Leg Ulceration with Infected Calcinosis Cutis Mimicking Osteomyelitis: A Case Report.

Calcified tissue exposed in a leg ulcer can become infected and develop into a nidus of infection leading to sepsis. This case details a patient with a leg wound secondary to skin biopsy. This leg ulceration did not heal due to an underlying calcified mass and led to five hospital admissions for sepsis. She was diagnosed as having calcinosis cutis, which was suspected to be the source of her infections. The calcified mass was resected, and she healed uneventfully without further infections. Calcified soft-tissue masses should be considered in nonhealing leg ulcers and ulcers with multiple recurrent infections. Radiographs can be used to diagnose this condition, and surgical excision can be considered in cases of infection.

Pregnenolone derivatives for the treatment of Alzheimer's disease: synthesis, and in vitro inhibition of amyloid ß1-42 peptide aggregation, acetylcholinesterase and carbonic anhydrase-II.

The amyloid state, which is a specific conformation of proteins, offers valuable information about both functional protein structures and the pathological assemblies associated with various diseases. One of the major hallmarks of Alzheimer's disease includes primarily the extracellular build-up of a peptide known as amyloid-ß, which has a sequence consisting of 39 to 42 amino acid residues, and the formation of intracellular neurofibrillary tangles mostly consisting of hyperphosphorylated tau protein. Drugs that are expected to reduce Aß production, prevent Aß aggregation, and promote Aß clearance are promising approaches for treating AD. Current work is focused on identifying the compounds that have balanced even mild biological activities against multiple targets instead of finding one-target compound with high potency. We synthesized pregnenolone derivatives and evaluated their potential against inhibition of eeAChE/eqBChE, hCA-II and self-mediated Aß1-42 peptide aggregation. Our synthesized derivatives 23, and 25-27 exhibited concomitant inhibition of all the tested macromolecular targets. All the active compounds were found to be BBB penetrants in the PAMPA assay. Furthermore, these selected compounds were found to be non-neurotoxic in the MTT assay on neuroblastoma SH-SY5Y cells. Docking studies support dual binding site (PAS and CAS) inhibition of AChE which showed Aß1-42 aggregation and AChE inhibition. Moreover, docking studies carried out on the 3D crystallographic structure of Aß1-42 peptide (PDB ID = 1IYT) showed significant interactions with amino acid residues Asp 23 and Lys 28, and hydrophobic interactions with the Phe19, Phe20, and Ala 30 effectively impeding the formation of ß-sheet structures.

Density functional theory, molecular docking, In vitro and In vivo anti-inflammatory investigation of lapachol isolated from Fernandoaadenophylla.

Medicinal plants are the main source of active chemical constituents responsible for curing or mitigating various ailments. To discover new, safe, and effective drug candidates the isolation and screening of natural products are essential. In the current research work, lapachol was isolated from Fernandoa adenophylla, which was evaluated for anti-inflammatory effect followed by molecular docking. The isolated compound was tested for anti-inflammatory effects using in vitro (HRBC assay) and in vivo (xylene-induced ear edema) experimental models. Various concentrations of lapachol demonstrated anti-inflammatory effects with a percent potential of 77.96 at 100 µM. Different concentrations of Lapachol demonstrated a dose-dependent anti-edematous effect with a maximum percent effect of 77.9 % at a higher dose. The histopathological study revealed that the application of xylene led to a significant increase in ear thickness, along with clear signs of ear edema and infiltration of inflammatory cells, as well as epidermal hyperplasia of the dermis when compared to the control group. However, treatment with the investigated compound showed a significant reduction in ear thickness and pathological differences comparable to those observed in the group treated with diclofenac. Density functional theory calculations are accomplished to gain insight into structural and spectroscopic properties. Geometry optimization, FMO, and MEP analyses are performed. Overall, the molecular docking results indicate that lapachol has potential as a COX inhibitor by binding to the active sites of both COX-1 and COX-2 enzymes.

Clinical outcomes of selective plantar fascia release for hallux interphalangeal joint ulcers.

BACKGROUND: Plantar hallux IPJ ulcers are common and challenging to manage, with many available treatments. One newer technique called SPFR has been used in the management of plantar forefoot ulcers. OBJECTIVE: This case series reports the clinical results of SPFR for treatment of strictly plantar hallux IPJ ulcers. MATERIALS AND METHODS: A retrospective chart review was conducted on patients that underwent SPFR procedure by a single foot and ankle surgeon from 2018 to 2023. The primary study outcome was to identify the rate and time of healing associated with SPFR for hallux IPJ ulcers. Only the initial surgery was evaluated for time of healing for the ulcer, healing rate, and complications. Subsequent surgeries were reviewed as well. Patient charts were further reviewed to determine the presence or absence of a postoperative complication. RESULTS: A total of 17 feet from 17 patients were studied. The hallux IPJ ulcers healed in an average of 3.0 months. The average follow-up time was 26.9 months. Fifteen patients (88.2%) healed after the SPFR procedure. Five patients (29.4%) developed transfer lesions, and 7 patients (41.2%) developed postoperative complications. CONCLUSIONS: The authors believe that SPFR can be utilized in the treatment of hallux IPJ ulcers if both surgeons and patients are aware of the potential complications and limitations of this procedure. Further research is warranted to evaluate the efficacy and reproducibility of these results.

Molecular docking, DFT studies, and anti-inflammatory evaluation of peshawaraquinone isolated from Fernandoa adenophylla.

In recent years, there has been growing interest in exploring natural compounds with anti-inflammatory properties for potential therapeutic applications. This study focuses on investigating the anti-inflammatory potential of peshawaraquinone (PAQ), a compound isolated from Fernandoa adenophylla, which is known for its local use in pain relief. We aim to evaluate the efficacy of peshawaraquinone in both in vitro and in vivo models and gain insights into its mode of action. In the in vitro Human red blood cell (HRBC) assay, various concentrations of peshawaraquinone were tested for their ability to inhibit the hemolysis of red blood cells, a well-established indicator of anti-inflammatory activity. The results demonstrated a maximum percent inhibition of 79.69 at a concentration of 100 µM, indicating significant anti-inflammatory potential. Furthermore, the in vivo xylene-induced ear edema model was employed to assess the compound's efficacy in reducing inflammation. Xylene was topically applied to the ear to induce edema, and peshawaraquinone was administered to evaluate its inhibitory effects. The findings revealed a substantial 74.19% reduction in ear edema, accompanied by decreased ear thickness and histopathological improvements, such as inhibited cell infiltration and epidermal hyperplasia. To gain further insights into the compound's mechanism of action, density functional theory (DFT) calculations were performed to investigate its spectroscopic characteristics and geometric properties. Additionally, docking studies were conducted on key targets involved in inflammation, including COX-1 and COX-2. In conclusion, this study showcases the significant anti-inflammatory potential of peshawaraquinone, offering promising prospects for its use as a natural anti-inflammatory agent. The results from both in vitro and in vivo models, as well as the mechanistic insights gained from computational analyses, provide a solid basis for further exploration of peshawaraquinone's therapeutic applications.Communicated by Ramaswamy H. Sarma.

Pathergy After Endovenous Ablation for Lower-Extremity Venous Disease: A Case Report of an Unexpected Complication.

A 64-year-old woman presents with wounds to her left ankle. Although her soft-tissue cultures and arterial Doppler and duplex studies were unremarkable, her venous reflux studies showed right and left small saphenous vein insufficiency. After 8 weeks of standard treatment, her wounds to the left ankle did not improve, and she developed a wound to her right anterior leg. Her left ankle wound healed 8 months after initial presentation, and her right leg wound healed in 3 months. Thereafter she underwent an endovenous ablation of her left small saphenous vein, without apparent complications. Two weeks after surgery, she developed an incision site scab that worsened and ulcerated. This case report highlights pathergy from endovenous ablation for lower-extremity venous disease.

Spontaneous Ogilvie's Syndrome in a Nonagenarian Male: A Study of a Rare Case With Literature Review.

Ogilvie's syndrome, or acute colonic pseudo-obstruction (ACPO), is an occasional disorder that occurs in hospitalized patients who have undergone major surgery. It presents with the clinical features of intestinal obstruction without any definitive intrinsic or extrinsic anatomical cause. Without prompt treatment, it can lead to life-threatening complications. The risk factors of this syndrome must be sought to prevent its occurrence. We report a rare case of idiopathic, spontaneous, and non-traumatic Ogilvie's syndrome, with old age as the only present risk factor in our case. To our best knowledge, this is the first-ever case reported in English scientific literature from Pakistan.

Synthesis of Sugar and Nucleoside Analogs and Evaluation of Their Anticancer and Analgesic Potentials.

Chemical modification of sugars and nucleosides has a long history of producing compounds with improved selectivity and efficacy. In this study, several modified sugars (2-3) and ribonucleoside analogs (4-8) have been synthesized from α-d-glucose in a total of 21 steps. The compounds were tested for peripheral anti-nociceptive characteristics in the acetic acid-induced writhing assay in mice, where compounds 2, 7, and 8 showed a significant reduction in the number of writhes by 56%, 62%, and 63%, respectively. The compounds were also tested for their cytotoxic potential against human HeLa cell line via trypan blue dye exclusion test followed by cell counting kit-8 (CCK-8) assay. Compound 6 demonstrated significant cytotoxic activity with an IC50 value of 54 µg/mL. Molecular docking simulations revealed that compounds 2, 7, and 8 had a comparable binding affinity to cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. Additionally, the bridged nucleoside analogs 7 and 8 potently inhibited adenosine kinase enzyme as well, which indicates an alternate mechanistic pathway behind their anti-nociceptive action. Cytotoxic compound 6 demonstrated strong docking with cancer drug targets human cytidine deaminase, proto-oncogene tyrosine-protein kinase Src, human thymidine kinase 1, human thymidylate synthase, and human adenosine deaminase 2. This is the first ever reporting of the synthesis and analgesic property of compound 8 and the cytotoxic potential of compound 6.

Synergistic effects of combined therapy of curcumin and Fructus Ligustri Lucidi for treatment of osteoporosis: cellular and molecular evidence of enhanced bone formation.

OBJECTIVE: The present study explored the effects of the combined herbal therapy consisting of curcumin (CUR) and Fructus Ligustri Lucidi (FLL) on aspects of bone regeneration. METHODS: Prior to analyzing the ability of this novel combined herbal therapy to promote aspects of bone regeneration, its cytotoxicity was determined using MC3T3-E1 cells (pre-osteoblast model). Cell proliferation was evaluated using phase-contrast microscopy and cell differentiation was estimated using alkaline phosphatase activity. The effect of the combined herbal therapy (CUR + FLL) was also assessed in terms of mineralization in the extracellular matrix (ECM) of cultured cells. Further, to explore the molecular mechanisms of bone formation, time-dependent expression of bone-regulating protein biomarkers was also evaluated. RESULTS: Combined herbal therapy (CUR + FLL) significantly upregulated the viability, proliferation and differentiation of MC3T3-E1 cells compared to the monotherapy of CUR or FLL. The magnitude of ECM mineralization (calcium deposition) was also higher in MC3T3-E1 cells treated with combined therapy. The time-dependent expression of bone-forming protein biomarkers revealed that the tendency of expression of these bone-regulating proteins was remarkably higher in cells treated with combined therapy. CONCLUSION: The co-administration of CUR and FLL had superior promotion of elements of bone regeneration in cultured cells, thus could be a promising alternative herbal therapy for the management of bone erosive disorders such as osteoporosis.

Hyaluronic acid, a promising skin rejuvenating biomedicine: A review of recent updates and pre-clinical and clinical investigations on cosmetic and nutricosmetic effects.

Hyaluronic acid (HA) plays multifaceted role in regulating the various biological processes such as skin repairmen, diagnosis of cancer, wound healing, tissue regeneration, anti-inflammatory, and immunomodulation. Owing to its remarkable biomedical and tissue regeneration potential, HA has been numerously employed as one of the imperative components of the cosmetic and nutricosmetic products. The present review aims to summarize and critically appraise recent developments and clinical investigations on cosmetic and nutricosmetic efficacy of HA for skin rejuvenation. A thorough analysis of the literature revealed that HA based formulations (i.e., gels, creams, intra-dermal filler injections, dermal fillers, facial fillers, autologous fat gels, lotion, serum, and implants, etc.) exhibit remarkable anti-wrinkle, anti-nasolabial fold, anti-aging, space-filling, and face rejuvenating properties. This has been achieved via soft tissue augmentation, improved skin hydration, collagen and elastin stimulation, and face volume restoration. HA, alone or in combination with lidocaine and other co-agents, showed promising efficacy in skin tightness and elasticity, face rejuvenation, improving aesthetic scores, reducing the wrinkle scars, longevity, and tear trough rejuvenation. Our critical analysis evidenced that application/administration of HA exhibits outstanding nutricosmetic efficacy and thus is warranted to be used as a prime component of cosmetic products.

Nanomedicines as emerging platform for simultaneous delivery of cancer therapeutics: new developments in overcoming drug resistance and optimizing anticancer efficacy.

Development and formulation of an efficient and safe therapeutic regimen for cancer theranostics are dynamically challenging. The use of mono-therapeutic cancer regimen is generally restricted to optimal clinical applications, on account of drug resistance and cancer heterogeneity. Combinatorial treatments can employ multi-therapeutics for synergistic anticancer efficacy whilst reducing the potency of individual moieties and diminishing the incidence of associated adverse effects. The combo-delivery of nanotherapeutics can optimize anti-tumor efficacy while reversing the incidence of drug resistance, aiming to homogenize pharmacological profile of drugs, enhance circulatory time, permit targeted drug accumulation, achieve multi-target dynamic approach, optimize target-specific drug binding and ensure sustained drug release at the target site. Numerous nanomedicines/nanotherapeutics have been developed by having dynamic physicochemical, pharmaceutical and pharmacological implications. These innovative delivery approaches have displayed specialized treatment effects, alone or in combination with conventional anticancer approaches (photodynamic therapy, radiotherapy and gene therapy), while reversing drug resistance and potential off-target effects. The current review presents a comprehensive overview of nanocarrier aided multi-drug therapies alongside recent advancements, future prospects, and the pivotal requirements for interdisciplinary research.

Efficient hepatoprotective activity of cranberry extract against CCl4-induced hepatotoxicity in Wistar albino rat model: Down-regulation of liver enzymes and strong antioxidant activity.

OBJECTIVE: To investigate the hepatoprotective efficacy of cranberry extract (CBE) against carbon tetrachloride (CCl4)-induced hepatic injury using in-vivo animal model. METHODS: The hepatoprotective efficacy of CBE (200 and 400 mg/kg) was investigated against CCl4 (4 mL/kg)-induced hepatotoxicity, elevated liver enzymes [ALT (alanine aminotransferase), AST (aspartate aminotransferase), and alkaline phosphatase (ALP)], and total protein (TP) contents in the serum. Moreover, CBE-aided antioxidant defense against hepatotoxic insult of CCl4 was measured by evaluating a number of anti-oxidative biomarkers including reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in the serum by using spectrophotometric analyses. RESULTS: Results showed that the exposure of experimental animals to CCl4 did induce significant hepatotoxicity compared to the non-induced (untreated) group. The oral administration of CBE demonstrated a significant dose-dependent alleviation in the liver enzymes (AST, ALT, and ALP), increased antioxidant defense (GSH, SOD, and CAT), and reduced MDA levels in the serum of treated animals compared to the animals without treatment. The resulting data showed that the administration of CBE decreased the serum levels of ALT, AST, and ALP compared to the CCl4-induced group. CONCLUSIONS: The resulting data evidenced that CBE exhibits promising hepatoprotective potential against the chemical induced hepatotoxicity, maintains homeostasis in liver enzymes, and can provide significant antioxidant defense against free radicals-induced oxidative stress.

Exploring recent developments to improve antioxidant, anti-inflammatory and antimicrobial efficacy of curcumin: A review of new trends and future perspectives.

Curcumin derivatives have been well-documented due to their natural antioxidant, antimicrobial and anti-inflammatory activities. Curcuminoids have also gained widespread recognition due to their wide range of other activities which include anti-infective, anti-mutagenic, anticancer, anti-coagulant, antiarthrititc, and wound healing potential. Despite of having a wide range of activities, the inherent physicochemical characteristics (poor water solubility, low bioavailability, chemical instability, photodegradation, rapid metabolism and short half-life) of curcumin derivatives limit their pharmaceutical significance. Aiming to overcome these pharmaceutical issues and improving therapeutic efficacy of curcuminoids, newer strategies have been attempted in recent years. These advanced techniques include polymeric nanoparticles, nanocomposite hydrogels, nanovesicles, nanofibers, nanohybrid scaffolds, nanoconjugates, nanostructured lipid carriers (NLCs), nanoemulsion, polymeric micelles and polymeric blend films. Incorporation of curcumin in these delivery systems has shown improved solubility, transmembrane permeability, long-term stability, improved bioavailability, longer plasma half-life, target-specific delivery, and upgraded therapeutic efficacy. In this review, a range of in vitro and in vivo studies have been critically discussed to explore the pharmaceutical significance and therapeutic viability of the advanced delivery systems to improve antioxidant, anti-inflammatory and antimicrobial efficacies of curcumin and its derivatives.

A qualitative and quantitative analysis of radiation dose and image quality of computed tomography images using adaptive statistical iterative reconstruction.

Image quality is a key issue in radiology, particularly in a clinical setting where it is important to achieve accurate diagnoses while minimizing radiation dose. Some computed tomography (CT) manufacturers have introduced algorithms that claim significant dose reduction. In this study, we assessed CT image quality produced by two reconstruction algorithms provided with GE Healthcare's Discovery 690 Elite positron emission tomography (PET) CT scanner. Image quality was measured for images obtained at various doses with both conventional filtered back-projection (FBP) and adaptive statistical iterative reconstruction (ASIR) algorithms. A stan-dard CT dose index (CTDI) phantom and a pencil ionization chamber were used to measure the CT dose at 120 kVp and an exposure of 260 mAs. Image quality was assessed using two phantoms. CT images of both phantoms were acquired at tube voltage (kV) of 120 with exposures ranging from 25 mAs to 400 mAs. Images were reconstructed using FBP and ASIR ranging from 10% to 100%, then analyzed for noise, low-contrast detectability, contrast-to-noise ratio (CNR), and modulation transfer function (MTF). Noise was 4.6 HU in water phantom images acquired at 260 mAs/FBP 120 kV and 130 mAs/50% ASIR 120 kV. The large objects (fre-quency < 7 lp/cm) retained fairly acceptable image quality at 130 mAs/50% ASIR, compared to 260 mAs/FBP. The application of ASIR for small objects (frequency >7 lp/cm) showed poor visibility compared to FBP at 260 mAs and even worse for images acquired at less than 130 mAs. ASIR blending more than 50% at low dose tends to reduce contrast of small objects (frequency >7 lp/cm). We concluded that dose reduction and ASIR should be applied with close attention if the objects to be detected or diagnosed are small (frequency > 7 lp/cm). Further investigations are required to correlate the small objects (frequency > 7 lp/cm) to patient anatomy and clinical diagnosis.