Bioequivalence of a new coated 15 mg primaquine formulation for malaria elimination.

BACKGROUND: With only one 15 mg primaquine tablet registered by a stringent regulatory authority and marketed, more quality-assured primaquine is needed to meet the demands of malaria elimination. METHODS: A classic, two sequence, crossover study, with a 10-day wash out period, of 15 mg of IPCA-produced test primaquine tablets and 15 mg of Sanofi reference primaquine tablets was conducted. Healthy volunteers, aged 18-45 years, without glucose-6-phosphate dehydrogenase deficiency, a baseline haemoglobin ≥ 11 g/dL, creatinine clearance ≥ 70 mL/min/1.73 ms, and body mass index of 18.5-30 kg/m2 were randomized to either test or reference primaquine, administered on an empty stomach with 240 mL of water. Plasma primaquine and carboxyprimaquine concentrations were measured at baseline, then 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.333, 2.667, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0, 48.0 and 72.0 h by liquid chromatography coupled to tandem mass spectrometry. Primaquine pharmacokinetic profiles were evaluated by non-compartmental analysis and bioequivalence concluded if the 90% confidence intervals (CI) of geometric mean (GM) ratios of test vs. reference formulation for the peak concentrations (Cmax) and area under the drug concentration-time (AUC0-t) were within 80.00 to 125.00%. RESULTS: 47 of 50 volunteers, median age 33 years, completed both dosing rounds and were included in the bioequivalence analysis. For primaquine, GM Cmax values for test and reference formulations were 62.12 vs. 59.63 ng/mL, resulting in a GM ratio (90% CI) of 104.17% (96.92-111.96%); the corresponding GM AUC0-t values were 596.56 vs. 564.09 ngxh/mL, for a GM ratio of 105.76% (99.76-112.08%). Intra-subject coefficient of variation was 20.99% for Cmax and 16.83% for AUC0-t. Median clearances and volumes of distribution were similar between the test and reference products: 24.6 vs. 25.2 L/h, 189.4 vs. 191.0 L, whilst the median half-lives were the same, 5.2 h. CONCLUSION: IPCA primaquine was bioequivalent to the Sanofi primaquine. This opens the door to prequalification, registration in malaria endemic countries, and programmatic use for malaria elimination. Trial registration The trial registration reference is ISRCTN 54640699.

Recellularization of Acellular Xeno Kidney Scaffold: An In Vivo Method to Generate Bioartificial Kidney.

A significant hurdle for kidney tissue engineering is reproducing the complex three-dimensional structure of the kidney. In our study, a stepwise approach of generating a reproducible Xeno kidney scaffold from a goat kidney is described, which can be implanted and recellularized by host cells. We have proposed a combination of sodium dodecyl sulfate and Triton-X-100-based protocol to generate a reproducible Xeno kidney scaffold, which was then analyzed by histology, DNA quantification, SEM, and renal angiography. Further, a small portion from the cortico-medullar region of the acellular scaffold was implanted in the rat's kidney subcapsular pocket for a period of 1 month, to check the recruitment of host cells into the scaffold. Post implantation, the extracellular matrix of the scaffold was well preserved and it did not induce any damage or inflammation in the native kidney. Implantation of the Xeno scaffold resulted in apparent early vascularization which helped in the recruitment of the host cells, which was characterized by histology, immunohistochemistry, and scanning electron microscopy. Implanted Xeno scaffold showed AQP-1, Nephrin, α-SMA, and VEGF expression in proximal tubules and renal glomerulus. Importantly, Ki-67 and WTAP-expressing cells were also observed near proximal tubules suggesting a high level of proliferation in the scaffold. Thus, showing the potential of Xeno kidney development that can be recellularized by the host cell to engineer into a functional kidney.

Heparin coated decellularized xenogeneic small diameter vascular conduit for vascular repair with early luminal reendothelialization.

Small diameter vascular graft is a clinical need in cardiovascular disease (CAD) and peripheral atherosclerotic diseases (PAD). Autologous graft has limitations in availability and harvesting surgery. To make luminal surface modification with heparin coating in xenogeneic small diameter vascular graft. We constructed a conduit from decellularized human saphenous vein (HSV) matrices in small diameter vascular graft (< 0.8 mm diameter). Luminal surface modification was done with heparin coating for transplantation in the rat femoral artery. Biocompatibility of conduit was checked in Chorioallantoic Membrane (CAM) assay and in vivo. The blood flow rate in conduit grafts was measured, and immuno-histological analysis was performed. CAM assay and in vivo biocompatibility test showed cellular recruitment in the HSV scaffold. Heparin binding was achieved on the luminal surface. After three months of transplantation surgery neo-intimal layer was formed in the graft. The graft was patent for two weeks after surgery. There were no statistically differences between blood flow rate in graft (at proximal end 0.5 ± 0.01 m/s and at distal end 0.4 ± 0.01 m/s (n = 6)) and native artery (0.6 ± 0.1 m/second, (n = 3)). Biomarkers of endothelial cells, medial smooth muscle cells, and angiogenesis were observed in the transplanted graft. Our study demonstrates that xenogeneic decellularized vascular grafts with surface modification with heparin coating could be useful for the replacement of small diameter vessels.

Monitoring foot surface temperature using infrared thermal imaging for assessment of hoof health status in cattle: A review.

Detection of lameness early in cows is important from the animal welfare point of view and for reducing economic losses. Currently, many studies are being conducted for assessment of hoof health status by measuring the surface temperature of skin in cattle and other animal species in different parts of the world. Infrared Thermography (IRT) is able to detect lesions of hooves associated with lameness by measuring the changes in coronary band and hoof skin surface temperature. The surface temperature of a lame limb will be increased when the hoof has lesion(s). IRT has been used as a non-invasive diagnostic tool for early detection of hoof lesions based on the temperature difference between affected and non-affected hoof and maximum foot temperature on the regions of interest. In spite of having many potential applications in cattle production, factors affecting the temperature readings in thermograms must also are considered while taking images. Standard operating procedures must be established before taking thermographs under different circumstances, by considering all the factors that affect its normal function. IRT may help in minimising the cost of veterinary services, low yield, compromised fertility and culling expenses, where lameness cannot be resolved in early stages.

A comprehensive analysis of the emerging modern trends in research on photovoltaic systems and desalination in the era of artificial intelligence and machine learning.

Integration of photovoltaic (PV) systems, desalination technologies, and Artificial Intelligence (AI) combined with Machine Learning (ML) has introduced a new era of remarkable research and innovation. This review article thoroughly examines the recent advancements in the field, focusing on the interplay between PV systems and water desalination within the framework of AI and ML applications, along with it analyses current research to identify significant patterns, obstacles, and prospects in this interdisciplinary field. Furthermore, review examines the incorporation of AI and ML methods in improving the performance of PV systems. This includes raising their efficiency, implementing predictive maintenance strategies, and enabling real-time monitoring. It also explores the transformative influence of intelligent algorithms on desalination techniques, specifically addressing concerns pertaining to energy usage, scalability, and environmental sustainability. This article provides a thorough analysis of the current literature, identifying areas where research is lacking and suggesting potential future avenues for investigation. These advancements have resulted in increased efficiency, decreased expenses, and improved sustainability of PV system. By utilizing artificial intelligence technologies, freshwater productivity can increase by 10 % and efficiency. This review offers significant and informative perspectives for researchers, engineers, and policymakers involved in renewable energy and water technology. It sheds light on the latest advancements in photovoltaic systems and desalination, which are facilitated by AI and ML. The review aims to guide towards a more sustainable and technologically advanced future.

In vitro propagation and production of cardiotonic glycosides in shoot cultures of Digitalis purpurea L. by elicitation and precursor feeding.

Digitalis purpurea L. (Scrophulariaceae; Foxglove) is a source of cardiotonic glycosides such as digitoxin and digoxin which are commercially applied in the treatment to strengthen cardiac diffusion and to regulate heart rhythm. This investigation deals with in vitro propagation and elicited production of cardiotonic glycosides digitoxin and digoxin in shoot cultures of D. purpurea L. In vitro germinated seedlings were used as a primary source of explants. Multiple shoot formation was achieved for three explant types (nodal, internodal, and leaf) cultured on Murashige and Skoog (MS) medium with several treatments of cytokinins (6-benzyladenine-BA; kinetin-Kin; and thidiazuron-TDZ) and auxins (indole-3-acetic acid-IAA; α-naphthaleneacetic acid-NAA; and 2,4-dichlorophenoxy acetic acid-2,4-D). Maximum multiple shoots (12.7 ± 0.6) were produced from nodal explants on MS + 7.5 µM BA. Shoots were rooted in vitro on MS containing 15 µM IAA. Rooted plantlets were successfully acclimatized. To further maintain the multiple shoot induction, mother tissue was cut into four equal parts and repeatedly sub-cultured on fresh shoot induction liquid medium after each harvest. On adaptation of this strategy, an average of 18 shoots per explant could be produced. This strategy was applied for the production of biomass and glycosides digitoxin and digoxin in shoot cultures on MS medium supplemented with 7.5 µM BA and several treatments with plant growth regulators, incubation period, abiotic (salicylic acid, mannitol, sorbitol, PEG-6000, NaCl, and KCl), biotic (Aspergillus niger, Helminthosporium sp., Alternaria sp., chitin, and yeast extract) elicitors, and precursors (progesterone, cholesterol, and squalene). The treatment of KCl, mycelial mass of Helminthosporium sp., and progesterone were highly effective for the production of cardenolides. In the presence of progesterone (200 to 300 mg/l), digitoxin and digoxin accumulation was enhanced by 9.1- and 11.9-folds respectively.

MyrliMax® and Low Back Pain: A Multicentric, Observational, Post-Marketing Surveillance Study in Indian Patients Suffering from Chronic Low Back Pain of Various Pain Intensity.

Background: Chronic low back pain (LBP) is the most common musculoskeletal condition affecting a person's quality of life. Over the past decades, a lot of work was done in an attempt to reduce the negative impact of LBP, and help patients recover and maintain a better quality of life. Nevertheless, there is still a lot to be done to fully understand the problem of underlying chronic LBP and a wide gap that exist between basic science and applied rehabilitation research on LBP. Objectives: This was an open label, multicentric, observational, post-marketing surveillance study in a real-world setup designed to evaluate the efficacy and safety of MyrliMax® capsules containing standardised Commiphora myrrha gum resin extract in Indian subjects with chronic LBP varying in intensity. Materials and methods:This study included 204 subjects diagnosed with chronic LBP at the outpatient department of 20 centres under the supervision of a medical doctor. All subjects took MyrliMax® capsules twice daily for 20 days. Visual Analogue Scale (VAS) pain score, rescue medicine requirement, therapy satisfaction scores and safety parameters were assessed as per the schedule. Outcomes:Treatment with MyrliMax® capsules significantly (p<0.01) and progressively reduced the VAS score throughout treatment. A significant pain reduction was observed from the second visit. The mean VAS score was 6.58, 4.66, 2.99 and 1.88 on Day 0, Day 7, Day 14 and Day 20, respectively. A similar trend was also observed in subgroups based on gender and severity score. The need of rescue analgesics/NSAIDs was significantly reduced from the second week, indicating a potential of MyrliMax® capsules to increase the pain threshold. All physicians and patients were satisfied with the efficacy of MyrliMax® capsules assessed by physician's satisfaction score and patient's satisfaction score. There were no significant serious adverse events due to treatment during the study, which indicated that the treatment with MyrliMax® was well tolerated by subjects. Conclusion:MyrliMax® capsule is a potentially effective and safe therapy for pain reduction in patients suffering from chronic LBP. MyrliMax® capsules can be used to reduce pain in NSAIDs intolerant subjects suffering from chronic LBP.

Amelogenin Gene - The Pioneer in Gender Determination from Forensic Dental Samples.

INTRODUCTION: In the event of any mass fatality incident, DNA analysis plays a vital role in disaster victim identification. Teeth are one of the most resistant structures in the human body that resist decomposition hence making them prime choice for extracting DNA for identification of individuals. Polymerase Chain Reaction (PCR) analysis that target regions of Amelogenin gene have become the method of choice for sex determination of biological samples. AIM: Determining the sex of a given DNA sample from either dental pulp or dentin of tooth and help in identification of missing persons and disaster victims. MATERIALS AND METHODS: In our study 50 teeth samples were studied and they were subjected to various environmental conditions along with freshly extracted teeth taken as control for duration of one month and three months. Pulpal tissue was retrieved from the teeth specimens by access opening of root canals and for incinerated samples, the specimens were crushed. From the DNA that was extracted from the dental pulp sample Amelogenin gene locus was used for sex determination by amplifying a segment of X-Y homologous gene locus through PCR analysis. RESULTS: ANOVA test and t-test proved to be statistically significant and 100% retrieval rate was observed in samples. CONCLUSION: Pulpal tissue along with degenerating odontoblastic processes yield sufficient amount of DNA for gender determination when subjected to various forensic conditions with maximum accuracy.

Diagnostic role of 64-slice multidetector row CT scan and CT venogram in cases of cerebral venous thrombosis.

Retrospective review of patients with cerebral venous thrombosis (CVT) detected by 64-slice multidetector row computed tomography (MDCT). To evaluate the role of CT scan as the primary modality of imaging in suspected cases of CVT. Between October 2006 and September 2007, 53 patients, suspected to have CVT, underwent CT scan of the brain. Out of these, 33 patients were included in the study, who underwent non-contrast CT (NCCT), CT venous angiogram (MDCTA) and magnetic resonance venogram. Two blinded readers evaluated the NCCT and MDCTA. Final diagnosis was obtained after consensus reading of all the imaging by the two readers. Out of the total 33 patients, 20 patients were detected to have thrombosis of one or more of the cerebral venous sinuses or veins, at the concluding consensus reading. MDCTA together with NCCT could identify thrombosis in all of the 20 patients, i.e., 100% sensitivity and specificity. Sixty-four-slice MDCTA together with NCCT provided 100% sensitivity and specificity for the identification of CVT. It can be considered as a cost-effective and widely available, primary imaging modality in emergency situations.