ABSTRACT
Amphiphilic azobenzene molecules offer ample scope to design functional supramolecular systems in an aqueous medium that can be controlled by light. Despite their widespread applications in photopharmacology and optoelectronics, the self-assembly pathways and energy landscapes of these systems are not well understood. Here, we report combined molecular dynamics (MD) simulation and surface manometry studies on a specially designed alkylated, meta-substituted azobenzene derivative to quantify the hydrogen-bonding interactions in the self-assembled monolayers of its photoisomers. The z-density profile, radial distribution function, order parameters, and hydrogen bond analyzed using MD simulations corroborated the experimental observations of changes in surface pressure, dipole moment, and thickness of the monolayers. Even a small change in the number of hydrogen bonds in the molecule-molecule and molecule-water interactions causes significant changes in the monolayer properties. These results are fundamentally important for engineering photoresponsive molecules with tailored properties for applications in targeted drug delivery and other industrial applications.
ABSTRACT
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 â¼11-17 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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Oligonucleotides , Organoselenium Compounds , Oligonucleotides/genetics , Organoselenium Compounds/pharmacology , RNA , UridineABSTRACT
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 â¼2Å and â¼3Å, respectively. Accelerated MD has shown greater flexibility of â¼4 Å in the flap sub-domain, while cMD only captured a deviation of â¼ 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.
Subject(s)
Staphylococcal Infections , Staphylococcus aureus , Humans , Vancomycin , Molecular Dynamics Simulation , Microbial Sensitivity Tests , Staphylococcal Infections/microbiology , Anti-Bacterial Agents/pharmacology , Phosphoprotein Phosphatases/chemistry , Phosphoprotein Phosphatases/metabolismABSTRACT
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.
Subject(s)
Anti-Infective Agents , Magnesium , Magnesium/chemistry , Powders , Materials Testing , Zinc/chemistry , Alloys/chemistry , Strontium/chemistry , Metallurgy , Anti-Bacterial Agents/pharmacologyABSTRACT
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.
Subject(s)
Fracture Fixation, Internal , Orthopedics , Animals , Humans , Finite Element Analysis , Fracture Fixation, Internal/methods , Stress, Mechanical , Biomechanical Phenomena , Bone Plates , AlloysABSTRACT
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.
Subject(s)
Absorbable Implants , Bone Plates , Biomechanical Phenomena , Bone and Bones , Fracture Fixation, Internal , PressureABSTRACT
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.
Subject(s)
Fluorine , Nucleosides , Fluorine/chemistry , Molecular Conformation , Nucleosides/chemistry , Nucleosides/pharmacologyABSTRACT
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.
Subject(s)
Absorbable Implants , Bone Plates , Animals , Biomechanical Phenomena , Finite Element Analysis , Fracture Fixation, Internal/methodsABSTRACT
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.
Subject(s)
Orthopedics , Absorbable Implants , Biomechanical Phenomena , Bone Plates , Bone Screws , Fracture Fixation, Internal/methodsABSTRACT
Introduction: Biodegradable materials have been at the forefront of cutting-edge research and offer a truly viable option in the designing and manufacturing of bone implants in biomedical engineering. Most research regarding these materials has focused on their biological characteristics and mechanical behavior vis-à-vis nonbiodegradable (NB) materials; but the design aspects and parametric configurations of biodegradable bone implant have somehow not received as much attention as they deserved.Area covered: This review aims to develop insight into the parametrically conceptualized design of biodegradable bone implant and takes into due consideration the characteristics of bone-biodegradable implant interface (BBII), design techniques employed for conventionally used bone implants to optimize parameters using standard test methods, traditional design, and finite element analysis approaches for implant and healing behavior, manufacturing techniques, real-time surgical simulations, and so on.Expert opinion: Some successful and conventionally used NB bone implants do not dissolve or degrade with time and require removal through a complicated surgery after fulfilling the intended objectives. These bone implants should be reconceptualized and designed with an appropriate biodegradable material while paying due attention to all factors/parameters involved and striking a balance between these factors with the ultimate objective of fulfilling all desired orthopedic requirements.
Subject(s)
Absorbable Implants , Biocompatible Materials , Bone and Bones , Finite Element Analysis , HumansABSTRACT
Screws made up of non-biodegradable materials (Ti-alloy, etc.) have been used since long for temporary joining/fixation in applications involving skeleton damage or bone fracture. These screws need to be removed after complete healing as their sustained presence results in many complications, such as - micro-fracturing, stress shielding, etc. The removal of these screws is a little difficult too as it may result in the healed bone getting broken/damaged again. These problems can be overcome by employing metallic implants (plate, screws, etc.) made up of biodegradable metallic materials (Mg-alloy, etc.). Such implants exhibit optimal mechanical performance, are biocompatible, have adequate biodegradation rates, and rely on a unique design. Internal fracture fixation makes usage of screws with or without an accompanying plate. Buttress-threaded screws are the most frequently used ones. These screws must have the capacity to bear usually occurring loads and hold fractured segments of bone all through the process of healing. Finite element analysis (FEA) is an effective technique used for testing and validation of desired characteristics for Mg-based biodegradable buttress-threaded screw (BBTS). The characteristics of interest include maximum possible pullout resistance to tightly hold segments of bone, torsional ability for tightening or tapping, bending ability during providing plate support by screw head, and resistance to combined loading (tensile/compressive and bending) during the self-support stage using merely the screw(s). According to test results and subsequent validation through discretization error and convergence plot, BBTS made up of Mg-alloy are found safe for regular applications under usually encountered impact loads. Topological optimization and vibration analysis are also performed wherein it is observed that design of BBTS is good enough for possible usage in fracture fixation in orthopaedics.
Subject(s)
Fractures, Bone , Orthopedics , Alloys , Bone Screws , Finite Element Analysis , Fracture Fixation , Fractures, Bone/surgery , HumansABSTRACT
Success of targeted cancer treatment modalities has generated an ambience of plausible cure for cancer. However, cancer remains to be the major cause of mortality across the globe. The emergence of chemoresistance, relapse after treatment and associated adverse effects has posed challenges to the present therapeutic regimes. Thus, investigating new therapeutic agents of natural origin and delineating the underlying mechanism of action is necessary. Since ages and still in continuum, the phytochemicals have been the prime source of identifying bioactive agents against cancer. They have been exploited for isolating targeted specific compounds to modulate the key regulating signaling pathways of cancer pathogenesis and progression. Capsaicin (alkaloid compound in chilli), catechin, epicatechin, epigallocatechin and epigallocatechin-3-gallate (phytochemicals in green tea), lutein (carotenoid found in yellow fruits), Garcinol (phenolic compound present in kokum tree) and many other naturally available compounds are also very valuable to develop the drugs to treat the cancer. An alternate repository of similar chemical diversity exists in the form of endophytic fungi inhabiting the medicinal plants. There is a high diversity of plant associated endophytic fungi in nature which are potent producers of anti-cancer compounds and offers even stronger hope for the discovery of an efficient anti-cancer drug. These fungi provide various bioactive molecules, such as terpenoids, flavonoids, alkaloids, phenolic compounds, quinines, steroids etc. exhibiting anti-cancerous property. The review discusses the relevance of phytochemicals in chemoprevention and as modulators of miRNA. The perspective advocates the imperative role of anti-cancerous secondary metabolites containing repository of endophytic fungi, as an alternative route of drug discovery.
ABSTRACT
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.
Subject(s)
Pesticides , Cross-Sectional Studies , Humans , Pilot ProjectsABSTRACT
Parasite Plasmodium falciparum is continuously giving a challenge to human beings by changing itself against most of the antimalarial drugs and its consequences can be seen in the form of a huge number of deaths each year especially in the poor and developing country. Due to its drug resistance ability, new drugs are regularly needed to kill the organism. Many new drugs have been developed based on different mechanisms. One of the potential mechanisms is to hamper protein synthesis by blocking the gene expression. S-Adenosyl-L-homocysteine (SAH) hydrolase is a NAD+ dependent tetrameric enzyme, which is responsible for the reversible hydrolysis of AdoHcy to adenosine and L-homocysteine, has been recognized as a new target for antimalarial agents since the parasite has a specific SAH hydrolase. The inhibition of SAH hydrolase causes the intracellular accumulation of S-Adenosyl-L-homocysteine, elevating the ratio of SAH to S-adenosylmethionine (SAM) and inhibiting SAM-dependent methyltransferase that catalyzes methylation of the capped structure at the 5'-terminus of mRNA, and other methylation reaction which is essential for parasite proliferation. In other words, S-Adenosyl-Lhomocysteine hydrolase regulates methyltransferase reactions. In this way, SAH hydrolase inhibitors can be used for the treatment of different diseases like malaria, cancer, viral infection, etc. by ultimately stopping the synthesis of protein. Many antiviral drugs have been synthesized and marketed which are based on the inhibition of SAH hydrolase. This review summarises the development of SAH inhibitors developed over the last 20 years and their potentiality for the treatment of malaria.
Subject(s)
Adenosylhomocysteinase/antagonists & inhibitors , Antimalarials/pharmacology , Drug Development , Enzyme Inhibitors/pharmacology , Plasmodium falciparum/drug effects , Adenosylhomocysteinase/metabolism , Antimalarials/chemical synthesis , Antimalarials/chemistry , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Molecular Structure , Parasitic Sensitivity Tests , Plasmodium falciparum/enzymologyABSTRACT
Biodegradable materials have been generating increasing bit of interest in biomedical applications and associated research. The evolution of implants made up of such materials (Mg-alloys, etc.) has the potential to be a game changer in fracture surgeries. These implants are essentially made up of a plate and a number of screws. In orthopaedic applications, they offer the biggest advantage of complete degradation after successfully supporting the fractured bone for the desired period. They may provide some nutrients that accelerate the healing process while simultaneously ensuring adequate mechanical stability. This article essentially focuses on design of a biodegradable implant plate for femoral shaft fracture, taking into consideration the dimensional accuracy of the plate, uniform biodegradation rate and adequate mechanical stability of the plate across the entire process span. The design of a biodegradable implant plate and associated specified screws that support the plate, fitted over two segments for fixation of femoral shaft fracture, has been made on the basis of femur's standard dimensions, optimized plate dimensions and uniform biodegradation rate. A confirmation regarding the safe design of the implant plate is obtained through computational structural analysis. The implant plate design turns out to be safe at specific optimized dimensions for a human being weighing 80 Kg, at corresponding loading and boundary conditions. For average monthly degradation of the plate across a period of six months, the factor of safety comes out to be more than unity. The implant plate eventually goes through complete degradation 3-6 months after the completion of the healing process and this is where the plate thickness plays a significant role.
Subject(s)
Bone Plates , Femoral Fractures , Fracture Fixation, Internal , Fracture Healing , Prosthesis Design , Femoral Fractures/surgery , Humans , Mechanical Tests , Time FactorsABSTRACT
A 26-year-old unmarried female with a history of acute abdominal pain and bleeding per vagina was brought unresponsive to the hospital. She was in shock on arrival and could not be resuscitated. Death was registered as a medico-legal case. Further investigation by the police revealed that she had amenorrhoea for eight weeks and had tested positive for pregnancy. She had consumed abortion pills purchased from a local pharmacist without consulting a doctor and had developed acute abdominal pain after 48 h. Autopsy revealed a ruptured ectopic pregnancy (tubal type).
Subject(s)
Pregnancy, Ectopic/mortality , Abdominal Pain/etiology , Adult , Autopsy/methods , Female , Humans , Pregnancy , Shock/etiology , Shock/mortalityABSTRACT
Based on the potent anticancer activity of 6'-fluorocyclopentenyl-cytosine 2b in phase IIa clinical trials for the treatment of gemcitabine-resistant pancreatic cancer, we carried out a systematic structure-activity relationship study of 6'-fluorocyclopentenyl-pyrimidines 3a-i and -purines 3j-o to discover novel anticancer agents. We also synthesized the phosphoramidate prodrug 3p of adenine derivative 1b to determine if the anticancer activity depended on the inhibition of DNA and/or RNA polymerase in cancer cells and/or on the inhibition of S-adenosylhomocysteine (SAH) hydrolase. All of the synthesized pyrimidine nucleosides exhibited much less potent anticancer activity in vitro than the cytosine derivative 2b, acting as RNA and/or DNA polymerase inhibitor, indicating that they could not be efficiently converted to their triphosphates for anticancer activity. Among all the synthesized purine nucleosides, adenine derivative 1b and N6-methyladenine derivative 3k showed potent anticancer activity, showing equipotent inhibitory activity as the positive control, neplanocin A (1a) or Ara-C. However, the phosphoramidate prodrug 3p showed less anticancer activity than 1b, indicating that it did not act as a RNA and/or DNA polymerase inhibitor like 2b. This result also demonstrates that the anticancer activity of 1b largely depends on the inhibition of histone methyltransferase, resulting from strong inhibition of SAH hydrolase. The deamination of the N6-amino group, the addition of the bulky alkyl group at the N6-amino group, or the introduction of the amino group at the C2 position almost abolished the anticancer activity.