ROS-responsive thioketal nanoparticles delivering system for targeted ulcerative colitis therapy with potent HDAC6 inhibitor, tubastatin A.

Ulcerative colitis (UC) is a common gastrointestinal problem characterized by the mucosal injury primarily affecting the large intestine. Currently available therapies are not satisfactory as evidenced by high relapse rate and adverse effects. In this study we aimed to develop an effective drug delivery system using reactive oxygen species (ROS)-responsive thioketal nanoparticles (TKNP), to deliver tubastatin A, a potent HDAC6 inhibitor, to the inflamed colon in mice with ulcerative colitis (UC). TKNPs were synthesized by step-growth polymerization from an acetal exchange reaction while TUBA-TKNP was prepared using the single emulsion solvent evaporation technique. Our developed nanoparticle showed release of tubastatin A only in presence of ROS which is found to be highly present at the site of inflamed colon. Oral administration of TUBA-TKNP resulted in the higher accumulation of tubastatin A at the inflamed colon site and decreased the inflammation as evidenced by reduced infiltration of immune cells and decreased level of pro-inflammatory cytokines in TUBA-TKNP treated mice. In summary, our results show the successful localization of tubastatin A at the site of colon inflammation through TUBA-TKNP delivery, as well as resolution of clinical features of UC in mice.

Edentulousness among Patients Visiting a Dental Unit of a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Edentulousness (partial or complete) is a sequel of tooth loss and is an indicator of the oral health status of a population. Edentulousness has a series of deleterious consequences for oral and general health. The aim of this study was to find out the prevalence of edentulousness among patients visiting the dental unit of a tertiary care centre. Methods: A descriptive cross-sectional study was carried out based on hospital records of patients visiting the Department of Oral Medicine and Prosthodontics of a tertiary care centre from 1 January 2019 to 30 December 2019 to see the prevalence of edentulousness. Ethical approval was obtained from the Institutional Review Committee (Reference number: 077/ 078 /40). A convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated. Results: Among 4697 patients, edentulousness was found in 403 (8.58%) (7.78-9.38, 95% Confidence Interval). Partial edentulous were 263 (65.30%) and complete edentulous were 140 (34.70%). Of the total partial edentulous patient, Kennedy's class III found in 200 (76.05%) was the most common pattern followed by Kennedy's class I in 32 (12.17%), class II in 21 (7.98%) and class IV in 10 (3.80%) patients respectively. Conclusions: The prevalence of edentulousness was similar to other studies done in similar settings. Since edentulousness is a preventable problem, it should be addressed with high priority. Keywords: dental health service; edentulous mouth; Nepal; prevalence.

Methamphetamine induced neurotoxic diseases, molecular mechanism, and current treatment strategies.

Methamphetamine (MA) is a extremely addictive psychostimulant drug with a significant abuse potential. Long-term MA exposure can induce neurotoxic effects through oxidative stress, mitochondrial functional impairment, endoplasmic reticulum stress, the activation of astrocytes and microglial cells, axonal transport barriers, autophagy, and apoptosis. However, the molecular and cellular mechanisms underlying MA-induced neurotoxicity remain unclear. MA abuse increases the chances of developing neurotoxic conditions such as Parkinson's disease (PD), Alzheimer's disease (AD) and other neurotoxic diseases. MA increases the risk of PD by increasing the expression of alpha-synuclein (ASYN). Furthermore, MA abuse is linked to high chances of developing AD and subsequent neurodegeneration due to biological variations in the brain region or genetic and epigenetic variations. To date, there is no Food and Drug Administration (FDA)-approved therapy for MA-induced neurotoxicity, although many studies are being conducted to develop effective therapeutic strategies. Most current studies are now focused on developing therapies to diminish the neurotoxic effects of MA, based on the underlying mechanism of neurotoxicity. This review article highlights current research on several therapeutic techniques targeting multiple pathways to reduce the neurotoxic effects of MA in the brain, as well as the putative mechanism of MA-induced neurotoxicity.

Anterior Tooth Width Measurements among Patients in a Tertiary Hospital of Nepal: A Descriptive Cross-sectional Study.

INTRODUCTION: The knowledge of anterior tooth width and their relationships with each other is essential for any esthetic and prosthodontic rehabilitation. The objective of this study is to measure the width of the anterior teeth of patients coming to a teritary hospital of Nepal. METHODS: This descriptive cross-sectional study was conducted at a tertiary care hospital from 30th September 2019 to 30th October 2019 after receiving ethical clearance from the institutional review committee (reference number: 2076/77/20). Convenient sampling was done. Point estimate at 99% Confidence Interval was calculated along with frequency and proportion for binary data. Data analysis was done in Statistical Package for the Social Sciences version 21. RESULTS: Out of the 40 participants, the mean width of right and left side of anterior teeth of the maxillary central incisors were 8.62±0.62 mm and 8.65±0.55 mm; maxillary lateral incisors were 6.97±0.74 mm and 7.11±0.78 mm; maxillary canine were 7.81±0.69 mm and 8.15±0.72 mm; mandibular central incisors were 5.37±0.4 mm and 5.43±0.37 mm; mandibular lateral incisors were 5.88±.52 mm and 6.06±0.53 mm; mandibular canine were 6.69±0.55 mm and 6.93±0.7 mm respectively. The difference between the teeth was compared with the central incisors of each side. CONCLUSIONS: Our findings of the average values of the anterior teeth and their difference from the central incisors on each side showed an agreement with the optimal relationships of anterior teeth, with the exception of the maxillary lateral incisors, which were 0.5mm larger than the values of the optimal relationship.