Origin of Enhancement of Orbital Magnetic Moment in SiO2-Coated Fe3O4 Nanocomposites Studied by X-ray Magnetic Circular Dichroism.

In this study, magnetic Fe3O4 nanoparticles (NPs) were dispersed uniformly by varying the thickness of the SiO2 coating, and their electronic and magnetic properties were investigated. X-ray diffraction confirmed the structural configuration of monophase inverse-spinel Fe3O4 NPs in nanometer size. Scanning electron microscopy revealed the formation of proper nonporous crystallite particles with a clear core-shell structure with silica on the surface of Fe3O4 NPs. The absorption mechanism studied through the zeta potential indicates that SiO2-coated Fe3O4 nanocomposites (SiO2@Fe3O4 NCs) possess electrostatic interactions to control their agglomeration in stabilizing suspensions by providing a protective shield of amorphous SiO2 on the oxide surface. High-resolution transmission electron microscopy images demonstrate a spherical morphology having an average grain diameter of ∼11-17 nm with increasing thickness of SiO2 coating with the addition of a quantitative presence and proportion of elements determined through elemental mapping and electron energy loss spectroscopy studies. Synchrotron-based element-specific soft X-ray absorption spectroscopy and X-ray magnetic circular dichroism (XMCD) techniques have been involved in the bulk-sensitive total fluorescence yield mode to understand the origin of magnetization in SiO2@Fe3O4 NCs. The magnetization hysteresis of Fe3O4 was determined by XMCD. At room temperature, the magnetic coercivity (Hc) is as high as 1 T, which is about 2 times more than the value of the thin film and about 5 times more pronounced than that of NPs. For noninteracting single-domain NPs with the Hc spread from 1 to 3 T, the Stoner-Wohlfarth model provided an intriguing explanation for the hysteresis curve. These curves determine the different components of Fe oxides present in the samples that derive the remnant magnetization involved in each oxidation state of Fe and clarify which Fe component is responsible for the resultant magnetism and magnetocrystalline anisotropy based on noninteracting single-domain particles.

Synthesis of oligonucleotides containing 5'-homo-4'-selenouridine derivative and its increased resistance against nuclease.

As technologies using RNA or DNA have been developed, various chemical modifications of nucleosides have been attempted to increase the stability of oligonucleotides. Since it is known that 2'-OMe-modification greatly contributes to increasing the stability of oligonucleotides, we added 2'-OMe to our previously developed 4'-selenonucleoside and 5'-homo-4'-selenonucleoside as the modified monomers for oligonucleotide: 2'-methoxy-4'-selenouridine (2'-OMe-4'-Se-U) and 5'-homo-2'-methoxy-4'-selenouridine (5'-homo-2'-OMe-4'-Se-U). We synthesized oligonucleotides containing the chemically modified 4'-selenouridine and evaluated their thermal stability and nuclease resistance. In conclusion, the nuclease stability of the oligonucleotide containing 5'-homo-2'-OMe-4'-selenouridine increased while its thermal stability decreased.

Fluorine-a small magic bullet atom in the drug development: perspective to FDA approved and COVID-19 recommended drugs.

During the last twenty years, organic fluorination chemistry established itself as an important tool to get a biologically active compound. This belief can be supported by the fact that every year, we are getting fluorinated drugs in the market in extremely significant numbers. Last year, also ten fluorinated drugs have been approved by FDA and during the COVID-19 pandemic, fluorinated drugs played a very crucial role to control the disease and saved many lives. In this review, we surveyed all ten fluorinated drugs approved by FDA in 2021 and all fluorinated drugs which were directly-indirectly used during the COVID-19 period, and emphasis has been given particularly to their synthesis, medicinal chemistry, and development process. Out of ten approved drugs, one drug pylarify, a radioactive diagnostic agent for cancer was approved for use in positron emission tomography imaging. Also, very briefly outlined the significance of fluorinated drugs through their physical, and chemical properties and their effect on drug development.

Fluorinated Nucleosides: Synthesis, Modulation in Conformation and Therapeutic Application.

Over the last twenty years, fluorination on nucleoside has established itself as the most promising tool to use to get biologically active compounds that could sustain the clinical trial by affecting the pharmacodynamics and pharmacokinetic properties. Due to fluorine's inherent unique properties and its judicious introduction into the molecule, makes the corresponding nucleoside metabolically very stable, lipophilic, and opens a new site of intermolecular binding. Fluorination on various nucleosides has been extensively studied as a result, a series of fluorinated nucleosides come up for different therapeutic uses which are either approved by the FDA or under the advanced stage of the clinical trial. Here in this review, we are summarizing the latest development in the chemistry of fluorination on nucleoside that led to varieties of new analogs like carbocyclic, acyclic, and conformationally biased nucleoside and their biological properties, the influence of fluorine on conformation, oligonucleotide stability, and their use in therapeutics.

Histopathological Changes in Oral Tissues Induced by Pesticide Poisoning: A Pilot Study.

OBJECTIVE: The present study evaluated the histopathological changes in oral tissues induced by pesticide poisoning. PATIENTS AND METHODS: This was a cross-sectional pilot study. The sample consisted of oral tissues obtained from deceased patients during autopsy. The study samples were obtained from 10 cases of ingested pesticide poisoning, and the control samples were obtained from road traffic accident cases. All the obtained samples were subjected to histopathological examinations. The changes observed in poisoning cases were compared to those in the road traffic accident cases. RESULTS: Significant degenerative changes were observed in the epithelial cells and connective tissue components, such as collagen, muscles, nerves, vasculature, adipose tissue, and salivary acini and ducts, in the poisoning cases. The oral tissues of the road traffic accident cases did not show any significant degenerative changes. CONCLUSION: The degenerative changes in the study samples can be attributed to the direct contact of the pesticide with the autopsied oral tissues when the poison was consumed. There are instances in which the entire body may not be recovered or may not be in an examinable state. In such cases, an oral autopsy could provide additional evidence for determining the cause of death in suspected poison cases.

Association of -330 interleukin-2 gene polymorphism with oral cancer.

BACKGROUND & OBJECTIVES: Cytokines play an important role in the development of cancer. Several single-nucleotide polymorphisms (SNPs) of cytokine genes have been reported to be associated with the development and severity of inflammatory diseases and cancer predisposition. This study was undertaken to evaluate a possible association of interleukin 2 (IL-2) (- 330A>C) gene polymorphisms with the susceptibility to oral cancer. METHODS: The SNP in IL-2 (-330A>C) gene was genotyped in 300 oral cancer patients and in similar number of healthy volunteers by polymerase chain reaction (PCR)-restriction fragment length polymorphism and the association of the gene with the disease was evaluated. RESULTS: IL-2 (-330A>C) gene polymorphism was significantly associated with oral cancer whereas it was neither associated with clinicopathological status nor with cancer pain. The AC heterozygous genotype was significantly associated with oral cancer patients as compared to controls [odds ratio (OR): 3.0; confidence interval (CI): 2.14-4.20; P<0.001]. The C allele frequency was also significantly associated with oral cancer (OR: 1.80; CI: 1.39-2.33; P<0.001). IL-2 (-330A>C) gene polymorphism was also associated with oral cancer in tobacco smokers and chewers. INTERPRETATION & CONCLUSIONS: Our results showed that oral cancer patients had significantly higher frequency of AA genotype but significantly lower frequency of AC genotype and C allele compared to controls. The IL-2 AC genotype and C allele of IL-2 (-330A>C) gene polymorphisms could be potential protective factors and might reduce the risk of oral cancer in Indian population.

Establishing a deceased donor program in north Indian region: lessons learnt.

INTRODUCTION: Living-related donors are the source of almost all organ transplants in India. However, these donations fall far short of current needs, and there remains a huge disparity between demand and supply of organs. In the last five yr, a consistent increase in deceased donor transplant activity has been observed in some southern Indian states. This report describes our experience of establishing a new deceased donor program in the state of Uttar Pradesh in north India. METHODS: We describe our experience on counseling families of all brain-dead patients admitted to our center from October 2013 to September 2014 and data on retrieving and transplanting organs. RESULTS: A total of 99 brain-dead patients were identified, of which 67 were medically eligible as donors. Fourteen patients developed cardiac arrest before the counseling could begin. Only eight families agreed for multi-organ donation. CONCLUSION: Lack of consensus among the family members, mistrust of the medical system, fear of mutilation of the body, and delay in the funeral were identified as the main reasons behind negative consent. Conversely, mass media campaign, proper ICU care of brain-dead patients, rapport with the family and streamlining all medico legal processes were associated with positive consent.

Association of Genetic Polymorphism in the Interleukin-8 Gene with Risk of Oral Cancer and Its Correlation with Pain.

Oral cancer is a multifactorial disease process and involves complex interactions between gene to gene and gene to environmental factors. Interleukin 8 (IL-8), a pro-inflammatory cytokine, having angiogenic activity with elevated expression in tumor cells, is reported to play an essential role in oral cancer development. This study was conducted with the aim to investigate the role of IL-8 (-A251T) gene polymorphism in susceptibility, progression, and self-reporting pain in oral cancer. The single nucleotide polymorphisms of the IL-8 (-A251T) gene were screened in 300 patients with oral cancer and 300 healthy controls, by polymerase chain reaction-restriction fragment length polymorphism. Genotype and allele frequencies were evaluated by chi-square test and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. The results of the study demonstrated that IL-8 (-A251T) gene polymorphism was significantly associated with susceptibility of oral cancer, whereas its correlation with clinico-pathological status or pain due to oral cancer could not be established. The AT heterozygous (OR 5.31; CI 3.38-8.34; p 0.0001) and AA homozygous (OR 2.89; CI 1.76-4.75; p 0.0001) had a greater risk for oral cancer compared to TT homozygous. Furthermore, significantly increased values of A allele frequencies compared to T allele were observed in all patients (OR 1.56; CI 1.24-1.96; p 0.0002). Tobacco chewing and smoking were also found to influence the development of oral cancer and increased the incidence of pain in oral cancer patients. The findings of this study suggest that the IL-8 (-A251T) gene polymorphism may be associated with increased risk of oral cancer.

Effects of interleukin-18 promoter (C607A and G137C) gene polymorphisms and their association with oral squamous cell carcinoma (OSCC) in northern India.

Interleukin-18 (IL-18) is one of the immunomodulatory cytokines that plays an important role in cellular functions against tumor development and progression. IL-18 (-607) C/A and (-0137) G/C gene promoter polymorphisms and their haplotypes variants are associated with risk of various cancers. We evaluated a possible association of IL-18 (-607) C/A and (-137) G/C gene promoter polymorphisms in the susceptibility to oral squamous cell carcinoma (OSCC). A total number of 272 patients with OSCC and 185 healthy volunteers were genotyped for the IL-18 (-607) C/A and (-137) G/C polymorphism. Polymorphism variants were examined by using tetra-primer amplification refractory mutation system (T-ARMS). Genotype frequencies were evaluated by chi-square test and odds ratio (OR) relative risk. IL-18 (-137) G/C gene polymorphism was significantly associated with the risk of OSCC as compared to healthy volunteers (genotype GG vs GC: OR 2.238; 95 % CI 1.455-3.441; p = 0.0003 and allele G vs C: OR 1.984; 95 % CI 1.335-2.947; p = 0.0007). The genotype and allele frequencies of the IL-18 promoter -607 C/A polymorphism in OSCC patients were not significantly different than that in healthy controls (p > 0.05). Our results suggest that IL-18 -137 G/C polymorphism is significantly associated with the progression of oral cancer but -607 C/A polymorphism is not associated with this.

A comparative evaluation of analgo-sedative effects of oral dexmedetomidine and ketamine: a triple-blind, randomized study.

BACKGROUND: Use of sedative agents for difficult to manage children during dental procedures has been indicated for years, but neither the agent nor the route has been found to be ideal. OBJECTIVES: The aim of the study was to evaluate and compare the efficacy and safety of oral dexmedetomidine (D) and ketamine (K) in producing moderate sedation among uncooperative pediatric dental patients. METHODS: This prospective, triple-blind, randomized comparative study included 112 ASA grade I children of both sexes aged 3-10 years, who satisfied all the inclusion criteria. They were randomly divided into four groups and ketamine 8 mg·kg(-1) (K) or dexmedetomidine 3 µg·kg(-1) (D1), 4 µg·kg(-1) (D2) and 5 µg·kg(-1) (D3) were given orally. Similar dental procedures were performed in these patients, and effects of these drugs were assessed in terms of changes in vital signs, onset and duration of sedation, analgesia, and amnesia. Secondary outcomes such as level of sedation, behavior, adverse effects, and overall success were also measured. RESULTS: The onset of sedation was significantly rapid with K and D3 as compared to D1 and D2. Recovery from sedation was fastest in group D1. Intra- and postoperative analgesia and anterograde amnesia were highest with K and least with D1, while D3 produced analgesia comparable to K. In K treated group, vomiting was observed in five patients and two patients exhibited emergence phenomenon. Overall, highest success rate was observed in D3 group. CONCLUSIONS: Given by oral route, the novel sedative dexmedetomidine provides dose-dependent effective analgo-sedation, comparable to ketamine, with less adverse effects.

Flap sub-domain dynamics of serine-threonine phosphatase (Stp1) of Staphylococcus aureus: an accelerated molecular dynamics simulation study.

Vancomycin and daptomycin are commonly used glycopeptide antibiotics to cure Gram-positive staphylococcal infections. The clinical isolates of mutant Staphylococcus aureus strains, Methicillin-Resistant (MRSA) and Vancomycin-Resistant (VRSA), have developed resistance against these antibiotics. A recently discovered Serine/threonine phosphatase (Stp1) is an Mn+2 containing protein at the active site with a flap sub-domain that participates in the phospho-signaling system of bacterial cell wall formation. The flap sub-domain probably regulates substrates recruitment and release with an extra Mn+2, possibly highly flexible as in the other homologous family of proteins. In this study, the flap sub-domain has been sampled with conventional and accelerated molecular dynamics (cMD and aMD) simulations to get other sub-optimal conformational states of the protein that are nearly impossible to observe through experimental methods. Trajectory analysis has shown that protein remained static in cMD while dynamic in aMD with RMSD of ∼2Å and ∼3Å, respectively. Accelerated MD has shown greater flexibility of ∼4 Å in the flap sub-domain, while cMD only captured a deviation of ∼ 2 Å. Later, the dynamic cross-correlation map (DCCM) confirmed that the flap sub-domain is significantly more flexible than the other part of the structure, indicating its role in substrate regulation. Secondary structure transition in the flap sub-domain, i.e. 3-10 helix and turn (PRO159 - ILE163) region of the flap sub-domain shifted into α-helix, which is a more stable structure. Further, the trajectory has been clustered, and conformational states extracted, which may be exploited in structure-based antibiotics discovery.Communicated by Ramaswamy H. Sarma.

Finite element method-based simulation on bone fracture fixation configuration factors for biodegradable embossed locking compression plate.

As an evolution, biodegradable implants need to maximize mechanical performance thereby may lead to confusion in selection of the biodegradable material and implant design to the fracture site. This requires selecting a unique fixation configuration to fit within the fractured bone, factors of which can be bone-plate clearance, interfragmentary gap, alteration in screw fixation position and variation in the number of screws whose configuration optimization can re-maximize the mechanical performance of the biodegradable implant. Therefore, these factors have been optimized based on the induced minimum stress using the finite element method-based simulation for which biodegradable embossed locking plates (BELCP) via screws made of Mg-alloy have been fitted over two fragments of femur body (as hollow cylindrical cortical bone). An average human weight of 62 kg is applied to one segment of the femur for all different configurations of each factor, where another segment is assumed to be fixed. By this simulation, the most optimal fixation configuration was found at a minimum induced stress value of 41.96 MPa which is approximately 85%, 18%, 6% and 48% respectively less than all maximum stress induced configurations in each of the factor. This optimized configuration was at the minimum clearance between bone and plate with a 3 mm interfragmentary gap using 8 screws where the locking screw begins to apply from the center of the BELCP. Overall, BELCP may be a better biodegradable implant plate for bone fracture fixation with these optimized fixation configurations as the improved mechanical performance after experimental validation.

Biomechanical evaluation on a novel design of biodegradable embossed locking compression plate for orthopaedic applications using finite element analysis.

In orthopaedics, conventional implant plates such as locking compression plate (LCP) made from non-biodegradable materials play a vital role in the fixation to support bone fractures, but also create a complication such as stress shielding. These again require a painful surgery to remove/replace after they have healed as it does not degrade into the physiological environment (PE). Currently, there has already been enough discovery of biodegradable materials that, despite being mechanically inefficient compared to non-biodegradable materials, can completely be biodegraded in PE during and after healing to avoid such problems. While there has been insufficient research on the design of biodegradable implant plates, the implementation of which may help achieve the goal with an effort of high mechanical strength. A novel design of biodegradable embossed locking compression plate (BELCP) is designed for biodegradable materials to approach superior mechanical performance and complete degradation over time, considering all such parameters and factors. For biomechanical evaluation, four-point bending test (4PBT), axial compressive and tensile test (ACTT) and torsion test (TT) have been performed on LCP, BELCP and its continuously degraded forms made of biodegradable material (Mg-alloy) using finite element method. BELCP has found 50%, 100% and 100% higher mechanical performance and safer in 4PBT, ACTT and TT, respectively, than LCP. Moreover, BELCP has also observed safe during continuous degradation up to 6 months after implantation under these three tests, considering an approximate sustained degradation rate of about 4 mm/year. Even Mg-alloy made BELCP can be sufficient and safer to support fractured bone than SS-alloy made LCP, but not Ti-alloy made LCP. BELCP can be a successful biodegradable bone implant plate after human/animal trials in the future.

Effectiveness of laddered embossed structure in a locking compression plate for biodegradable orthopaedic implants.

Locking compression plate (LCP) has conventionally been the most extensively employed plate in internal fixation bone implants used in orthopaedic applications. LCP is usually made up of non-biodegradable materials that have a higher mechanical capability. Biodegradable materials, by and large, have less mechanical strength at the point of implantation and lose strength even more after a few months of continuous degradation in the physiological environment. To attain the adequate mechanical capability of a biodegradable bone implant plate, LCP has been modified by adding laddered - type semicircular filleted embossed structure. This improved design may be named as laddered embossed locking compression plate (LELCP). It is likely to provide additional mechanical strength with the most eligible biodegradable material, namely, Mg-alloy, even after continuous degradation that results in diminished thickness. For mechanical validation and comparison of LELCP made up of Mg-alloy, four-point bending test (4PBT) and axial compressive test (ACT) have been performed on LELCP, LCP and continuously degraded LELCP (CD-LELCP) with the aid of finite element method (FEM) for the assembly of bone segments, plate and screw segments. LELCP, when subjected to the above mentioned two tests, has been observed to provide 26% and 10.4% lower equivalent stress, respectively, than LCP without degradation. It is also observed mechanically safe and capable of up to 2 and 6 months of continuous degradation (uniform reduction in thickness) for 4PBT and ACT, respectively. These results have also been found reasonably accurate through real-time surgical simulations by approaching the most optimal mesh. According to these improved mechanical performance parameters, LELCP may be used or considered as a viable biodegradable implant plate option in the future after real life or in vivo validation.

Effectiveness of non-uniform thickness on a locking compression plate used as a biodegradable bone implant plate.

Conventional locking compression plate (LCP) made of non-biodegradable materials are well-known bone implants for internal fracture fixation because of their proven experimental success. LCP, however, is mechanically underpowered when made up of biodegradable materials (even with Mg-alloy). The biodegradable implant plate should not only exhibit adequate mechanical performance during implantation but also perform well after fracture, at least until complete healing of the fractured bone. With the aim of achieving enhanced mechanical performance, the design of the LCP has been modified to the design of Biodegradable Locking Compression Plate (BLCP) by adding a suitable thickness in the middle (only 4.6% of the total volume of the LCP), which may help retain some additional strength during implantation and after degradation. Both BLCP and LCP have been comparatively analyzed via FEM with the aid of axial compression and four-point bending tests. BLCP has a better mechanical capability of withstanding loads in its degraded form than in its non-degradable form. Furthermore, BLCP is up to 15.83% mechanically better in the non-degraded form as compared to LCP, which again becomes up to 100% more mechanically adequate in the degraded forms of BLCP than in LCP. BLCP is found safe for degradation up to 2 mm or 6 months with an estimated degradation rate of 4 mm/year, which may allow it to support fractured bone for at least the standard healing time. BLCP can be considered as a superior biodegradable bone implant plate after experimental assurance with the physiological environment and may replace LCP.

Microstructure, Mechanical, In Vitro Biodegradation, and Antimicrobial Behavior of a Mg-Zn-Ca-Sr/ZrO2 Composite Prepared Using Powder Metallurgy.

Biodegradable materials, especially Mg alloys, have an exceptional advantage over nonbiodegradable materials in orthopedic applications, such as avoiding second surgery for removal/replacement, stress shielding, but not enough mechanical strength, and so forth. By further improving the Mg alloy to get all the remaining required properties, it can be used for better biodegradable implants, which depend adequately on material optimization, processing, and so forth. A Mg-Zn-Ca-Sr/ZrO2 composite has been prepared using powder metallurgy by adding 0, 1, 2, and 3 wt % of ZrO2, which also contains Zn, Ca, and Sr as nutrient elements. Microstructure characterization, as well as mechanical and in vitro biodegradation, have been investigated by hardness, compression, and immersion tests. The highest compressive strength, contraction, and hardness of about 185.6 MPa, 9.5%, and 65.2 HRB are observed in the 2% ZrO2-containing composite, respectively, whereas a minimum biodegradation rate of 2.76 mm/year is observed on the same. The antibiotic sensitivity observations against Staphylococcus aureus suggest that the alloy C3 has superior biological activity against the pathogen which ranks this alloy on top in merit. Overall, Mg-Zn-Ca-Sr/ZrO2 exhibits impressive potential for use as a biodegradable and antibiotic material for orthopedic applications.

Longitudinally centered embossed structure in the locking compression plate for biodegradable bone implant plate: a finite element analysis.

In the current revolution of internal fixation implant in orthopaedics, a biodegradable implant is the most awaited and exceptional medical device where biodegradable material has paid more attention to the success of a biodegradable implant than the design of a biodegradable bone implant plate. By far, LCP is the most traditionally used implant plate (using non-biodegradable material) because of its experimental success, but not with qualified biodegradable material (Mg-alloy). This lack of mechanical performance is a major drawback that can be rectified by better structural design. This will help avoid few other problems as well. Therefore, with proper consideration, the LCP has been added to a semicircular filleted longitudinally centered embossed (LCE) structure to enhance overall mechanical performance that can help emphasize mechanical support even after continuous degradation when applied in a physiological environment. For mechanical verification of this advanced design of biodegradable bone implant plate, four-point bending test (4PBT) and axial compression test (ACT) have been performed using FEM on LCELCP, LCP, continuously degraded (CD)-LCELCP, and CD-LCP. LCELCP showed reduced stress of about 22% and 10% in 4PBT and ACT, respectively, compared to LCP. CD-LCELCP is safe during ACT over 6 months of continuous degradation when the degradation rate is assumed to be 4 mm/year. These results also ensured accuracy using mesh convergence and also mesh checked for quality assurance. Overall, LCELCP can be considered as a biodegradable bone implant plate because of its superior performance, if its ultimate validation is carried out through animal/human trials as future work.

Regio- and stereoselective synthesis of truncated 3'-aminocarbanucleosides and their binding affinity at the A3 adenosine receptor.

The stereoselective synthesis of truncated 3'-aminocarbanucleosides 4a-d via a stereo- and regioselective conversion of a diol 9 to bromoacetate 11a and their binding affinity towards the human A(3) adenosine receptor are described.

A comparative evaluation of drops versus atomized administration of intranasal ketamine for the procedural sedation of young uncooperative pediatric dental patients: a prospective crossover trial.

OBJECTIVE: The objective of this study was to compare and evaluate the efficacy and safety of drops and atomized administration of intranasal ketamine (INK) in terms of behavioral response for agent acceptance during administration and for agent efficacy and safety for the sedation of young uncooperative pediatric dental patients. STUDY DESIGN: Thirty-four uncooperative ASA grade-1 children, requiring dental treatment were randomly assigned to receive INK as drops and atomized spray in one of the subsequent visit. This was a two stage cross-over trial and each child received INK by both modes of administration. The vital signs were monitored continuously during each visit. RESULTS: A statistically significant difference in patients acceptance (P < 0.0001) was observed in the atomized administration when compared to drops administration for the procedural event of drug administration. Moreover there were also significant differences (P < 0.05) between onset of sedation and recovery time between two groups. All the vital signs were within normal physiological limits and there were no significant adverse effects in either group. CONCLUSIONS: INK is safe and effective by either mode of intranasal (IN) drug administration for moderate sedation in facilitating dental care for anxious and uncooperative pediatric dental patients. Moreover, INK when administered with the mucosal atomization device, the acceptance of the drug was associated with less aversive reaction, rapid onset and recovery of sedation, as compared to the drop administration of the same agent.

A comparative evaluation of intranasal midazolam, ketamine and their combination for sedation of young uncooperative pediatric dental patients: a triple blind randomized crossover trial.

OBJECTIVE: The purpose of this study was to evaluate and compare the efficacy and safety of intranasal (IN) administration of midazolam (M), ketamine (K) and their combination (MK) to produce moderate sedation in young, uncooperative pediatric dental patients. STUDY DESIGN: In this three stage crossover trial forty five uncooperative ASA type-1 children, who required dental treatment, were randomly assigned to receive one of the three drugs/combination by IN route during three subsequent visits. The efficacy and safety of the agents were assessed by overall success rate and by monitoring of vital signs, respectively. RESULTS: The onset of sedation was rapid with K as compared to M and MK. The difference was statistically significant (P < 0.01) between K and M. The overall success rate was 89% with K, MK was 84% and 69% with M. The difference between the overall success rates of K and M was statistically significant (P < 0.01). Vital signs were within physiological limits and there were no significant adverse effects with any medication. CONCLUSIONS: M, K and MK are safe and effective by IN route to produce moderate sedation for providing dental care to pediatric dental patients who have been otherwise indicated for treatment under general anesthesia.