1)-MPs (-18.3mV) and PEG(2)-MPs (11.5mV). The biodistribution and retention of intravenously administered MPs to male Sprague-Dawley rats was determined in homogenized tissue by fluorescence spectrophotometry. PEG(1)-MPs and PEG(2)-MPs demonstrated enhanced pulmonary retention in rats at 48h after injection when compared to unmodified A-MPs (59.6%, 35.9% and 17.0% of the administered dose, respectively). While unmodified MPs did not significantly differ in lung retention, PEGylation of MPs unexpectedly improved passive lung targeting and retention by modifying surface properties including charge and hydrophobicity but not size.

Pulmonary targeting microparticulate camptothecin delivery system: anticancer evaluation in a rat orthotopic lung cancer model.

Large (>6 microm) rigid microparticles (MPs) become passively entrapped within the lungs after intravenous (i.v.) injection making them an attractive and highly efficient alternative to inhalation for pulmonary delivery. In this study, PEGylated 6 microm polystyrene MPs with multiple copies of the norvaline (Nva) alpha-amino acid prodrug of camptothecin (CPT) were prepared. Surface morphology was characterized using a scanning electron microscope. CPT was released from the CPT-Nva-MPs over 24 h in rat plasma at 37 degrees C. In-vivo CPT plasma concentrations were low (approximately 1 ng/ml or less) and constant over a period of 4 days after a single i.v. injection of CPT-Nva-MPs as compared with high but short-lived systemic exposures after an i.v. injection of free CPT. This suggests that sustained local CPT concentrations were achieved in the lung after administration of the MP delivery system. Anticancer efficacy was evaluated in an orthotopic lung cancer animal model and compared with a bolus injection of CPT. Animals receiving free CPT (2 mg/kg) and CPT-Nva-MPs (0.22 mg/kg CPT and 100 mg/kg MPs) were found to have statistically significant smaller areas of lung cancer (P<0.05 and 0.01, respectively) than untreated animals. In addition, 40% of the animals receiving CPT-Nva-MPs were found to be free of cancer. The CPT dose using targeted MPs was 10 times lower than after i.v. injection of free CPT, but was more effective in reducing the amount of cancerous areas. In conclusion, CPT-Nva-MPs were able to achieve effective local lung and low systemic CPT concentrations at a dose that was 10 times lower than systemically administered CPT resulting in a significant improvement in anticancer efficacy in an orthotopic rat model of lung cancer.

Ligand-bound quantum dot probes for studying the molecular scale dynamics of receptor endocytic trafficking in live cells.

Endocytic receptor trafficking is a complex, dynamic process underlying fundamental cell function. An integrated understanding of endocytosis at the level of single or small numbers of ligand bound-receptor complexes inside live cells is currently hampered by technical limitations. Here, we develop and test ligand nerve growth factor-bound quantum dot (NGF-QD) bioconjugates for imaging discrete receptor endocytic events inside live NGF-responsive PC12 cells. Using single particle tracking, QD hybrid gel coimmunoprecipitation, and immuno-colocalization, we illustrate and validate the use of QD-receptor complexes for imaging receptor trafficking at synchronized time points after QD-ligand-receptor binding and internalization (t = 15-150 min). The unique value of these probes is illustrated by new dynamic observations: (1) that endocytosis proceeds at strikingly regulated fashion, and (2) that diffusive and active forms of transport inside cells are rapid and efficient. QDs are powerful intracellular probes that can provide biologists with new capabilities and fresh insight for studying endocytic receptor signaling events, in real time, and at the resolution of single or small numbers of receptors in live cells.

Quantum dots monitor TrkA receptor dynamics in the interior of neural PC12 cells.

Can quantum dots (QDs) serve as physiologically relevant receptor probes in the interior of cells? We directly visualize endocytosis, redistribution, and shuttling of QD bound-TrkA receptors to PC12 neural processes and far-reaching growth cone tips. Internalized QDs are contained in microtubule-associated vesicles and possess transport properties that reflect TrkA receptor dynamics. This opens up new possibilities for the development of QD platforms as molecular tools to image biochemical signaling and transport cargo in the cell interior.