Effect of Buteyko Breathing Technique as an Adjunct to Routine Physiotherapy on Pulmonary Functions in Patients Undergoing Off-pump Coronary Artery Bypass Surgery: A Randomized Controlled Trial.

Background: Coronary artery disease (CAD) poses a substantial and increasing public health concern in India, particularly among individuals aged 20 and above. The postoperative phase following coronary artery bypass graft (CABG) surgery presents potential complications, notably impacting the pulmonary system. Emerging evidence suggests that the Buteyko breathing technique not only improves lung function but also positively influences the psychological well-being of CABG patients. This study seeks to assess the impact of the Buteyko breathing technique on pulmonary functions in individuals who have undergone off-pump CABG. Materials and methods: In this randomized controlled trial, patients undergoing off-pump CABG were allocated to either the Buteyko breathing technique group (n = 35) or the control group (n = 35). The intervention group received supervised Buteyko breathing technique sessions twice daily for 15 minutes, concurrently with cardiac rehabilitation from postoperative day (POD-2 to POD-7). The control group underwent phase I cardiac rehabilitation. Outcome measures, including pulmonary function test (PFT), chest expansion, and breath-holding tests were evaluated at baseline (POD-2) and conclusion (POD-7). Results: Statistical analyses were conducted with a significance level set at p < 0.05. Both the control and intervention groups exhibited statistically significant improvements in pulmonary function, chest expansion at three levels, and breath-holding time (p = 0.0001). However, the Buteyko breathing group demonstrated a more significant improvement compared with the control group. Conclusion: The integration of the Buteyko breathing technique into conventional physiotherapy proves to be a beneficial strategy, leading to improvements in pulmonary function, breath-holding duration, and chest expansion for individuals who underwent off-pump CABG surgery. How to cite this article: Mavkar SS, Shukla MP. Effect of Buteyko Breathing Technique as an Adjunct to Routine Physiotherapy on Pulmonary Functions in Patients Undergoing Off-pump Coronary Artery Bypass Surgery: A Randomized Controlled Trial. Indian J Crit Care Med 2024;28(3):280-285.TRI Number: CTRI/2022/12/048295.

A study to evaluate the effectiveness of various disinfectants for extracted human teeth - A comparative study.

Objectives: The aim of this study was to evaluate the effectiveness of various disinfectants for extracting human teeth. The objectives were to assess the effectiveness of 5% vinegar, 3% hydrogen peroxide, 70% alcohol, and 5.25% sodium hypochlorite for disinfection of extracted human teeth. Methods: The teeth were divided into one of the following four groups consisting of 10 teeth in each group. All teeth were immersed in separate bottles containing 10 ml of the disinfectant for 7 days at 25°C. No visible growth in the broth was considered effective disinfection. The Institutional Ethics Committee (IEC) Number is SVIEC/ON/DENT/SRP/15186, and the IEC Clearance number is SVIEC/ON/DENT/SRP/15040. Results: Vinegar was most effective for bacterial disinfection, and 5.25% sodium hypochlorite was most effective for fungal disinfection. The result was statistically significant with Chi-square values of 0.015 and 0.057, respectively, and P < 0.001. Conclusions: Extracted teeth should be handled with extreme care as these are a potential source of infection. The present study documented the role of various disinfectants. Vinegar can be used as an effective disinfectant medium for extracting human teeth. Sterilisation and autoclaving are superior options while vinegar is cheap, readily available, and relatively non-toxic. All these qualities plus the fact that it has given encouraging results as an antibacterial disinfectant should necessitate its usage on a more regular basis than it is used at present.

The impact of a rub and rinse regimen on removal of human coronaviruses from contemporary contact lens materials.

PURPOSE: To assess the influence of contemporary contact lens (CL) materials on human coronavirus attachment and the influence of a rub and rinse step to remove these viruses. METHODS: The binding rates of HCoV-229E and HCoV-OC43 to eight soft CL materials and four rigid gas permeable materials were analyzed. The impact of a rub and rinse step to remove these viruses from all materials was examined. The efficacy of Biotrue (Bausch & Lomb), OPTI-FREE Puremoist (Alcon), Clear Care (Alcon) and cleadew (Ophtecs) to remove virus contamination from two representative soft lens materials (etafilcon A and lotrafilcon B) was also determined. RESULTS: Approximately 102 to 103 infectious viral particles were recovered from each CL material. Although some materials were more prone to coronavirus adhesion, contamination of both viral types was reduced to below the limit of quantification (LQ) from all materials using a simple saline rinse step. Exposure to Clear Care and cleadew reduced the number of infectious viral particles from both etafilcon A and lotrafilcon B to below the LQ, while for Biotrue and OPTI-FREE Puremoist, infectious viral particles were reduced to below the LQ only when additional rub and rinse steps were included. CONCLUSION: Human coronavirus contamination can be easily removed from CL surfaces. Although CL care products containing hydrogen peroxide and povidone-iodine efficiently removed virus contamination from CL surfaces without the need for a rub and rinse step, a full regimen including rub and rinse steps is crucial when using CL care products based on non-oxidative systems.

Antiviral Activity of Contemporary Contact Lens Care Solutions against Two Human Seasonal Coronavirus Strains.

Background: Given that reports have suggested SARS-CoV-2 can be transmitted via conjunctiva, the ability of contact lens (CL) care products to reduce the infectiousness of two seasonal human coronavirus (HCoV) (HCoV-229E and HCoV-OC43) surrogates for SARS-CoV-2 was investigated. Methods: Biotrue and Boston Simplus (Bausch&Lomb), OPTI-FREE Puremoist and Clear Care (Alcon), and cleadew and cleadew GP (Ophtecs) were tested. Their ability to inactivate HCoV was evaluated using contact times of 4 and 6 h as well as 1% and 10% of virus inoculum. Results: Non-oxidative systems (Biotrue, Boston Simplus, and OPTI-FREE) did not exhibit a significant log10 reduction compared to controls for the two viral strains for either incubation time (all p > 0.05) when 10% tests were performed. For the 1% test, while Boston Simplus and OPTI-FREE exhibited a significant log10 reduction of both HCoV-229E (after 6 h) and HCoV-OC43 (after either 4 or 6 h incubation), those products showed less than 1 log10 reduction of the two infectious viruses. Oxidative systems based on hydrogen peroxide or povidone-iodine showed a significant log10 reduction compared with the controls for both HCoV-229E and HCoV-OC43 in all tested conditions (all p < 0.01). Clear Care led to virus inactivation to below the limit of quantification for tests performed with 1% of inoculum after 6 h incubation, while cleadew and cleadew GP led to inactivation of the two viruses to below the limit of quantification in all tested conditions. Conclusion: Oxidative CL disinfection systems showed significant virucidal activity against HCoV-229E and HCoV-OC43, while non-oxidative systems showed minimal ability to inactivate the HCoV species examined.

CRISPR-based assays for rapid detection of SARS-CoV-2.

COVID-19 pandemic posed an unprecedented threat to global public health and economies. There is no effective treatment of the disease, hence, scaling up testing for rapid diagnosis of SARS-CoV-2 infected patients and quarantine them from healthy individuals is one the best strategies to curb the pandemic. Establishing globally accepted easy-to-access diagnostic tests is extremely important to understanding the epidemiology of the present pandemic. While nucleic acid based tests are considered to be more sensitive with respect to serological tests but present gold standard qRT-PCR-based assays possess limitations such as low sample throughput, requirement for sophisticated reagents and instrumentation. To overcome these shortcomings, recent efforts of incorporating LAMP-based isothermal detection, and minimizing the number of reagents required are on rise. CRISPR based novel techniques, when merge with isothermal and allied technologies, promises to provide sensitive and rapid detection of SARS-CoV-2 nucleic acids. Here, we discuss and present compilation of state-of-the-art detection techniques for COVID-19 using CRISPR technology which has tremendous potential to transform diagnostics and epidemiology.

Mesenchymal stem cells are prospective novel off-the-shelf wound management tools.

Chronic/non-healing cutaneous wounds pose a debilitating burden on patients and healthcare system. Presently, treatment modalities are rapidly shifting pace from conventional methods to advanced wound care involving cell-based therapies. Mesenchymal stem cells (MSCs) have come across as a prospective option due to its pleiotropic functions viz. non-immunogenicity, multipotency, multi-lineage plasticity and secretion of growth factors, cytokines, microRNAs (miRNA), exosomes, and microvesicles as part of their secretome for assisting wound healing. We outline the therapeutic role played by MSCs and its secretome in suppressing tissue inflammation, causing immunomodulation, aiding angiogenesis and assisting in scar-free wound healing. We further assess the mechanism of action by which MSCs contribute in manifesting tissue repair. The review flows ahead in exploring factors that influence healing behavior including effect of multiple donor sites, donor age and health status, tissue microenvironment, and in vitro expansion capability. Moving ahead, we overview the advancements achieved in extending the lifespan of cells upon implantation, influence of genetic modifications aimed at altering MSC cargo, and evaluating bioengineered matrix-assisted delivery methods toward faster healing in preclinical and clinical models. We also contribute toward highlighting the challenges faced in commercializing cell-based therapies as standard of care treatment regimens. Finally, we strongly advocate and highlight its application as a futuristic technology for revolutionizing tissue regeneration.

Association of VEGFA promoter polymorphisms rs699947 and rs35569394 with diabetic retinopathy among North-Central Indian subjects: a case-control study.

BACKGROUND: Diabetes mellitus type 2 is often described as the global pandemic of the 21st century with India emerging as its capital. Microvascular complications such as retinopathy associated with diabetes are a serious world health problem, leading to the already existing burden of blindness. The aim of this study was to determine whether VEGF gene polymorphisms rs35569394 and rs699947 are associated with DR in North Indians. MATERIALS AND METHODS: North Indian subjects, diabetic controls with no retinopathy (DR I, n = 51), subjects with diabetes with mild-moderate retinal changes (DR II, n = 50), and subjects with diabetes with severe retinopathy with/without retinal neovascularization (DR III, n = 55) were recruited for this study. Genotyping of the VEGF gene I/D polymorphism was done by PCR and C/A polymorphism by PCR-RFLP method. RESULTS: DD-genotype was 2.73 times over expressed among DR III category (p = .02; OR: 2.73; 95% CI: 1.20-6.19) as compared to DR I category among male subgroup. C-allele (rs699947) had 1.66-times more exposure among DR III as compared to DR I (C vs. A allele; p = .063; OR: 1.66; 95% CI: 0.97-2.84), probably due to high linkage disequilibrium between both the polymorphisms. CONCLUSIONS: Results of our study support the hypothesis that D-allele and DD-genotype of rs35569394 have deleterious effect on the progression of DR. C-allele had skewed frequency towards DR III subjects owing to strong linkage disequilibrium between C-allele (rs699947) and D-allele (rs35569394).

In vitro and in vivo evaluation of cyclosporine-graphene oxide laden hydrogel contact lenses.

Drug-eluting contact lens can substitute the multiple eye drop therapy. However, loading hydrophobic drug like cyclosporine in the contact lens is very challenging, due to low drug uptake (via soaking method); and alteration in the swelling and optical properties which restricts its clinical application. To address the above issues, graphene oxide (GO, large surface area with oxygen containing functional groups) was incorporated in the contact lenses during fabrication. These GO-laden contact lenses (SM-GO-Cys) as well as blank contact lenses (SM-Cys) were soaked in the solution of cyclosporine. Alternatively, cyclosporine-laden contact lenses (DL-Cys-20) and cyclosporine-GO-laden contact lenses (DL-Cys-20-GO) were fabricated by adding drug and drug-GO (at various level of GO) during fabrication, respectively. Contact angle and swelling data showed increase in water holding capacity of GO laden contact lenses. Optical property was significantly improved due to molecular dispersion of drug on the surface of GO sheets. The drug uptake and in vitro release profile was improved with GO-laden contact lenses by soaking method (SM-GO-Cys-400n) due to hydrophobic interactions between GO and drug. Adding cyclosporine-GO (DL-Cys-20-GO-800n) during fabrication significantly improved drug release kinetics with higher drug leaching (during extraction and sterilization) due to increased swelling, improved dissolution and molecular dispersion of drug on GO sheets. Ocular irritation and histopathological studies demonstrated the safety of GO-contact lens. The in vivo drug release studies in the rabbit eye showed significant improvement in mean residence time (MRT) and area under the curve (AUC) using DL-Cys-20-GO-800n contact lens compared to eye drop solution with reduction in protein adherence value. The study demonstrated that the incorporation of GO into the contact lens can control the release of cyclosporine as well as improved the lens swelling and transmittance properties.

Secretomics: a biochemical footprinting tool for developing microalgal cultivation strategies.

Microalgae offer a promising source of biofuel and a wide array of high-value biomolecules. Large-scale cultivation of microalgae at low density poses a significant challenge in terms of water management. High-density microalgae cultivation, however, can be challenging due to biochemical changes associated with growth dynamics. Therefore, there is a need for a biomarker that can predict the optimum density for high biomass cultivation. A locally isolated microalga Cyanobacterium aponinum CCC734 was grown with optimized nitrogen and phosphorus in the ratio of 12:1 for sustained high biomass productivity. To understand density-associated bottlenecks secretome dynamics were monitored at biomass densities from 0.6 ± 0.1 to 7 ± 0.1 g/L (2 to 22 OD) in batch mode. Liquid chromatography coupled with mass spectrometry identified 880 exometabolites in the supernatant of C. aponinum CCC734. The PCA analysis showed similarity between exometabolite profiles at low (4 and 8 OD) and mid (12 and 16 OD), whereas distinctly separate at high biomass concentrations (20 and 22 OD). Ten exometabolites were selected based on their role in influencing growth and are specifically present at low, mid, and high biomass concentrations. Taking cues from secretome dynamics, 5.0 ± 0.5 g/L biomass concentration (16 OD) was optimal for C. aponinum CCC734 cultivation. Further validation was performed with a semi-turbidostat mode of cultivation for 29 days with a volumetric productivity of 1.0 ± 0.2 g/L/day. The secretomes-based footprinting tool is the first comprehensive growth study of exometabolite at the molecular level at variable biomass densities. This tool may be utilized in analyzing and directing microalgal cultivation strategies and reduction in overall operating costs.

Controlled bimatoprost release from graphene oxide laden contact lenses: In vitro and in vivo studies.

Ocular drug delivery using contact lenses may be able to substitute for eye drop therapy. However, issues with hydrophobic drugs (like bimatoprost that is used to treat glaucoma) such as low drug uptake using a simple soaking method into preformed contact lenses and alteration in the swelling and transmittance of lenses restricts the application for drug delivery. This research uses graphene oxide (GO) to control the release of bimatoprost from contact lenses along with improvements in the drug uptake, and lens swelling and transmittance. GO was loaded into silicone hydrogel contact lenses by adding the GO at the same time as lenses were polymerized. These lenses were soaked in bimatoprost. Alternatively contact lenses, either with or without GO, were produced by adding bimatoprost during lens polymerization. GO improved contact lens swelling due to its water binding capacity and lens transmittance due to the molecular dispersion of bimatoprost on the surface of the GO which prevented the local precipitation of the drug. The bimatoprost uptake was not improved in the presence of GO. However, its in vitro release profile was improved. Adding bimatoprost and GO at the same time as lenses were polymerized (DL-GO-BMT) significantly decreased the loss of drug during extraction and sterilization in comparison to contact lenses (DL-BMT) without GO. As the amount of GO was increased, the DL-GO-BMT lenses showed a significant decrease in the burst and cumulative release of bimatoprost. Ocular irritation and histopathology reports demonstrated the safety of GO contact lens. The in vivo pharmacokinetic studies in the rabbit tear fluid showed significant improvement in mean residence time (MRT) and area under the curve (AUC) with DL-GO-0.2 µg-BMT-100 contact lens in comparison to eye drop solution. The study demonstrated that the addition of GO to contact lenses can control the release of bimatoprost as well as improved the lens swelling and transmittance. However, further optimization is needed to modulate the release of drug within the therapeutic level to manage glaucoma.

Optimization and validation of RT-LAMP assay for diagnosis of SARS-CoV2 including the globally dominant Delta variant.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 pandemic, has infected more than 179 million people worldwide. Testing of infected individuals is crucial for identification and isolation, thereby preventing further spread of the disease. Presently, Taqman™ Reverse Transcription Real Time PCR is considered gold standard, and is the most common technique used for molecular testing of COVID-19, though it requires sophisticated equipments, expertise and is also relatively expensive. OBJECTIVE: Development and optimization of an alternate molecular testing method for the diagnosis of COVID-19, through a two step Reverse Transcription Loop-mediated isothermal AMPlification (RT-LAMP). RESULTS: Primers for LAMP were carefully designed for discrimination from other closely related human pathogenic coronaviruses. Care was also taken that primer binding sites are present in conserved regions of SARS-CoV2. Our analysis shows that the primer binding sites are well conserved in all the variants of concern (VOC) and variants of interest (VOI), notified by World Health Organization (WHO). These lineages include B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.427/B.1.429, P.2, B.1.525, P.3, B.1.526 and B.1.617.1. Various DNA polymerases with strand displacement activity were evaluated and conditions were optimized for LAMP amplification and visualization. Different LAMP primer sets were also evaluated using synthetic templates as well as patient samples. CONCLUSION: In a double blind study, the RT-LAMP assay was validated on more than 150 patient samples at two different sites. The RT-LAMP assay appeared to be 89.2% accurate when compared to the Taqman™ rt-RT-PCR assay.

Development of an In Vitro Blink Model for Ophthalmic Drug Delivery.

PURPOSE: The purpose of this study was to develop an advanced in vitro blink model that can be used to examine the release of a wide variety of components (for example, topical ophthalmic drugs, comfort-inducing agents) from soft contact lenses. METHODS: The model was designed using computer-aided design software and printed using a stereolithography 3D printer. The eyelid and eyeball were synthesized from polyvinyl alcohol and silicone material, respectively. Simulated tear fluid was infused through tubing attached to the eyelid using a syringe pump. With each blink cycle, the eyelid slides and flexes across the eyeball to create an artificial tear film layer. The flow-through fluid was collected using a specialized trough. Two contact lenses, etafilcon A and senofilcon A, were incubated in 2 mL of a water-soluble red dye for 24 h and then placed on the eye model (n = 3). The release of the dye was measured over 24 h using a tear flow rate of 5 µL/min. RESULTS: Approximately 25% of the fluid that flowed over the eye model was lost due to evaporation, nonspecific absorption, and residual dead volume. Senofilcon A absorbed more dye (47.6 ± 2.7 µL) than etafilcon A (22.3 ± 2.0 µL). For etafilcon A, the release of the dye followed a burst-plateau profile in the vial but was sustained in the eye model. For senofilcon A, the release of the dye was sustained in both the vial and the eye model, though more dye was released in the vial (p < 0.05). Overall, the release of the dye from the contact lenses was higher in the vial compared with the eye model (p < 0.05). CONCLUSION: The blink model developed in this study could be used to measure the release of topical ophthalmic drugs or comfort agents from contact lenses. Simulation of a blink mechanism, an artificial tear film, and nonspecific absorption in an eye model may provide better results than a simple, static vial incubation model.

Advances and clinical challenges for translating nerve conduit technology from bench to bed side for peripheral nerve repair.

Injuries to the peripheral nervous system remain a large-scale clinical problem. These injuries often lead to loss of motor and/or sensory function that significantly affects patients' quality of life. The current neurosurgical approach for peripheral nerve repair involves autologous nerve transplantation, which often leads to clinical complications. The most pressing need is to increase the regenerative capacity of existing tubular constructs in the repair of large nerve gaps through development of tissue-engineered approaches that can surpass the performance of autografts. To fully realize the clinical potential of nerve conduit technology, there is a need to reconsider design strategies, biomaterial selection, fabrication techniques and the various potential modifications to optimize a conduit microenvironment that can best mimic the natural process of regeneration. In recent years, a significant progress has been made in the designing and functionality of bioengineered nerve conduits to bridge long peripheral nerve gaps in various animal models. However, translation of this work from lab to commercial scale has not been achieve. The current review summarizes recent advances in the development of tissue engineered nerve guidance conduits (NGCs) with regard to choice of material, novel fabrication methods, surface modifications and regenerative cues such as stem cells and growth factors to improve regeneration performance. Also, the current clinical potential and future perspectives to achieve therapeutic benefits of NGCs will be discussed in context of peripheral nerve regeneration.

VEGFA Promoter Polymorphisms rs699947 and rs35569394 Are Associated With the Risk of Anterior Cruciate Ligament Ruptures Among Indian Athletes: A Cross-sectional Study.

BACKGROUND: Associations of genetic variants within certain fibril-forming genes have previously been observed with anterior cruciate ligament (ACL) injuries. Evidence suggests a significant role of angiogenesis-associated cytokines in remodeling the ligament fibril matrix after mechanical loading and maintaining structural and functional integrity of the ligament. Functional polymorphisms within the vascular endothelial growth factor A (VEGFA) gene have emerged as plausible candidates owing to their role in the regulation of angiogenic responses. HYPOTHESIS: VEGFA promoter polymorphisms rs699947 and rs35569394 are associated with ACL injury risk among athletes. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A total of 90 Indian athletes with radiologically confirmed or surgically proven isolated ACL tears and 76 matched-control athletes were selected for the present cross-sectional genetic association study. Oral mouthwash samples were collected from all the case and control athletes and genotyped for VEGFA rs699947 and rs35569394 using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The A allele (rs699947) was significantly overrepresented in the ACL group (C vs A allele: odds ratio [OR], 1.68 [95% CI, 1.08-2.60]; P = .021) (CC vs CA + AA: OR, 2.69 [95% CI, 1.37-5.26]; P = .004). There was a greater frequency of the AA genotype in the ACL group in comparison with the control group (OR, 3.38 [95% CI, 1.23-9.28]; P = .016) when only male athletes were compared. Likewise, there was a greater frequency of the I allele (rs35569394) in the ACL group (D vs I allele: OR, 1.64 [95% CI, 1.06-2.55]; P = .025) (DD vs ID + II: OR, 2.61 [95% CI, 1.31-5.21]; P = .006). The A-I haplotype was overrepresented in the ACL group compared with the control group (OR, 1.68 [95% CI, 1.08-2.60]; χ2 = 5.320; P = .021), and both the polymorphisms were found to be in complete linkage disequilibrium (r 2 = 0.929; logarithm of the odds score = 63.74; D' = 1.0). Female athletes did not show any difference in genotype or allele frequency. CONCLUSION: This is the first study to investigate the association of VEGFA promoter polymorphisms in ACL tears among Indian athletes. Increased frequencies of the A allele (rs699947) and I allele (rs35569394) were observed in the ACL group. These results suggest that sequence variants in the VEGF gene are associated with ACL injury risk among athletes. Further research with long-term follow-ups measuring VEGF expression levels during recovery is warranted to establish its role in ACL injuries and healing.

Novel Poly(vinylpyrrolidone)-Coated Silicone Contact Lenses to Improve Tear Volume During Lens Wear: In Vitro and In Vivo Studies.

Poly(vinylpyrrolidone) (PVP-K90) is widely used to manage dry eye syndrome (DES). The marketed eye drop solutions (high dose) need frequent instillation, affecting the routine lifestyle of patients. PVP-K90-laden contact lenses can be used to overcome the limitations of eye drop solutions (low bioavailability and frequent instillation). However, the conventional methods of PVP-K90 loading show poor loading capacity and short duration of effect. In the present study, we have developed PVP-K90-coated contact lenses via a short curing approach to increase the PVP-K90 loading capacity with a sustained release profile to manage dry eye syndrome. PVP-K90 was loaded by a soaking method (SM-PVP), direct loading (during fabrication, DL-PVP), a combination of soaking and direct loading (DL-SM-PVP), and a novel coating process (SM-PVP-C and DL-SM-PVP-C). The swelling studies suggested improvement in the water uptake (hydration) property of the contact lenses due to the presence of PVP-K90. The optical transparency was within an acceptable range. The in vitro release of PVP-K90 was in the following order: PVP-coated contact lens (168 h) > DL-SM-PVP (168 h) > DL-PVP (96 h) > SM-PVP (72-96 h). PVP-coated contact lenses showed a high burst effect (lubricating effect) and sustained release (3161-448 ng/h between 24 and 168 h) due to high PVP loading/coating in comparison to the uncoated respective contact lenses (964-113 ng/h between 24 and 96 h). In animal studies, the PVP-K90-coated contact lens showed higher tear volume in comparison to the respective uncoated contact lenses and an eye drop solution. This study demonstrates a novel approach of coating a high amount of PVP-K90 on contact lenses for sustained release to manage several ocular diseases like dry eye syndrome, conjunctivitis, and other ocular injuries.

COLIA1 + 1245 G > T Sp1 Binding Site Polymorphism is Not Associated with ACL Injury Risks Among Indian Athletes.

OBJECTIVE: Type I collagen polypeptides contribute significantly to the structural composition of ligament tissue matrix. Since anterior cruciate ligament (ACL) tears account for roughly 50% of all knee injuries in sports, the objective of the study was to investigate association of Sp1-transcription factor binding site polymorphism COLIA1 Sp1 + 1245 G > T with ACL injury risk among Indian athletes. METHODS: A total of 166 athletes (90 with ACL tears and 76 as control) were recruited and were genotyped for COLIA1 Sp1 + 1245 G > T polymorphism using allele-specific PCR (AS-PCR) method. RESULT: Both the groups were matched for nature of sports, training regimen, and other demographic characteristics. We observed no significant difference between ACL cases and control group in GT or TT genotype frequency distribution (p = 0.967) and T-allele frequency distribution (p = 0.861) for COLIA1 Sp1 + 1245 G > T polymorphism. Also, the three models of inheritance of minor allele failed to show any statistical significance in the present study. CONCLUSION: COLIA1 Sp1 + 1245 G > T polymorphism has been studied in relation to many connective tissue pathologies. This is probably the first study to investigate the association of collagen protein genes with ACL injury risk on Indian athletes. Further studies with more SNPs in genes encoding fibril-forming collagen and large sample sizes are necessary to fully understand the genetic link to ACL injuries among athletes.

Multiple drug delivery from the drug-implants-laden silicone contact lens: Addressing the issue of burst drug release.

A fixed combination of bimatoprost/timolol eye drop solution is used to manage the elevated intra-ocular pressure in glaucoma patients, including individuals whose condition is poorly controlled by monotherapy. Eye drop solutions are generally given in high dose, due to poor ocular bioavailability. The high ocular dose of bimatoprost and timolol lead to hyperaemia and systemic cardiac side effects respectively. Here, we introduce multiple implant-laden contact lenses (IM) to passively deliver timolol, bimatoprost and hyaluronic acid at therapeutically relevant doses without high burst release. The drug-loaded implants were individually implanted in the outer periphery of the silicone contact lenses. Atomic force microscopy showed the smooth surface of the implant contact lens, as the implants were inside the contact lens matrix. The implant lens (IM) showed major loss of drugs [timolol = 60.60%, bimatoprost = 61.75% and HA = 46.03%] during the monomer extraction and wet sterilization, while the option of dry radiation sterilization (IM-R lens) and hydration for 24 h prior to use showed relatively lower loss of drugs [timolol = 16.87%, bimatoprost = 47.95% and HA = 24.41%]. The in-vitro drugs release data of IM-R lens, showed sustained release for 72 h, with low burst release in comparison to the soaked (SM) and direct drug-laden contact lenses (DL). The in vivo drug release data in the rabbit tear fluid showed sustained release using IM-R lens in comparison to the SM lens and eye drop therapy. The burst release with the IM-R lens was many folds reduced, which could bypass the side effects associated with multiple eye drop therapy. The in vivo pharmacodynamic study in the rabbit model showed peak and valley profile with multiple eye drop therapy, while IM-R lens showed prolong reduction in intra ocular pressure (IOP) for 120 h. The study demonstrates the application of implantation technology to deliver multiple drug through contact lenses to treat glaucoma.

Tailored gatifloxacin Pluronic® F-68-loaded contact lens: Addressing the issue of transmittance and swelling.

Loading of gatifloxacin in contact lenses affects critical lens properties (optical and swelling) owing to drug precipitation in the contact lens matrix. The presence of Pluronic® F-68 in the packaging solution creates in-situ micelles in the contact lens to dissolve gatifloxacin precipitates and provide sustained drug release. The micelles further improved the drug uptake from the drug-packaging solution to create an equilibrium of drug between the lens matrix and the packaging solution. In this study, we optimized gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and gatifloxacin loading capacity as well as sustained drug delivery. Optimization of gatifloxacin-pluronic-loaded contact lens was carried out using a 32 factorial design by tailoring the concentration of Pluronic® F-68 in the packaging solution (X1) and the amount of gatifloxacin in the monomer solution (X2) to achieve the desired lens properties. The optimized batch (X1 = 0.3%w/v and X2 = 0.3%w/v) showed an optical transmittance of 92.84%, swelling of 92.36% and gatifloxacin loading capacity of 92.56 µg. The in vitro flux data of the optimized batch (GT-Pl-CL) showed sustained release up to 72 h, whereas soaked contact lenses (SM-CL) and direct gatifloxacin-loaded contact lenses (DL-CL) showed a sustained release up to 48 h. The in vivo gatifloxacin release data for rabbit tear fluid showed sustained release with a high gatifloxacin level for the GT-Pl-CL lens in comparison to the SM-CL and the eye drop solution. This study demonstrates the application of the 32 full factorial design to optimize gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and drug loading capacity.

Moderate noise associated oxidative stress with concomitant memory impairment, neuro-inflammation and neurodegeneration.

Noise, a disturbing and unwanted sound is currently being perceived as a widespread environmental stressor. In the present study we investigated the activation of oxidative stress as a mechanism involved in cognitive impairment through changes in neuro-inflammation. Sprague Dawley rats (200-220 â€‹ â€‹g â€‹m) were exposed to moderate (100dB) sound pressure level (SPL) noise daily for 2 â€‹h â€‹s over a period of 15 and 30 days and the consequence on brain regions of hippocampus observed through behavioral studies by Morris Water Maze to assess effects on spatial memory coupled with biochemical evaluation of markers of oxidative stress and inflammation. Further, the underlying mechanism pertaining to apoptosis was investigated by immuno-histological studies through assessment of Caspase-3 and TUNEL assay as well as morphological parameters, namely Nissl bodies in CA1, CA3 and DG regions of hippocampus. Poorer performance in the MWM indicative of decrement in concept formation, attention, working memory, and reference memory was observed on 15 and 30 days of noise exposures. At the cellular level, increased oxidative stress and inflammation was noticed as evinced by elevated levels of TNF-α, IL-6, IL-1α and IFN-γ in both hippocampus and plasma. Exposure to noise also led to a gradual increase in the number of pyknotic and apoptotic neurons together with the increase in DNA fragmentation in hippocampus. Increased levels of inflammatory genes (i.g.) ccl2, ccr5, ifng, il13, il1a, tnfa coupled with decreased levels of bmp2 and il3 genes were found in both the noise exposure groups. Our findings revealed that moderate intensity noise exposure impaired early memory changes in expression of several gene families including genes associated with regulation of transcription, inflammatory response, and, response to oxidative stress.

Cyclosporine laden tailored microemulsion-gel depot for effective treatment of psoriasis: In vitro and in vivo studies.

Psoriasis is a widespread chronic disease affecting 1-3 % of total population. In major cases (>80 %), it is treated by topical application of corticosteroids. However, the topical route is very challenging due to physico-chemical nature of diseased stratum corneum and so no single treatment works for every patient. The oral route showed severe side effects due to systemic immunosuppression, which can be avoided by topical route. The aim of the research work was to investigate cyclosporine loaded microemulsion based gel for effective cyclosporine permeation and retention in the skin tissue for psoriasis treatment. The pseudo ternary phase diagram at three Smix ratios (2:1, 1:1, and 1:2; Tween 80: isopropyl alcohol) were constructed using isopropyl myristate as oil phase. The Smix at 2:1 ratio showed large microemulsion area. The transmission electron microscope images showed spherical non-aggregated oil globules with the size < 50 nm. The selected microemulsion (Cy-2-ME12O55SM) was incorporated in Carbopol 940 gel for topical application. The ex vivo diffusion study showed improved permeation (>24 h) with microemulsion-gel in comparison to cyclosporine suspension. The microemulsion-gel was non-irritating on the rabbit skin. In drug retention studies, microemulsion-gel showed high drug retention (trapping, 38.92 %) in the skin tissue, which was due to destabilization of microemulsion after penetration in the skin layer causing precipitation of cyclosporine. The depot effect due to cyclosporine precipitates could be helpful for sustained effect of cyclosporine for the effective treatment of psoriasis.