Antibacterial, Remineralising and Matrix Metalloproteinase Inhibiting Scandium-doped Phosphate Glasses for Treatment of Dental Caries

Objectives: Antibiotic resistance is increasingly a growing global threat. This study aimed to investigate the potential use of newly developed scandium-doped phosphate-based glasses (Sc-PBGs) as an antibacterial and anticariogenic agent through controlled release of Sc3+ ions. Methods: Sc-PBGs with various calcium and sodium oxide contents were produced and characterised using thermal and spectroscopic analysis. Degradation behaviour, ion release, antibacterial action against Streptococcus mutans, anti-matrix metalloproteinase-2 (MMP-2) activity, remineralisation potential and in vivo biocompatibility were also investigated. Results: The developed glass system showed linear Sc3+ ions release over time. The released Sc3+ shows statistically significant inhibition of S. mutans biofilm (1.2 log10 CFU reduction at 6 h) and matrix metalloproteinase-2 (MMP-2) activity, compared with Sc-free glass and positive control. When Sc-PBGs were mounted alongside enamel sections, subjected to acidic challenges, alternating hyper- and hypomineralisation layers consistent with periods of re- and demineralisation were observed demonstrating their potential remineralising action. Furthermore, Sc-PBGs produced a non-toxic response when implanted subcutaneously for 2 weeks in Sprague Dawley rats. Significance: Since Sc3+ ions might act on various enzymes essential to the biological mechanisms underlying caries, Sc-PBGs could be a promising therapeutic agent against cariogenic bacteria

Novel lactoferrin-conjugated gallium complex to treat Pseudomonas aeruginosa wound infection

Pseudomonas aeruginosa is one of the leading causes of opportunistic infections such as chronic wound infection that could lead to multiple organ failure and death. Gallium (Ga3+) ions are known to inhibit P. aeruginosa growth and biofilm formation but require carrier for localized controlled delivery. Lactoferrin (LTf), a two-lobed protein, can deliver Ga3+ at sites of infection. This study aimed to develop a Ga-LTf complex for the treatment of wound infection. The characterisation of the Ga-LTf complex was conducted using differential scanning calorimetry (DSC), Infra-Red (FTIR) and Inductive Coupled Plasma Optical Emission Spectrometry (ICP-OES). The antibacterial activity was assessed by agar disc diffusion, liquid broth and biofilm inhibition assays using the colony forming units (CFUs). The healing capacity and biocompatibility were evaluated using a P.aeruginosa infected wound in a rat model. DSC analyses showed thermal transition consistent with apo-lactoferrin; FTIR confirmed the complexation of gallium to lactoferrin. ICP-OES confirmed the controlled local delivery of Ga3+. Ga-LTf showed a 0.57 log10 CFUs reduction at 24 h compared with untreated control in planktonic liquid broth assay. Ga-LTf showed the highest antibiofilm activity with a 2.24 log10 CFUs reduction at 24 h. Furthermore, Ga-LTf complex is biocompatible without any adverse effect on brain, kidney, liver and spleen of rats tested in this study. Ga-LTf can be potentially promising novel therapeutic agent to treat pathogenic bacterial infections

Innovative organotypic in vitro models for safety assessment: aligning with regulatory requirements and understanding models of the heart, skin, and liver as paradigms

The development of improved, innovative models for the detection of toxicity of drugs, chemicals, or chemicals in cosmetics is crucial to efficiently bring new products safely to market in a cost-effective and timely manner. In addition, improvement in models to detect toxicity may reduce the incidence of unexpected post-marketing toxicity and reduce or eliminate the need for animal testing. The safety of novel products of the pharmaceutical, chemical, or cosmetics industry must be assured; therefore, toxicological properties need to be assessed. Accepted methods for gathering the information required by law for approval of substances are often animal methods. To reduce, refine, and replace animal testing, innovative organotypic in vitro models have emerged. Such models appear at different levels of complexity ranging from simpler, self-organized three-dimensional (3D) cell cultures up to more advanced scaffold-based co-cultures consisting of multiple cell types. This review provides an overview of recent developments in the field of toxicity testing with in vitro models for three major organ types: heart, skin, and liver. This review also examines regulatory aspects of such models in Europe and the UK, and summarizes best practices to facilitate the acceptance and appropriate use of advanced in vitro models

Efficacy of a combination of Unani drugs in patients of Trichomonal vaginitis

727-730A controlled, randomized single blind clinical trial was conducted in women suffering from Trichomonal vaginitis. After confirming the clinical and microbiological diagnosis, the patients were divided into two groups. The patients in control group were administered Metronidazole in a dose of 200 mg three times a day, for seven days by oral route. While the patients in the test group were treated with a combination of Unani drugs, i.e. pills made of Afsanteen (Artemisia absinthium Linn.), Kabab Chini (Piper cubeba Linn.) and Bahroza (Pinus longifolia Roxb.) and capsule of Mazu (Gall of Quercus infectoria Oliv.), twice a day, for 10 days, by oral route. They were also treated with intravaginal tampon made of Barge Neem (Leaf of Azadirachta indica A. Juss.), Haldi (Rhizome of Curcuma longa Linn.) and Phitkiree (Alum), at bed time, for 10 days. The findings suggest that test drugs have been proved effective and safe in treatment of Trichomonal vaginitis

The distribution of small preantral follicles within the ovaries of prepubertal African elephants (Loxodonta africana)

BACKGROUND: Data on the distribution of primordial (single layer of squamous granulosa cells), early primary (some granulosa cells cuboidal) and primary (all granulosa cells cuboidal) follicles, grouped together as small follicles (SF) within the ovary of the elephant is lacking, yet such information is necessary to be able to estimate accurately the total numbers of small follicles in the ovaries of elephant throughout their lifespan. AIM: To determine if the density of SF differs between ovaries, between the surfaces of an ovary, or between the interpolar and intermarginal zones of an ovary. MATERIALS/METHODS: Stereological techniques were employed on 25 μm thick histological sections of the ovaries recovered from 12 prepubertal elephant calves aged 2 months to 4.5 years. Cell densities were calculated using the optical brick method and Cavalieri's principle for volume calculation. RESULTS: The density of SF (numbers of SF per unbiased counting frame [UCF]) did not differ between the left (1.11 ± 0.39 (mean ± sd)) and right (1.10 ± 0.39) ovaries (P = 0.82, n = 12), or between the lateral (median 1.24; interquartile range 0.85–1.39) and medial (1.03; 0.76–1.36) surfaces of the ovary (P = 0.22, n = 24) or among the 5 segments of the ovary between the two poles (P = 0.20, n = 24). The third of the cortex nearest to the mesovarial margin of the ovary had fewer small follicles per UCF (0.85; 0.51–1.28) than the middle third (1.01; 0.78–1.42; P = 0.034), and the third adjacent to the free margin (1.27; 0.79–1.51; P = 0.0024), n = 24 per group. CONCLUSION: Providing a random sample is taken from the full interpolar and intermarginal dimensions of ovary of a non-pregnant elephant, the density of small follicles throughout the cortex may be accurately measured using stereological techniques applied to one of its surfaces.http://www.elsevier.com/locate/anireprosciab201

Potential use of gallium-doped phosphate-based glass material for periodontitis treatment

This study aimed at evaluating the potential effect of gallium-incorporated phosphate-based glasses towards periodontitis-associated bacteria, Porphyromonas gingivalis, and matrix metalloproteinase-13. Periodontitis describes a group of inflammatory diseases of the gingiva and supporting structures of the periodontium. They are initiated by the accumulation of plaque bacteria, such as the putative periodontal pathogen Porphyromonas gingivalis, but the host immune response such as elevated matrix metalloproteinases are the major contributing factor for destruction of periodontal tissues. Antibacterial assays of gallium-incorporated phosphate-based glasses were conducted on Porphyromonas gingivalis ATCC 33277 using disc diffusion assay on fastidious anaerobe agar and liquid broth assay in a modified tryptic soy broth. In vitro study investigated the effect of gallium on purified recombinant human matrix metalloproteinase-13 activity using matrix metalloproteinase assay kit. In vivo biocompatibility of gallium-incorporated phosphate-based glass was evaluated in rats as subcutaneous implants. Antibacterial assay of gallium displayed activity against Porphyromonas gingivalis (inhibition zone of 22 ± 0.5 mm compared with 0 mm for control glass, c-PBG). Gallium in the glass contributed to growth inhibitory effect on Porphyromonas gingivalis (up to 1.30 reductions in log 10 values of the viable counts compared with control) in a modified tryptic soy broth. In vitro study showed gallium-incorporated phosphate-based glasses inhibited matrix metalloproteinase activity significantly ( p ≤ 0.01) compared with c-PBG. Evaluation of in vivo biocompatibility of gallium-incorporated phosphate-based glasses in rats showed a non-toxic and foreign body response after 2 weeks of implantation. The results indicate that gallium ions might act on multiple targets of biological mechanisms underlying periodontal disease. Moreover, gallium-incorporated phosphate-based glasses are biocompatible in a rat model. The findings warrant further investigation and will have important clinical implications in the future treatment and management of periodontitis. </jats:p

To Evaluate the Efficiency of ChatGPT in Medical Education: An Analysis of MCQ-Based Learning and Assessment

Objective: This study aimed to evaluate the potential of ChatGPT to help students for their assess ments via MCQ at different level of cognition by using different subjects of Internal medicine. Methods: This cross-sectional study was conducted in the Department of Internal Medicine in col laboration with post graduate medical education department from June 2023 to August 2023. An MCQ bank was established from three books of MCQ’s on subject of Internal Medicine. Total 1428 MCQ’s were followed for scrutiny and 307 MCQ’s were selected for the assigned task. The selected MCQ’s were manually entered one by one in a fresh Chat GPT session. The response was noted against the replies given in respective MCQ’s book and marked as correct, not correct or partially correct. MCQ’s were categorized as per chapters in Internal medicine and as per cognition level of MCQ’s i.e. C1, C2 and C3. Data was analyzed on SPSS version 21.00. Results: Chat GPT replied with 199 correct replies while 98 were wrong and 10 were partially correct. Chat GPT scored 64% overall in all categories. At level of cognition, it solved C2 MCQ’s by 80 % but scored 69% and 54% in C1 and C3 categories respectively. Chat GPT replied with 80% accuracy for C2 level MCQ’s while results were low for C3 category at around 54%. C1 also had low percentage of correct answers standing close to 69.8%. Almost all subjects showed healthy responses around the mean except for endocrinology and hematology where responses are below 60% and 40% respectively. Conclusion: This study findings suggest that ChatGPT is a useful tool for students and medical educationist with its current framework but a subtle approach should be inclined towards its role in future