A standardized chamuangone enriched extract from Garcinia cowa Roxb. leaves shows acute and sub-acute safety.

ETHNOPHARMACOLOGICAL RELEVANCE: The safety assessment of herbal products is critical for their appropriate pharmacological applications. Garcinia cowa Roxb., commonly known as Cha-muang in Thai, has ethnopharmacological relevance for inflammation, infectious diseases, and diabetes. The leaf extracts of G. cowa have been extensively reported for their anticancer, anti-inflammatory, antimicrobial, and antioxidant effects. Notably, chamuangone is their major active constituent that contributes to various pharmacological properties. AIM OF THE STUDY: The current study aims to establish a standardized chamuangone enriched extract (CEE) and assess its acute and sub-acute toxicities in animal models. METHODOLOGY: CEE was established from G. cowa leaves using a microwave-assisted extraction (MAE), followed by fractionation and enrichment through silica gel vacuum and column chromatography. The concentration of chamuangone in the extract was quantified using a validated quantitative high-performance liquid chromatography (HPLC) method. The safety profiles of CEE were thoroughly evaluated in rodents according to the Organization for Economic Cooperation and Development (OECD) 425 and 407 guidelines. The effects on oxidative stress markers such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) levels were also evaluated in various organs. RESULTS: Based on the quantitative HPLC analysis, the CEE contained 73.0 ± 2.0% w/w of chamuangone. In the acute toxicity study, following up and down procedure the female rats were dosed with CEE at 1750 and 550 mg/kg body weight (b.w.), with CEE 1750 mg/kg b.w. was toxic, causing mortality, while CEE 550 mg/kg b.w. was deemed safe. An LD50 value was calculated according to the standard protocols, resulting in 970 mg/kg b.w. In histopathological examination, 550 mg/kg b.w. of CEE was safe in all the selected organs, while the 1750 mg/kg b.w. CEE treated rats exhibited toxic effects in histological tissues sections in the form of necrosis in the brain, cardiac muscle hypertrophy, liver inflammation, mild untoward effect in the spleen, fibrosis in the lungs, pancreatitis, pyelonephritis, and ovarian cyst. Administration of CEE at doses of 550 mg/kg b.w. (single dose) in the acute and 100 mg/kg b.w. (regularly 28-days) in the sub-acute toxicity studies significantly (p < 0.05) decreased levels of uric acid, triglycerides, and cholesterol. Importantly, the CEE (550 and 100 mg/kg b.w.) also significantly increased the levels of antioxidant enzymes (SOD, GSH, and CAT) and decreased MDA levels. Normal histopathology was observed in the sub-acute toxicity study in all treated groups. CONCLUSION: This study successfully concludes that CEE at a dose of 100 mg/kg b.w. is safe for therapeutic application or use as a chemopreventive functional food utilizing green extraction methods. However, chronic toxicity studies are further recommended to validate safety concerns over an extended period.

Stimuli-sensitive biomimetic nanoparticles for the inhibition of breast cancer recurrence and pulmonary metastasis.

Biomimetic nanoparticles represent a promising avenue for mitigating rapid clearance by the reticuloendothelial system (RES); however, current challenges include insufficient tumour targeting, suboptimal adhesion, and inadequate localized drug release within tumour regions. These shortcomings contribute to persistent contests, such as recurrence and pulmonary metastasis, even with advanced breast cancer therapies. Stimuli-sensitive drug release can furbish the membrane coated nanoparticles for their efficiency against the stated problems. To enhance the efficacy of biomimetic nanoparticles in addressing these issues, we proposed a versatile, stimuli-responsive drug delivery system by encapsulating doxorubicin (Dox) and perfluorohexane (PFH) within poly (lactic-co-glycolic acid) (PLGA) nanoparticles, subsequently coated with macrophage-derived cell membranes. Within this framework, PFH serves as the mediator for ultrasonic (US)-irradiation-triggered drug release specifically within tumour microenvironment, while the macrophage-derived cell membrane coating enhances cell adhesion, enables immune evasion, and natural tumour-homing ability. The characterization assays and in vitro evaluations yielded encouraging results, indicating enhanced targeting and release efficiencies. In vivo studies demonstrated marked inhibitory effects on both breast cancer recurrence and pulmonary metastasis. The resulting data indicate that these engineered nanoparticles have notable potential for targeted delivery and controlled release upon US irradiation, thereby offering significant therapeutic efficacy against primary breast cancer, pulmonary metastasis, and recurrent malignancies. Our findings lay the groundwork for a novel clinical approach, representing an intriguing direction for ongoing investigation by oncologists.

Albumin-coated green-synthesized zinc oxide nanoflowers inhibit skin melanoma cells growth via intra-cellular oxidative stress.

Zinc oxide (ZnO) has attracted a substantial interest in cancer research owing to their promising utility in cancer imaging and therapy. This study aimed to synthesized ZnO nanoflowers coated with albumin to actively target and the inhibit skin melanoma cells. We synthesized bovine serum albumin (BSA)-coated ZnO nanoflowers (BSA@ZnO NFs) and evaluated it's in vitro and in vivo therapeutic efficacy for skin cancer cells. BSA@ZnO NFs were prepared via single-step reduction method in the presence of plant extract (Heliotropium indicum) act as a capping agent, and further the successful fabrication was established by various physico-chemical characterizations, such as scanning electron microscopy (SEM), Fourier transform infra-red (FT-IR) spectroscopy, and x-rays diffraction (XRD) analysis. The fabricated BSA@ZnO NFs appeared flower like with multiple cone-shaped wings and average hydration size of 220.8 ± 12.6 nm. Further, BSA@ZnO NFs showed enhanced cellular uptake and cytocidal effects against skin cancer cells by inhibiting their growth via oxidative stress compared uncoated ZnO NFs. Moreover, BSA@ZnO NFs showed enhance biosafety, blood circulation time, tumor accumulation and in vivo tumor growth inhibition compared to ZnO NFs. In short, our findings suggesting BSA@ZnO NFs as a promising candidate for various types of cancer treatment along with chemotherapy.

Rationalized landscape on protein-based cancer nanomedicine: Recent progress and challenges.

The clinical advancement of protein-based nanomedicine has revolutionized medical professionals' perspectives on cancer therapy. Protein-based nanoparticles have been exploited as attractive vehicles for cancer nanomedicine due to their unique properties derived from naturally biomacromolecules with superior biocompatibility and pharmaceutical features. Furthermore, the successful translation of Abraxane™ (paclitaxel-based albumin nanoparticles) into clinical application opened a new avenue for protein-based cancer nanomedicine. In this mini-review article, we demonstrate the rational design and recent progress of protein-based nanoparticles along with their applications in cancer diagnosis and therapy from recent literature. The current challenges and hurdles that hinder clinical application of protein-based nanoparticles are highlighted. Finally, future perspectives for translating protein-based nanoparticles into clinic are identified.

pH-responsive albumin-coated biopolymeric nanoparticles with lapatinab for targeted breast cancer therapy.

One can enhance the therapeutic index of anti-cancer drugs using albumin as a tumor homing agent for targeted cancer therapy. Herein, we sought to load lapatinib (LAPA) into small albumin-coated biopolymeric (poly-lactic co-glycolic acid (PLGA)) nanoparticles (APL NPs) by an emulsification method to improve the anti-tumor efficacy of lapatinib. The prepared APL NPs exhibited a small spherical core with an average diameter of 120.5 ± 10.2 nm with a narrow particle size distribution, high drug loading capacity (LC of 9.65 ± 1.53 %), good entrapment efficiency (EE of 75.55 ± 3.25 %), enhanced colloidal stability and a pH-responsive controlled drug release profile. Their cell-uptake and cancer cell growth inhibition were significantly higher compared to free LAPA and uncoated PLGA-LAPA (UPL) NPs, most likely because aggressive breast tumor cells over-express albumin receptors and utilize albumin as nutrient source for their growth. In addition, APL NPs possessed enhanced tumor accumulation and prolonged blood residence time compared to free LAPA and UPL NPs, allowing for potent tumor growth inhibition while exhibiting excellent biosafety. In short, the current study exploited a new and simple strategy to concurrently improve the safety and efficacy of LAPA for breast cancer treatment.

Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model.

Pentazocine (PTZ), a narcotic-antagonist analgesic, has been extensively used in the treatment of initial carcinogenic or postoperative pain. Hepatic first-pass metabolism results in low oral bioavailability and high dose wastage. Herein, 10 mg (-)-Pentazocine (HPLC-grade) was incorporated to solid lipid nanoparticles (SLNs) using a double water-oil-water (w/o/w) emulsion by solvent emulsification-evaporation technique, followed by high shear homogenization to augment its oral bioavailability, considering the lymphatic uptake. The resulting SLNs were characterized for zeta potential (ZP), particle size (PS), and polydispersity index (PDI) using a zetasizer. The entrapment efficiency (EE) and loading capacity (LC) were calculated. Chemical interactions, through the identification of active functional groups, were assessed by Fourier-transformed infrared (FTIR) spectroscopy. The nature (crystallinity) of the SLNs was determined by X-ray diffractometry (XRD). The surface morphology was depicted by transmission electron microscopy (TEM). In vitro (in Caco-2 cells) and in vivo (in male Wistar rats) investigations were carried out to evaluate the PTZ release behavior and stability, as well as the cellular permeation, cytotoxicity, systemic pharmacokinetics, antinociceptive, anti-inflammatory, and antioxidative activities of PTZ-loaded SLNs, mainly compared to free PTZ (marketed conventional dosage form). The optimized PTZ-loaded SLN2 showed significantly higher in vitro cellular permeation and negligible cytotoxicity. The in vivo bioavailability and pharmacokinetics parameters (t1/2, Cmax) of the PTZ-loaded SLNs were also significantly improved, and the nociception and inflammation, following carrageenan-induced inflammatory pain, were markedly reduced. Concordantly, PTZ-loaded SLNs showed drastic reduction in the oxidative stress (e.g., malonaldehyde (MDA)) and proinflammatory cytokines (e.g., Interleukin (IL)-1ß, -6, and TNF-α). The histological features of the paw tissue following, carrageenan-induced inflammation, were significantly improved. Taken together, the results demonstrated that PTZ-loaded SLNs can improve the bioavailability of PTZ by bypassing the hepatic metabolism via the lymphatic uptake, for controlled and sustained drug delivery.

Two Promising Anti-Cancer Compounds, 2-Hydroxycinnaldehyde and 2- Benzoyloxycinnamaldehyde: Where do we stand?

Natural bioactive compounds with anti-carcinogenic activity are gaining tremendous interest in the field of oncology. Cinnamon, an aromatic condiment commonly used in tropical regions, appeared incredibly promising as an adjuvant for cancer therapy. Indeed, its whole or active parts (e.g., bark, leaf) exhibited significant anti-carcinogenic activity, which is mainly due to two cinnamaldehyde derivatives, namely 2-hydroxycinnaldehyde (HCA) and 2- benzoyloxycinnamaldehyde (BCA). In addition to their anti-cancer activity, HCA and BCA exert immunomodulatory, anti-platelets, and anti-inflammatory activities. The highly reactive α,ßunsaturated carbonyl pharmacophore, called Michael acceptor, contributes to their therapeutic effects. The molecular mechanisms underlying their anti-tumoral and anti-metastatic effects are miscellaneous, strongly suggesting that these compounds are multi-targeting compounds. Nevertheless, unravelling the exact molecular mechanisms of HCA and BCA remains a challenging matter which is necessary for optimal controlled-drug targeting delivery, safety, and efficiency. Eventually, their poor pharmacological properties (e.g., systemic bioavailability and solubility) represent a limitation and depend both on their administration route (e.g., per os, intravenously) and the nature of the formulation (e.g., free, smart nano-). This concise review focused on the potential of HCA and BCA as adjuvants in cancer. We describe their medicinal effects as well as provide an update about their molecular mechanisms reported either in-vitro, ex-vivo, or in animal models.

Breast Cancer Inhibition by Biosynthesized Titanium Dioxide Nanoparticles Is Comparable to Free Doxorubicin but Appeared Safer in BALB/c Mice.

Cancer remains a global health burden prompting affordable, target-oriented, and safe chemotherapeutic agents to reduce its incidence rate worldwide. In this study, a rapid, cost-effective, and green synthesis of titanium dioxide (TiO2) nanoparticles (NPs) has been carried out; Ex vivo and in vivoevaluation of their safety and anti-tumor efficacy compared to doxorubicin (DOX), a highly efficient breast anti-cancer agent but limited by severe cardiotoxicity in many patients.Thereby,TiO2 NPs were eco-friendly synthetized using aqueous leaf extract of the tropical medicinal shrub Zanthoxylum armatum as a reducing agent. Butanol was used as a unique template. TiO2 NPs were physically characterized by ultraviolet-visible (UV-Vis) spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscope (SEM), X-ray powder diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR) as routine state-of-the art techniques. The synthesized TiO2 NPs were then evaluated for their cytotoxicity (by MTT, FACS, and oxidative stress assays) in 4T1 breast tumor cells, and their hemocompatibility (by hemolysis assay). In vivo anti-tumor efficacy and safety of the TiO2 NPs were further assessed using subcutaneous 4T1 breast BALB/c mouse tumor model.The greenly prepared TiO2 NPs were small, spherical, and crystalline in nature. Interestingly, they were hemocompatible and elicited a strong DOX-like concentration-dependent cytotoxicity-induced apoptosis both ex vivo and in vivo (with a noticeable tumor volume reduction). The underlying molecular mechanism was, at least partially, mediated through reactive oxygen species (ROS) generation (lipid peroxidation). Unlike DOX (P < 0.05), it is important to mention that no cardiotoxicity or altered body weight were observed in both the TiO2 NPs-treated tumor-bearing mouse group and the PBS-treated mouse group (P > 0.05). Taken together, Z. armatum-derived TiO2 NPs are cost-effective, more efficient, and safer than DOX. The present findings shall prompt clinical trials using green TiO2 NPs, at least as a possible alternative modality to DOX for effective breast cancer therapy.

Escape from abluminal LRP1-mediated clearance for boosted nanoparticle brain delivery and brain metastasis treatment.

Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.

In vitro anti-leukemic assessment and sustained release behaviour of cytarabine loaded biodegradable polymer based nanoparticles.

AIMS: The study aimed to develop, characterize, and evaluate poly (ɛ-caprolactone) (PCL) based nanoparticles for the sustained release behaviour of cytarabine and to investigate the in vitro anti-cancer influence on KG-1 leukemic cell line. MATERIALS AND METHODS: Nanoprecipitation method was used for the preparation of cytarabine loaded PCL nanoparticles. The developed nanoparticles were characterized for physicochemical properties and the anti-leukemic effect on the KG-1 cell line was evaluated. KEY FINDINGS: A total number of five formulations were prepared with size range from 120.5 ± 1.18 to 341.5 ± 3.02, entrapment efficiency (41.31 ± 0.49 to 62.28 ± 0.39%), spherical morphology, negative zeta potentials, considerable particle size distribution, compatibility between the drug and excipients and thermal stability. X-ray diffraction analysis confirmed the successful incorporation of cytarabine in PCL polymer. In vitro drug release in phosphate buffer saline (pH 7.4) showed initial burst release followed by sustained release up to 48 h. The sustained release behaviour efficiently increased the toxicity of cytarabine-loaded PCL nanoparticles to KG-1 (leukemic) and MCF-7 (breast cancer) cell lines in time dependent manner with lower IC50 values than that of drug solution. The flow cytometry study revealed the better apoptotic activity of cytarabine loaded PCL nanoparticle against treated KG-1 cell line. The western blot analysis confirmed the upregulation of cleaved caspase-3 and downregulation of Bcl-2 protein. SIGNIFICANCE: The experimental results suggest that cytarabine loaded PCL nanoparticles is an efficient carrier to prevent the dose associated toxicity while providing sustained release pattern to ensure maximum anti-cancer influence.

PSMA-targeted nanoparticles for specific penetration of blood-brain tumor barrier and combined therapy of brain metastases.

Breast cancer brain metastases (BCBM) represent a major cause of morbidity and mortality among patients with breast cancer. Systemic drug therapy, which is usually effective against peripheral breast cancers, is often ineffective on BCBM due to its poor penetration through the blood-brain tumor barrier (BTB). In this study, prostate-specific membrane antigen (PSMA) with internalization function was found to be specifically up-regulated on BCBM-associated BTB while barely detectable in normal blood-brain barrier (BBB). Here, a nanotechnology approach is reported that can overcome the BTB through ACUPA (A) and cyclic TT1 (cT) co-functionalized nanoparticles (A-NPs-cT). A-NPs-cT selectively target PSMA on BTB for specific BTB crossing and specially bind with p32 for BCBM targeting. We disclosed the effectual synergism of doxorubicin (DOX) and lapatinib (LAP) for BCBM combined therapy. A-NPs-cT exhibited boosted uptake than integrin-targeting RGD-modified NPs in BTB endothelial cells and displayed about 4.57-fold stronger penetration through the BCBM-associated BTB as compared to the normal BBB. In vivo studies showed specific BTB crossing, and remission of BCBM and prolonged survival with DOX and LAP combinatorial regimen. A-NPs-cT based DOX and LAP innovative combined therapy envisioned improved therapeutic intervention for clinical management of BCBM, for which surgery is generally inapplicable and insufficient.

Radial or femoral access in primary percutaneous coronary intervention (PCI): Does the choice matters?

BACKGROUND: This study was conducted with the aim of providing a quantitative appraisal of clinical outcomes of trans-radial access for primary percutaneous coronary interventions (PCI) in patients with ST-segment evaluation myocardial infarction (STEMI). METHODS: In this study, we compared two propensity-matched cohorts of patients who underwent primary PCI via trans-radial (TRA) and trans-femoral access (TFA) in a 1:1 ratio. The profile of two cohorts was matched for gender, age, and body mass index, diabetes, hypertension, family history, and smoking. The outcomes of primary PCI were compared for the two cohorts which included all-cause in-hospital mortality, heart failure, re-infarction, cardiogenic shock, bleeding, transfusion, cerebrovascular accident, and dialysis. RESULTS: This analysis was performed on a total of 2316 patients with 1158 patients each in the TRA and TFA group. We observed significantly lower rates of mortality, 0.8% (9) vs. 3.5% (41); p < 0.001 and bleeding, 0.5% (6) vs.1.6% (19); p = 0.009 with shorter hospital stay, 1.61 ± 1.39 vs. 1.98 ± 1.5 days, in trans-radial vs. trans-femoral. However, both fluoroscopic time and contrast volume were significantly higher in the TRA as compared to TFA group 15.57 ± 8.16 vs. 12.79 ± 7.82 min; p < 0.001 and 143.22 ± 45.33 vs. 133.78 ± 45.97; p < 0.001 respectively. CONCLUSIONS: Compared with TFA access, TRA for primary PCI is safe for patients with STEMI, it was found to be associated with a significant reduction in in-hospital mortality and bleeding complications.

Comparative assessment of clinical profile and outcomes after primary percutaneous coronary intervention in young patients with single vs multivessel disease.

BACKGROUND: Even though percutaneous coronary intervention (PCI) improved the survival of patients with acute myocardial infarction, still multivessel coronary artery disease remains an important factor burdening prognosis and it is being associated with a worse prognosis compared to single-vessel disease (SVD). AIM: To compare the clinical profile and outcomes after the primary PCI in young patients with SVD vs multivessel disease (MVD). METHODS: The retrospective cohort of patients were divided into two groups: SVD and MVD group. The study population consisted of both male and female young (≤ 45 years) patients presented with ST-elevation myocardial infarction (STEMI) at the National Institute of Cardiovascular Disease, Karachi, Pakistan and undergone primary PCI from 1st July 2017 to 31st March 2018. Pre and post-procedure management of the patients was as per the guidelines and institutional protocols. RESULTS: A total of 571 patients with STEMI, ≤ 45 years were stratified into two groups by the number of vessels involved, 342 (59.9%) with SVD and 229 (40.1%) with MVD. The average age of these patients was 39.04 ± 4.86 years. A lower prevalence of hypertension and diabetes was observed in SVD as compare to MVD group (25.1% vs 38%, P < 0.01; 11.7% vs 27.5%, P < 0.001) respectively. While, smoking was more prevalent among the SVD group as compare to MVD group (36.3% vs 28.4%, P = 0.05). The high-C Lesion was observed in a significantly higher number of younger patients with MVD as compared to SVD group (48.8% vs 39.2%, P = 0.021). Post-procedure thrombolysis in myocardial infarction flow grade was found to be not associated with the number of diseased vessels with a P value of 0.426 and thrombolysis in myocardial infarction flow grade III was observed in 98% vs 96.5% of the patients is SVD vs MVD group. CONCLUSION: The MVD comprised of around 40% of the young patients presented with STEMI. Also, this study shows that diabetes and hypertension have a certain role in the pathogenesis of multivessel diseases, therefore, preventive measures for diabetes and hypertension can be effective strategies in reducing the burden of premature STEMI.

Emergency chest wall reconstruction in open pneumo-thorax from gunshot chest: A case report.

Chest trauma, penetrating or blunt is common in this era of motor vehicle accidents, violence and terrorism in South Asia. Islamabad is the capital of Pakistan but there is no dedicated chest surgery unit in any government sector hospitals. Gunshot chest, is therefore managed by general surgery team in our tertiary care setting i.e. Federal Government Polyclinic Hospital and Post Graduate Medical Institute, Islamabad. We report a case of gunshot chest with lung contusion and open pneumothorax with a chest wall defect of 10 x 15 cm. in March 2015, this young man presented in emergency department of Federal Government Polyclinic Hospital (FGPC), Post Graduate Medical Institute (PGMI) Islamabad in shock after self-inflicted point blank suicidal gunshot to his left anterolateral chest. After primary resuscitation, the patient was shifted to OR, and a left anterolateral thoracotomy performed. Lung contusion was repaired and chest drain placed. The challenging task of closing the huge chest wall defect was performed by rotating the left latissimus dorsi muscle flap. The patient was shifted to ICU and remained stable postoperatively.

Stability Studies and Characterization of Glutathione-Loaded Nanoemulsion.

Glutathione reduced (GSH) is the mother of all the antioxidants and has an antimelanogenic effect. It is extremely vulnerable to oxidation in the solution form which limits its use. The GSH in nano-oil droplets present a potential solution to this problem. The aim of this study was to formulate glutathione-loaded nanoemulsion and assess its stability studies over a 90-day testing period. To formulate GSH-loaded nanoemulsion pseudo-ternary phase diagram, it was built with various concentrations of water, liquid paraffin oil, and surfactant mixture (Tween 80 and Span 80). The oily phase was prepared by dissolving the GSH (450 mg) in liquid paraffin oil through stirring. High-energy homogenization was used to prepare the nanoemulsion. From preformulation stability studies of the 28-day testing period, nanoemulsion (NE-19) with oil and surfactant mixture ratio (1:1) of hydrophilic lipophilic balance (HLB) value 10 was selected. The samples of NE-19 and its respective base (B-19) were kept at four different storage conditions for a period of 90 days and evaluated for physical characteristics, droplet size and distribution analysis, zeta potential analysis, electrical conductivity, mobility, polydispersity, pH, phase separation, and flow analysis at different time intervals. Glutathione in nano-oil droplets with nonionic surfactants produced oil-in-water nanoemulsions that were thermodynamically stable over the 90-day testing period at different storage conditions. NE-19 was formulated having non-Newtonian flow and pseudo-plastic behavior. pH was found in the range of 5-6. Polydispersity was less than 0.3. The droplet size of fresh nanoemulsion was 96.05 nm, whereas the zeta potential was -37.1. Mobility and electrical conductivity were -2.726 µm cm/Vs and 0.0141 mS/cm, respectively. Glutathione-loaded nanoemulsions have excellent stability, promising the solution in nano-oil droplets and are suggested for in-vivo release studies for oxidative skin related diseases.

Nanosizing Noncrystalline and Porous Silica Material-Naturally Occurring Opal Shale for Systemic Tumor Targeting Drug Delivery.

Opal shale, as a naturally occurring and noncrystalline silica material with porous structure, has the potential to be a drug delivery carrier. In this study, we obtained opal shale nanoparticles (OS NPs) through the techniques of ultrasonic emulsion and differential centrifugation. The OS NPs exhibited markedly lower cytotoxicity than crystalline mesoporous silica nanoparticles. The highly porous structure and the strong adsorbability endowed OS NPs with the ability of loading and sustained release of doxorubicin (DOX). DOX-loaded OS NPs improved tumor cellular uptake and antiproliferation compared with free drug. Interestingly, OS NPs possessed strong binding with the nuclear envelope, which can be beneficial to the nucleus localization and apoptosis inducing of loaded DOX. We further demonstrated the tumor passive targeting ability, prolonged blood circulation, and enhanced antitumor effect with limited in vivo toxicity. Our results suggest that OS NPs can be applied for tumor targeting drug delivery, which may have a significant influence on the development of silica-based drug delivery system.

Central venoplasty in AV (Arteriovenous) fistula dysfunction a palliative endovascular approach.

The ultimate treatment of chronic kidney disease is renal transplant. Patients with CKD who need temporary haemodialysis have to have indwelling catheters. The catheters used are either temporary or permacath (A permacath is a piece of plastic tubing very similar to jugular catheter used for haemodialysis). The issues with these catheters are stenosis of central vein especially subclavian. Central venous stenosis leads to impairment in optimal dialysis. We report two cases of central venous stenosis in which patients presented with pain and oedema of the arm. Venogram showed totally occluded right subclavain vein and left innominate vein. Venoplasty was done which on followup showed a normalization of arm and resumption of dialysis through AV fistula. .

Outcome of primary percutaneous coronary intervention at public sector tertiary care hospital in Pakistan.

OBJECTIVES: To determine the outcome of Primary Precutaneous Coronary Intervention (PCI) in our setup and compare the results with the west. METHODS: This study was conducted at a tertiary care teaching Hospital (National Institute of Cardiovascular Diseases Karachi, Pakistan) during January 1st, 2008 to December 31st, 2008. A total of 113 patients were enrolled who came with STEMI and agreed to go for Primary PCI. We excluded the patients who had history of Thrombolytic therapy within 24 hours, presented with Non ST-elevation Myocardial Infarction (NSTEMI) and coronary angiogram revealed significant left Main or equivalent disease. All Patients received Aspirin, Clopidogrel and Platelet Glycoprotein IIB IIIA Inhibitor. After Primary PCI patients were planned to follow at one month, 3 months and 6 months. Primary end point was to document death, MI, CABG and rehospitalization. RESULTS: Out of 113 cases, 102 (90.3%) were male and 11 (9.7%) were female, Mean age was 51.2 +/- 11.7 years, 54 (47.8%) patients had Hypertension, 28 (24.8%) were Diabetics and 44 (38.9%) were Smokers. Immediate success was achieved in 111 (98.2%) cases. In hospital mortality was 5.3% (3.5% in cardiogenic shock, 1.7% in non-shock patients). Mean Door to Balloon time remained 98.4 minutes. Twelve patients were lost to follow up. Therefore at 6 months, out of 101 patients, 8 (7.9%) died, 5 (4.9%) underwent Coronary Artery Bypass Graft (CABG) surgery and 5 (4.9 %) had been re-hospitalized either for recurrent myocardial infarction or heart failure. CONCLUSION: Optimal results of primary percutaneous coronary intervention can be achieved for acute STEMI in a developing country at a tertiary care public sector hospital. The results are comparable and nearly similar to the west.

Undefeatable coronary lesion.

We report a case in which a calcification in mid left anterior descending (LAD) artery was not apparent initially on angiogram and stenting was done after inappropriate predilation resulting in underexpansion of stent. High pressure inflation, buddy wire technique, scoring and cutting balloon inflation failed to achieve the full expansion of stent.