Comparison of intraocular pressure profiles during the water drinking test and the modified diurnal tension curve.

OBJECTIVES: To compare intraocular pressure (IOP) during the water drinking test (WDT) and modified diurnal tension curve (mDTC) in open-angle glaucoma (OAG) patients, using multimodal, observer-masked tonometry. METHODS: Open-angle glaucoma subjects were prospectively enroled, excluding those who had undergone glaucoma filtration or laser surgery. Two-hourly mDTC Goldmann applanation (GAT) and rebound tonometry (RT) was performed between 8:00 and 16:00, and every 15 min for 45 min after ingestion of 800mls of water. Blood pressure, heart rate, pupillometry measurements, and optical coherence tomography (AS-OCT) were also recorded. RESULTS: Forty-two subjects' right eyes were included. 48% were using topical glaucoma medication. Mean baseline IOP was 14.9 ± 4.52 mmHg, with mean visual field mean deviation (±SD) -5.05 ± 5.45 dB. Strong association was found between maximum IOP during mDTC and WDT (r = 0.90, 95% CI 0.82-0.95 p < 0.0001) with agreement (mDTC-WDT) bias -0.82 mmHg, 95% LoA -1.46 to -0.18. During the WDT, mean systolic blood pressure (±SD) increased from 140.0 ± 20.0 to 153.3 ± 24.0 mmHg (p < 0.0001), mean heart rate ( ± SD) reduced from 69.5 ± 11.3 bpm to 63.6 ± 10.0 bpm (p < 0.0001), and temporal iridocorneal angle increased from 29.2 ± 6.0° to 29.6 ± 5.2° (p = 0.04). CONCLUSION: This study presents repeated, observer-masked IOP data showing strong correlation between maximum IOP during mDTC and WDT using multimodal tonometry. This supports WDT as a meaningful alternative to mDTC when investigating diurnal IOP characteristics in clinic, with reduced time requirements and associated costs.

A Triad of Shoulder Injuries Following Cardioversion: A Case Report.

Transthoracic defibrillation and cardioversion are commonly used techniques to resuscitate a patient during acute cardiac arrhythmic events. There are numerous complications associated with these procedures. We report a previously unreported complication where a patient suffered from a supraspinatus tear after cardioversion for ventricular tachycardia. There are numerous complications associated with these procedures. We report a previously unreported complication where a middle-aged Chinese patient with no previous trauma history suffered from a supraspinatus tear after cardioversion for ventricular tachycardia.

Interpositional Arthroplasty With Quadriceps Tendon in Patellofemoral Joint Osteoarthritis: An Alternative Way.

We present a case report of a 45-year-old Malay female prison officer with a diagnosis of lateral patellofemoral joint (PFJ) osteoarthritis (OA) in her right knee for whom conservative treatment failed. She was periodically followed up for the unresolving anterior right knee pain, and the patient was offered interpositional PFJ arthroplasty with the quadriceps tendon. A novel technique of interpositional PFJ arthroplasty using lateral inner section ipsilateral quadriceps tendon was applied. The approach and surgical technique were described in this case report. The aim of this study is to describe why this technique was chosen, step by step with images on how interpositional PFJ arthroplasty is done and its satisfactory outcome following a three-month follow up.

A Rare Occurrence of Opportunistic Infection by Streptococcus mitis Due to Antibiotic-Induced Neutropenia in Prosthetic Joint Infection.

Prosthetic joint infection (PJI) is a devastating complication in arthroplasty surgery. Although the prevalence is less than 2%, its functional and financial implications are significant. Part of its treatment involves the usage of prolonged and high-dose systemic antibiotics. Ironically, this predisposes the patient to unwanted adverse effects caused by the drugs. We report a case of cefazolin-induced neutropenia that led to Streptococcus mitis (S. mitis) bacteraemia in a patient with Staphylococcus aureus PJI. There have been no previous reports on cefazolin-induced neutropenic bacteraemia complicating the treatment of PJI. This case report aims to create awareness among the attending physicians on the possibility of cefazolin-induced neutropenia, which led to bacteraemia from an opportunistic microorganism. The reversal was as simple as cessation of the antibiotic itself. However, if not recognized, it could be fatal.

A Reshaping Recovery: The Reverse Shoulder Arthroplasty Triumphs in Salvaging Chronic Four-Part Proximal Humerus Fractures.

The aging population is witnessing a steady increase in the incidence of displaced proximal humerus fractures, particularly among elderly patients. Such fractures pose a significant challenge to orthopedic surgeons, given the complex interplay of factors involved, including fracture displacement, comminution, compromised bone quality, and the presence of concurrent medical comorbidities. While open reduction internal fixation (ORIF) remains a viable treatment option for these fractures, it is a technically demanding procedure associated with a high incidence of complications. Recently, reverse total shoulder arthroplasty (RTSA) with tuberosity repair has gained popularity as a successful approach for addressing such fractures. The present case report details a unique and complex case of a chronic four-part proximal humerus fracture, complicated by avascular necrosis of the humeral head, fracture non-union, and hardware penetration. The patient was successfully treated through a reverse shoulder arthroplasty procedure, highlighting the effectiveness of this surgical approach in such challenging scenarios. The advantages of RTSA in this context include the potential to address avascular necrosis, non-union, and hardware complications, as seen in our patient. Additionally, the procedure can restore functional independence and improve the overall quality of life in these challenging cases.

A study on green synthesis, characterization of chromium oxide nanoparticles and their enzyme inhibitory potential.

The conventional chemical methods of nanoparticles synthesis have been effectively replaced by nanoparticle synthesis mediated by plants. The current study describes the environmental friendly synthesis of chromium oxide nanoparticles (Cr2O3 NPs) using Erythrophleum guineense plant extract. The synthesis of Cr2O3 NPs was validated by UV/VIS spectroscopy, Energy Dispersive X-Ray (EDX), Scanning Electron Microscopy (SEM), and X-ray diffraction (XRD) studies. The appearance of the Sharpe peak at 460 nm in the UV/Vis spectrum and the colour change caused by surface plasma resonance confirmed the formation of Cr2O3 NPs. The EDX spectrum of Cr2O3 nanoparticles revealed the presence of carbon, oxygen, and chromium, while SEM analysis revealed an irregular round morphology (with a size below 400 nm). In addition, XRD studies suggested their crystalline nature by the characteristic peaks at 34° and 36° and 42° (2Ɵ), respectively. The green synthesized Cr2O3 NPs showed promise as in-vitro cholinesterase inhibitor at tested concentrations (62.5-1,000 µg/ml), with IC50 values of 120 and 100 µg/ml against Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE), respectively. The results suggested that the green synthesized Cr2O3 NPs could be used in the future to stop enzyme from working and for other biological activities.

Isolation, crystal structure, DFT calculation and molecular docking of uncinatine-A isolated from Delphinium uncinatum.

The main objective of our present research work was to explore molecular insight for potentially active new acetylcholinesterase inhibitor from the aerial parts of Delphinium uncinatum. New norditerpenoid alkaloids, uncinatine-A, was isolated from the basic alkaloidal fraction of D. uncinatum, based on bioactivity guided isolation. The structure of uncinatine-A was determined through latest spectroscopic techniques including single X-Ray diffraction technique. The structural data and electronic properties of uncinatine-A was also calculated by Density Functional Theory (DFT) using B3LYP/6-31þ G (p) basis set. The isolated natural product was evaluated for their acetyl cholinesterase inhibitory potential in dose dependent protocol (62.5-1000 µg/mL), followed by molecular docking studies. Significant competitive type inhibition activity (IC50 = 207.73 ± 0.3) was shown by isolated natural norditerpenoid against cholinesterase targets in comparison with standard drugs available in the market such as galanthamine. The molecular docking results showed that isolated natural product was well accommodated by AChE in the active site with docking scores -11.0326. This is the first report indicating uncinatine-A as a potent acetylcholinesterase inhibitor and can be used as a target drug in cerebral dementia and Alzheimer diseases.

In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from Delphinium chitralense.

This study reports the isolation of three new C20 diterpenoid alkaloids, Chitralinine A-C (1-3) from the aerial parts of Delphinium chitralense. Their structures were established on the basis of latest spectral techniques and single crystal X-rays crystallographic studies of chitralinine A described basic skeleton of these compounds. All the isolated Compounds (1-3) showed strong, competitive type inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in comparison to standard allanzanthane and galanthamine however, chitralinine-C remained the most potent with IC50 value of 11.64 ± 0.08 µM against AChE, and 24.31 ± 0.33 µM against BChE, respectively. The molecular docking reflected a binding free energy of -16.400 K Cal-mol-1 for chitralinine-C, having strong interactions with active site residues, TYR334, ASP72, SER122, and SER200. The overall findings suggest that these new diterpenoid alkaloids could serve as lead drugs against dementia-related diseases including Alzheimer's disease.

Apical lung mass-A rare presentation of multiple myeloma.

Multiple myeloma is a neoplastic proliferation of immunoglobulin-producing plasma cells with clinical features resulting from infiltration of plasma cells into bones and other organs. Multiple myeloma manifesting as an apical lung mass is less common and very few cases have been reported. We report the case of a 50-year-old female who presented with an apical lung mass which happened to be multiple myeloma arising from the upper ribs into the lung. At the time of diagnosis, patient had axillary lymph node metastasis with extensive bony involvement. This case report and literature review provides insight to a rare but significant presentation of multiple myeloma and highlights the need to consider multiple myeloma as a possible differential for Pancoast tumor in the appropriate clinical setting as this could potentially affect management options and patient outcome.

Attenuation of Scopolamine-Induced Amnesia via Cholinergic Modulation in Mice by Synthetic Curcumin Analogs.

Alzheimer's disease is an emerging health disorder associated with cognitive decline and memory loss. In this study, six curcumin analogs (1a−1f) were synthesized and screened for in vitro cholinesterase inhibitory potential. On the basis of promising results, they were further investigated for in vivo analysis using elevated plus maze (EPM), Y-maze, and novel object recognition (NOR) behavioral models. The binding mode of the synthesized compounds with the active sites of cholinesterases, and the involvement of the cholinergic system in brain hippocampus was determined. The synthesized curcumin analog 1d (p < 0.001, n = 6), and 1c (p < 0.01, n = 6) showed promising results by decreasing retention time in EPM, significantly increasing % SAP in Y-maze, while significantly (p < 0.001) enhancing the % discrimination index (DI) and the time exploring the novel objects in NORT mice behavioral models. A molecular docking study using MOE software was used for validation of the inhibition of cholinesterase(s). It has been indicated from the current research work that the synthesized curcumin analogs enhanced memory functions in mice models and could be used as valuable therapeutic molecules against neurodegenerative disorders. To determine their exact mechanism of action, further studies are suggested.

Phytochemical investigation of Hyoscyamus albus.

The work presented in this paper illustrates the isolation and structure elucidation of secondary metabolites of Hyoscyamus albus. Two new natural source and three known compounds were isolated from the Hyoscyamus albus. Among the isolated compounds, grivilloside H (1) and betulaplatoside (2) were isolated for the first time while scopolamine (3), ß-sitosterol (4) and stigmasterol (5) have been reported previously from the same plant. The structures of all the isolated compounds were established by using modern spectroscopic technique (UV, IR, NMR, and EI-MS) and by comparing with those available in literature.

Norditerpenoid alkaloids of Delphinium denudatum as cholinesterase inhibitors.

Three new norditerpenoids alkaloids, 1ß-hydroxy,14ß-acetyl condelphine (1), jadwarine-A (2), jadwarine-B (3) along with two known alkaloids isotalatizidine hydrate (4) and dihydropentagynine (5) were isolated from medicinal plant Delphinium denudatum. The structures of natural products 1-5 were established on the basis of HR-EIMS, 1H and 13C NMR (1D & 2D) spectroscopic data as well as by comparison from literature data. The structures of compound 1 and 4 were also confirmed by single crystal X-ray diffraction studies. In-vitro AChE and BChE enzyme inhibitory activities of compounds 1-5 and molecular docking studies were performed to investigate the possible molecular inhibitory mechanism of the isolated natural products. Compound 2, 4 and 5 showed competitive inhibitory effects by inhibiting AChE and BChE, respectively, while 1 and 3 showed non-competitive inhibition. This work is the first report that provides a supporting evidence about the use of constituents of Delphinium denudatum in cerebral dementia and Alzheimer diseases.

Selective dual cholinesterase inhibitors from Aconitum laeve.

New lycoctonine-type dual cholinesterase inhibitor, swatinine-C (1), along with three known norditerpenoid alkaloids, hohenackerine (2), aconorine (5) and lappaconitine (6) and two synthetically known but phytochemically new benzene derivatives, methyl 2-acetamidobenzoate (3) and methyl 4-[2-(methoxycarbonyl)anilino]-4-oxobutanoate (4), was isolated from the roots of A. laeve. Structures of new and known compounds (1-6) were established on the basis of latest spectroscopic techniques and by close comparison with the data available in literature. In vitro, compounds (1-6) were tested against AChE and BChE inhibitory activities. Compounds 1 and 2 showed competitive inhibition against AChE (IC50 = 3.7 µM, 4.53 µM) and BChE (IC50 = 12.23 µM, 9.94 µM), respectively. Compounds 5 and 6 showed promising noncompetitive type of inhibitory profile against AChE (IC50 = 2.51 and 6.13 µM) only. Compounds 3 and 4 showed weak inhibitory profile against both AChE and BChE.

Antioxidant and anticholinesterase potential of diterpenoid alkaloids from Aconitum heterophyllum.

Extensive chromatographic separations performed on the basic (pH=8-10) chloroform soluble fraction of Aconitum heterophyllum resulted in the isolation of three new diterpenoid alkaloids, 6ß-Methoxy, 9ß-dihydroxylheteratisine (1), 1α,11,13ß-trihydroxylhetisine (2), 6,15ß-dihydroxylhetisine (3), and the known compounds iso-atisine (4), heteratisine (5), hetisinone (6), 19-epi-isoatisine (7), and atidine (8). Structures of the isolated compounds were established by means of mass and NMR spectroscopy as well as single crystal X-ray crystallography. Compounds 1-8 were screened for their antioxidant and enzyme inhibition activities followed by in silico studies to find out the possible inhibitory mechanism of the tested compounds. This work is the first report demonstrating significant antioxidant and anticholinesterase potentials of diterpenoid alkaloids isolated from a natural source.

Isolation, crystal structure determination and cholinesterase inhibitory potential of isotalatizidine hydrate from Delphinium denudatum.

CONTEXT: Delphinium denudatum Wall (Ranunculaceae) is a rich source of diterpenoid alkaloids and is widely used for the treatment of various neurological disorders such as epilepsy, sciatica and Alzheimer's disease. OBJECTIVE: The present study describes crystal structure determination and cholinesterase inhibitory potential of isotalatazidine hydrate isolated from the aerial part of Delphinium denudatum. MATERIALS AND METHODS: Phytochemical investigation of Delphinium denudatum resulted in the isolation of isotalatazidine hydrate in crystalline form. The molecular structure of the isolated compound was established by X-ray diffraction. The structural data (bond length and angles) of the compound were calculated by Density Functional Theory (DFT) using B3LYP/6-31 + G (p) basis set. The cholinesterase inhibitory potential of the isolated natural product was determined at various concentrations (62.5, 125, 250, 500 and 1000 µg/mL) followed by molecular docking to investigate the possible inhibitory mechanism of isotalatazidine hydrate. RESULTS: The compound crystallized in hexagonal unit cell with space group P65. Some other electronic properties such as energies associated with HOMO-LUMO, band gaps, global hardness, global electrophilicity, electron affinity and ionization potential were also calculated by means of B3LYP/6-31 + G (p) basis set. The compound showed competitive type inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 12.13 µM and 21.41 µM, respectively. DISCUSSION AND CONCLUSION: These results suggest that isotalatazidine hydrate is a potent dual cholinesterase inhibitor and can be used as a target drug in Alzheimer diseases. This is first report indicating isotalatazidine hydrate with anticholinesterase potential.

Antimicrobial activities of Conyzolide and Conyzoflavone from Conyza canadensis.

Antibacterial and antifungal activities of the two isolated compounds from Conyza canadensis have been reported in the current study. The two isolated compounds i.e. Conyzolide (1) and Conyzoflavone (2) were tested against six bacterial and five fungal strains, employing hole diffusion and macrodilution methods. Both the compounds showed significant activities against the tested pathogens with special reference to E. coli, P. aeruginosa, S. aureus, Trichophytom longifusus, C. albicans, and C. glaberata. Conyzolide revealed comparatively better antibacterial activity against E. coli (minimum inhibitory concentration (MIC): 25 µg/mL) in comparison to Conyzoflavone. However, in case of antifungal activities, Conyzoflavone exhibited superior antifungal activity against C. albicans (MIC: 10 µg/mL) as compared to Conyzolide.

Structural insights to investigate Conypododiol as a dual cholinesterase inhibitor from Asparagus adscendens.

The main aim of the current study was to explore molecular insights for potentially new dual cholinesterase inhibitor(s) from Asparagus adscendens via molecular docking. This medicinal plant is traditionally used as a nerve tonic and remedy for memory impairments. Conypododiol was isolated from the chloroform fraction of methanolic extract of A. adscendens, based on bioactivity guided isolation. Conypododiol exhibited significant inhibition of both acetylcholinesterase and butyrylcholinesterase, having the IC(50) values 2.17 ± 0.1 µM and 11.21 ± 0.1 µM, respectively. IC(50) values of the standard compound Galanthamine for both the enzymes were 0.537 ± 0.018 µM and 8.6 ± 0.27 µM, respectively. Based on MTT cytotoxicity assay, Conypododiol was found safe against LCMK-2 monkey kidney epithelial cells and mice hepatocytes. Molecular docking studies revealed the hydrogen bonding interactions of Conypododiol with His440 and Ser200 at esteratic site (ES), and also with Tyr334 at peripheral anionic site (PAS) of the aromatic gorge of acetylcholinesterase. Simultaneous contacts of Conypododiol with PAS and ES shows its significance as a bivalent ligand. This preliminary study highlighted the potential of Conypododiol to be further developed and modified as new lead compound identified by its folk use.