Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death.

Pre-clinical studies from the recent past have indicated that senescent cells can negatively affect health and contribute to premature aging. Targeted eradication of these cells has been shown to improve the health of aged experimental animals, leading to a clinical interest in finding compounds that selectively eliminate senescent cells while sparing non-senescent ones. In our study, we identified a senolytic capacity of statins, which are lipid-lowering drugs prescribed to patients at high risk of cardiovascular events. Using two different models of senescence in human vascular endothelial cells (HUVECs), we found that statins preferentially eliminated senescent cells, while leaving non-senescent cells unharmed. We observed that the senolytic effect of statins could be negated with the co-administration of mevalonic acid and that statins induced cell detachment leading to anoikis-like apoptosis, as evidenced by real-time visualization of caspase-3/7 activation. Our findings suggest that statins possess a senolytic property, possibly also contributing to their described beneficial cardiovascular effects. Further studies are needed to explore the potential of short-term, high-dose statin treatment as a candidate senolytic therapy.

Analgesic effect of ketorolac as an adjuvant to bupivacaine in ultrasound-guided pectoral nerve block (I + II) for patients undergoing modified radical mastectomy: A randomized controlled clinical trial.

Background and Aims: Many drugs have been tried as adjuvant to local anesthetic in different nerve blocks. Ketorolac is one of them, but it has never been used in pectoral nerve block. In this study, we evaluated its adjuvant effect with local anesthetic on postoperative analgesia in ultrasound (US)-guided pectoral nerve (PECS) blocks. The aim was to assess the quality and the duration of analgesia by the addition of ketorolac in the PECS block. Material and Methods: 46 patients who underwent modified radical mastectomies under general anesthesia were randomized into two groups: control group, where pectoral nerve block was given with bupivacaine 0.25% only; and ketorolac group, where the block was given with bupivacaine 0.25% and ketorolac 30 mg. Results: Patients who needed postoperative supplemental analgesia were significantly less in the ketorolac group (9 vs 21 patients, P = 0.00) and that first-time analgesic requirement was significantly later in the ketorolac group (14 hrs) postoperatively compared to the control group (9 hrs) postoperatively. Conclusion: Adding ketorolac to bupivacaine in pectoral nerve block safely increases postoperative duration of analgesia.

A novel smartphone HPTLC assaying platform versus traditional densitometric method for simultaneous quantification of alfuzosin and solifenacin in their dosage forms as well as monitoring content uniformity and drug residues on the manufacturing equipment.

The large popularity and rapid technology of smartphones have opened new avenues for their integration into different analytical methodologies and drug quality monitoring as a portable, easily accessible, and user-friendly detector. Herein, a novel and portable smartphone-based high-performance thin layer chromatographic (HPTLC) approach is proposed for the simultaneous analysis of two urological drugs, alfuzosin and solifenacin, which treat benign prostatic hyperplasia accompanied by overactive bladder syndrome. First, chromatographic separation was accomplished using an ecofriendly mobile phase, then the developed plates were visualized using Dragendorff's reagent and photographed via a smartphone's rear-facing camera fixed on a fabricated two-illumination-source chamber. The intensities of the drug spots were quantified using open-source image analysis software ImageJ over the concentration ranges of 2.0 to 30.0 µg per band for both drugs with acceptable results in ICH validation parameters. To improve the method's accuracy and reproducibility, various construction and shooting key parameters were investigated and optimized. Moreover, the study was extended to compare the obtained results with those of a benchtop densitometric method using a Camag TLC Scanner 3 at 215.0 nm; the densitometric method provided an additional assessment tool for peak purity and was capable of assaying lower drug concentrations over a linearity range of 0.2-8.0 µg per band for alfuzosin and 0.1-6.0 µg per band for solifenacin. The fast, simple, reliable, green merits of the proposed HPTLC/smartphone method suggest that it is an excellent platform for assaying marketed combined capsules and assuring their content uniformity. Moreover, the high sensitivity of the densitometric method was used, for the first time, to determine the residual content of the cited drugs on manufacturing equipment surfaces for cleaning validation. Finally, the environmental impact of the developed methods was evaluated based on green analytical chemistry principles.

Synergistic Effect of Silk Sericin and Curcumin to Treat an Inflammatory Condition.

Inflammation-related diseases are recognized as the major cause of morbidity around the globe. In this study, the anti-inflammatory potential of sericin, curcumin, and their mixture was investigated in vivo and in vitro. Edema was induced via 1% carrageenan and then sericin (0.03, 0.06, 0.09 mg/ml), curcumin (1%, 2%, 3%), and their mixture doses were applied topically. The paw circumference and thickness were measured after 1-, 2-, 3-, 4-, 5-, and 6-hour post-carrageenan injection. The levels of IL-4 and IL-10 were measured from the serum. In mice fibroblast cells, sericin (20, 40, 60 µg/ml), curcumin (5, 10, 20 µM), and mixture concentrations were applied and then stimulated with lipopolysaccharide (LPS). Afterward, the cells were used for the analysis of gene expression, and the supernatant was collected for protein expression of IL-1ß, IL-4, and IL-10. Our results demonstrated that sericin and curcumin caused a dose-dependent reduction in edema, whereas the mixture-treated group reduced the paw thickness and circumference most significantly (p = .0001). Furthermore, the mixture treatment of carrageenan-inflicted group increased the levels of anti-inflammatory cytokines, IL-4 (650.87 pg/ml) and IL-10 (183.14 pg/ml), in comparison to the carrageenan control. The in vitro data revealed that among all the treatment doses, the mixture-treated group has effectively reduced the gene (1.13-fold) and protein (51.9 pg/ml) expression of IL-1ß in comparison to McCoy cells stimulated with LPS. Moreover, mixture treatment elevated the expression of IL-4 and IL-10 at genes (4.3-fold and 3.7-fold, respectively) and protein levels (169.33 and 141.83 pg/ml, respectively). The current study reports the enhanced anti-inflammatory effects of the mixture of curcumin and sericin through modulating expressions of interleukins in vitro and in vivo. Thus, natural products (curcumin and sericin)-based formulations have greater potential for clinical investigations.

A sensing platform of molecular imprinted polymer-based polyaniline/carbon paste electrodes for simultaneous potentiometric determination of alfuzosin and solifenacin in binary co-formulation and spiked plasma.

Solid contact ion-selective electrodes (ISEs) have witnessed versatile applications in pharmaceutical and biological analysis however they suffer from some limitations. Besides formation of water layer, the doped ion exchanger in sensing membrane fails to distinguish between two ionic species having relatively similar lipophilicity and carrying same charges. Those shortcomings practically hampered the simultaneous determination of alfuzosin and solifenacin in their combined pharmaceutical combination. Hence, this paper was directed to develop two carbon paste electrodes allowing their simultaneous determination based on molecular imprinted polymers (MIPs). Efforts were firstly directed to stabilize the potential signals through synthesis of polyaniline (PANI) nanoparticles with 26 nm particle size as confirmed by means of UV-spectrophotometry, Zeta-sizer and transmission electron microscope. This was followed by its doping at electrode/ion selective membrane interface leading to diminished potential drift, better Nernstian slopes and lower limit of detections. Secondly, MIPs for each drug were prepared by precipitation polymerization technique and fully characterized by Fourier-transform infrared spectroscopy, field-emission scanning electron microscope, differential scanning calorimetry, surface area analysis and rebinding studies. The prepared MIPs were then incorporated in membrane cocktail and doped over PANI layer. The graved cavities inside MIPs act as synthetic host-tailored receptors that could recognize and bind specifically to each drug. The obtained Nernstian slopes were 57.16 mV/decade for alfuzosin MIP-based sensor and 58.17 mV/decade for solifenacin MIP-based one with respective LOD values of 7.9 × 10-7 M and 8.9 × 10-8 M. Moreover, no interference was ostensibly detected from dosage form excipients, plasma constituents or degradation products/official impurities allowing quantification of alfuzosin and solifenacin in their combined capsule, spiked human plasma and in presence of their degradation products.

Fingerprinting and iso-absorptive resolution techniques for the spectrally overlapping Dutasteride and Silodosin mixture: Content uniformity testing along with greenness profile assessment.

The realm of spectrophotometric analysis has witnessed a remarkable progress in inventing faster and simpler resolution techniques for spectrally overlapping drug mixtures. Eco-friendly and progressive spectrophotometric methods were firstly developed in this work, for the simultaneous determination of Dutasteride (DUT) and Silodosin (SLD) in their newly-marketed dosage form. The proposed methods focused on the unique spectral features of this mixture including spectral extension of SLD over DUT spectrum as well as existence of iso-absorptive points. By such way, the methods were classified into two categories; the first one was "fingerprint resolution techniques" including constant extraction coupled with spectrum subtraction and ratio subtraction coupled with constant multiplication methods. The former represented a new modification to the classical constant extraction method where one divisor and lower steps were manipulated instead. The second category was "iso-absorptive resolution techniques", such as absorptivity centering, absorbance subtraction and amplitude modulation methods. Different solvents were investigated where ethanol was found to be the optimum one regarding drugs solubility, signal sensitivity and environmental, health & safety (EHS) score. Validity of the suggested methods was assessed as per ICH-guidelines and found to be linear over concentration ranges of 5.0-90.0 µg/mL for DUT and 5.0-120.0 µg/mL for SLD. The methods were successfully applied for quantifying the cited drugs in their combined dosage form and evaluating their content uniformity. Moreover, the insignificant statistical difference between the proposed methods and official HPLC ones encourages the utilization of such spectrophotometric methods as greener and faster candidates, especially in modest quality control laboratories. Methods' greenness profile was finally guaranteed through several assessment tools, namely; national environmental methods index (NEMI), analytical eco-scale, green analytical procedure index (GAPI) and analytical greenness (AGREE) metric.

Stability-Indicating Determination of Tedizolid Phosphate in the Presence of its Active Form and Possible Degradants.

Tedizolid phosphate is an antibiotic prodrug that is metabolized into tedizolid which is used against various resistant bacterial strains. In this study, tedizolid phosphate was subjected to stress degradation conditions, namely, hydrolysis (neutral, acidic and alkaline), thermal, oxidative and photolytic ones. The prodrug was stable toward thermal and photolytic stress conditions, while it showed significant degradation upon applying oxidative and hydrolytic conditions. Two suggested chromatographic methods are described for separation and determination of tedizolid phosphate from the resulted degradation products. The first method is HPLC using Waters Xselect HSS C18 (250 × 4.6 mm, 5 µm) analytical column and mobile phase composed of phosphate buffer (50 mM, pH 6.5):acetonitrile (70:30, %v/v) pumped at flow rate of 1.0 mL/min with UV-detection at 300 nm. The second method is a TLC coupled with densitometric quantitation, precoated silica TLC-plates as a stationary phase and a mobile phase of methanol:butanol:ethyl acetate:ammonia (33%, w/v) (60:20:20:10,%v/v) were used. The chromatographed plates were scanned at 300 nm. The linearity was confirmed over concentration range of 1-100 µg/mL and 1-12 µg/band for HPLC and TLC-densitometric methods, respectively. Both methods were found to be suitable for determination of tedizolid phosphate in pure form and in its pharmaceutical formulations.

Eco-Friendly Chromatographic Methods for Determination of Acemetacin and Indomethacin; Greenness Profile Assessment.

BACKGROUND: The green chemistry approach was developed for the purpose of saving the environment by using green solvents. Applying green analytical chemistry principles to traditional methods is considered a challenge. Acemetacin is a commonly used analgesic prodrug that bioactivates to indomethacin. OBJECTIVE: Developing two simple, eco-friendly chromatographic methods for simultaneous determination of acemetacin and indomethacin. METHOD: The first method is HPLC-DAD. Separation was performed on a Waters XBridge® Shield RP18 (250 × 4.6 mm, 5 µm) analytical column with ethanol-ammonium acetate buffer (50 mM, pH 3.5 ± 0.1; 60:40, v/v) as a mobile phase at a flow rate of 1 mL/min at 25 ± 0.5°C and UV detection at 254 nm. The other method is TLC coupled with densitometric quantification using pre-coated silica TLC plates and butanol-ethyl acetate (70:30, v/v) elution system. The plates were scanned at 254 nm. RESULTS: Both methods were validated according to International Conference on Harmonization guidelines. Linearity was confirmed for both over a concentration range of 1-100 µg/mL for the HPLC method and 0.2-7 µg/band for TLC-densitometric method. The methods' greenness was evaluated by the National Environmental Methods Index, Eco-Scale, Green Analytical Procedure Index metrics and Analytical GREEnness Metric Approach. CONCLUSIONS: The proposed methods were found to be suitable for determination of studied drugs in their marketed formulations and is suggested for routine analysis in quality control laboratories. HIGHLIGHTS: The developed HPLC method shortened the elution time of the analyzed drugs saving more time and money and the TLC method lowered the drugs' detection limit. HPLC and TLC methods were validated for the assay of acemetacin and indomethacin. The methods' greenness was evaluated and compared to published methods. The developed HPLC method shortened the elution time of the analyzed drugs, saving time and money and the TLC method lowered the drugs' detection limit.

Shear wave elastography of the tibial nerve in healthy subjects.

ABSTRACT: The purpose of this study is to investigate sonoelastographic features of the tibial nerve.The study included 72 tibial nerves in 36 healthy subjects. High resolution ultrasound and Shear wave elastography were used to evaluate the tibial nerve. Cross sectional area and stiffness were measured.The mean cross sectional area of the tibial nerve was 13.4 mm2. The mean shear elastic modulus of the tibial nerve in the short axis was 23.3 kPa. The mean shear elastic modulus of the tibial nerve in long axis was 26.1 kPa. The tibial nerve elastic modulus also showed no correlation with cross sectional area neither in the long axis nor short axis. Age, height, weight, and body mass index showed no correlation with tibial nerve elastic modulus in short or long axes.The elastic modulus of the tibial nerve has been determined in healthy subjects and can serve as a reference for future assessment of polyneuropathy.

Stability assessment of tamsulosin and tadalafil co-formulated in capsules by two validated chromatographic methods.

The advent of a new pharmaceutical formulation evokes the need for examining the chemical stability of their constituents and establishing proper stability-indicating methods. Herein, the stability of the newly co-formulated Tamsulosin and Tadalafil were examined under different stress conditions. The acidic degradation of Tamsulosin yielded its sulfonated derivative, while Tadalafil was susceptible to both acidic and basic degradation. Two stability-indicating chromatographic methods, namely; high-performance thin-layer chromatography and high-performance liquid chromatography, have been developed. Significant high-performance thin-layer chromatography-fractionation could be achieved by utilizing a stationary phase of silica gel 60 F254 and a mobile phase composed of ethyl acetate/toluene/methanol/ammonia (4:2:4:0.6, by volumes) with densitometric recording at 280 nm over a concentration range of 0.5-25 µg/band for both drugs. The HPLC-separation could be reached on XBridge® C18 column isocraticaly by using a mobile phase having acetonitrile/phosphate buffer, pH 6.0 (45:55, v/v) pumped at a flow rate of 1.7 mL/min and applying diode array ultraviolet-detection at 210 nm over a linearity range of 3-70 µg/mL for each drug. Specificity of the two methods was additionally assured via peak purity assessment. Moreover, the methods were distinctly exploited for evaluating the drugs' stability in accelerated stability-studied samples of Tamplus® capsules.

Microwave-enforced green synthesis of novel magnetic nano composite adsorbents based on functionalization of wood sawdust for fast removal of calcium hardness from water samples.

Developing new generation of adsorbents for water treatment to reduce calcium hardness and producing high quality water is important and continuous trend. This manuscript is devoted with this direction. Thus, two novel magnetic nanocomposite adsorbents were synthesized by covalently binding of tartaric acid (TA) and citric acid (CA) to wood sawdust coated magnetic nanoparticles (WSD@Fe3 O4 NPs) using green microwave solvent-less technique. The adsorbents thus prepared WSD@Fe3 O4 NPs-TA and WSD@Fe3 O4 NPs-CA were characterized using Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. Preliminary batch experiments were performed to evaluate percentage of Ca(II) adsorbed by the bare WSD@Fe3 O4 NPs and its functionalized forms by TA and CA, as a function of pH (initial concentration 80 mg/L), indicated 59.5%, 84.70%, and 99.29%, respectively, at pH 7 as optimal value. To attain maximum adsorption capacity, effect of adsorbent dosage and contact time were also optimized for the two modified adsorbents. Accordingly, Ca(II) adsorption capacity was determined to be 18.4 mg/g as exhibited by WSD@Fe3 O4 NPs-TA. However, WSD@Fe3 O4 NPs-CA showed higher capacity value recorded to be 27.2 mg/g. The novel adsorbents were successfully applied for fast reduction of calcium hardness from real water samples, during 15-20 min and via two consecutive in situ batch operations. PRACTITIONER POINTS: This manuscript aims to minimize Ca(II) hardness in aqueous solutions by performing magnetic separation under external magnetic field. WSD was magnetized using Fe3 O4 then modified by using safe organic modifiers using of the benefits of solvent-less microwave radiation technique for adsorbent synthesis and functionalization. Two novel environmentally magnetic nanocomposites WSD@Fe3 O4 NPs-TA and WSD@Fe3 O4 NPs-CA were checked on real water samples.

Adsorptive removal of oil spill from sea water surface using magnetic wood sawdust as a novel nano-composite synthesized via microwave approach.

Water pollution by oil is a serious environmental problem. Developing new generation of benign adsorbents satisfying several criteria required for real practical application is of great need. This work introduces an effort in this direction, by utilizing a facile synthesis of wood sawdust coated magnetite nanoparticles functionalized stearic acid (WSD@Fe3O4NPs/SA) as a novel nano composite along with its precursor WSD@Fe3O4NPs. SA was covalently bonded to the precursor by amide bond formation via the interaction with the silylating agent 3-aminopropyltrimethoxysilane (3-APTS). This mode of binding is more stronger than the conventional ester bond. Fourier transform infrared (FT-IR), X- ray powder diffraction (XRD), Scanning electron microscope (SEM) and Transmittance electron microscope (TEM) were employed for characterization and follow up the synthesis process. Application of the newly synthesized magnetic nano composite adsorbent under optimized parameters of contact time (min) and composite dosage (g) reveal high removal capacity values (g/g) evaluated to be 28.32 g/g, 5 min and 0.1 g for used motor oil removal and 41.22 g/g, 10 min and 0.1 g for crude oil. The high removal efficiency exhibited by WSD@Fe3O4NPs/SA was mainly argued to the long hydrocarbon chain of SA moiety and additional ـــ (CH2)3 ـــ groups incorporated 3-ATPS. Moreover, Analysis of the oil adsorption experimental equilibrium data were well fitted with Freundlish model with correlation coefficients r2 = 0.9788 and 0.9896 for used motor oil and crude oil, respectively. The kinetic data were correlated using two kinetic models and the results were in harmony with pseudo-second order.

Double-Track Electrochemical Green Approach for Simultaneous Dissolution Profiling of Naproxen Sodium and Diphenhydramine Hydrochloride.

Acquisition of the dissolution profiles of more than single active ingredient in a multi-analyte pharmaceutical formulation is a mandatory manufacturing practice that is dominated by utilization of the off-line separation-based chromatographic methods. This contribution adopts a new "Double-Track" approach with the ultimate goal of advancing the in-line potentiometric sensors to their most effective applicability for simultaneous acquisition of the dissolution profiles of two active ingredients in a binary pharmaceutical formulation. The unique abilities of these sensors for real-time measurements is the key driver for adoption of "green analytical chemistry" (GAC) principles aiming to expand the application of eco-friendly analytical methods With the aim of performing a side-by-side comparison, this work investigates the degree of adherence of ISEs to the 12 principles of GAC in multicomponent dissolution profiling with respect to the HPLC. For the proof of concept, a binary mixture of naproxen sodium (NAPR) and diphenhydramine hydrochloride (DIPH) marketed as Aleve pm® tablets was selected as a model for which dissolution profiles were attained by two techniques. The first "Double-Track" in-line strategy depends on dipping two highly integrated membrane sensors for continuous monitoring of the dissolution of each active pharmaceutical ingredient (API) by tracing the e.m.f change over the time scale. For the determination of NAPR, sensor I was developed using tridodecyl methyl ammonium chloride as an anion exchanger, while sensor II was developed for the determination of DIPH using potassium tetrakis (4-chlorophenyl) borate as a cation exchanger. The second off-line strategy utilizes a separation-based HPLC method via off-line tracking the increase of peak area by UV detection at 220nm over time using a mobile phase of acetonitrile: water (90:10) pH 3. The advantages of the newly introduced "Double-Track" approach regarding GAC principles are highlighted, and the merits of these benign real-time analyzers (ISEs) that can deliver equivalent analytical results as HPLC while significantly reducing solvent consumption/waste generation are described.

Stem Cell Therapy for Avascular Necrosis of Femoral Head in Sickle Cell Disease: Report of 11 Cases and Review of Literature.

BACKGROUND AND OBJECTIVE: Sickle cell disease (SCD) is quite common in eastern Saudi Arabia and Avascular necrosis of femoral head (ANFH) occurs in 30% of the young patients leading to early joint arthroplasty. This study was conducted to assess the benefits of injection of osteoblasts in the avascular lesions of the head of femur. PATIENTS AND METHODS: A preset technique was used, 10 CC of bone marrow aspiration was performed under local anesthesia and aseptic technique. Osteoblasts were separated from the bone marrow cells. The avascular area was drilled and 10 million osteoblasts were transplanted at the lesion site. Patients were seen in the out patient clinic after two weeks for removal of the suture and addressed the questionnaire and examined for the range of movement. The follow up MRI was performed at 4 months. RESULTS: The average age was 20.2±3.9 years. The mean hemoglobin S was 81.6±4.8 percent. Quality of Life Score for Chronic Hip Disease was assessed and found at 8.6 (1 being the severe limitation and 10 being normal), whereas Harris hip score improved from 41.7±5.1 to 88.93±3.6 (p < 0.001). MRI of pre and post osteoblast implantation showed robust new bone formation and disappearance of the avascular lesions. CONCLUSIONS: The short term results were good and we believe the injection of osteoblast in the avascular lesion of head of femur is a less invasive procedure devoid of any untoward complications and merits such treatment in large patient group with longer follow up.

Estimation of ultrasound reference values for the ulnar nerve fascicular number and cross-sectional area in young males: A cross-sectional study.

The objective of this study is to estimate the reference values for the number of fascicles and cross-sectional area (CSA) of the ulnar nerve at a single predetermined site by ultrasound in healthy young adult males.The demographic and physical characteristics of 50 adult male volunteers were evaluated and recorded. The subjects were positioned supine with the elbow flexed at 90° and the palm of the hand placed on a hard surface. The ulnar nerve was scanned bilaterally 1 cm proximal to the medial epicondyle in projection of the cubital tunnel. The number of fascicles and mean CSA of the ulnar nerve were identified. In addition, the side-to-side differences of the estimated reference values and their correlations with the age, weight, height, and body mass index (BMI) were evaluated.The mean fascicular number was 5.66 ±â€Š1.48, the mean ultrasound-estimated CSA of the ulnar nerve was 6.54 ±â€Š1.67 mm and both sides were comparable in the mean CSA and fascicular number (6.43 ±â€Š1.80 mm and 5.88 vs 6.64 ±â€Š1.55 mm and 5.44, for right and left side, respectively). No significant correlations were observed between CSA and fascicles number and age, weight, height, or BMI of study subjects.The reference values for the number of fascicles number and the CSA of the ulnar nerve at a single predetermined site were identified. These values could be used for the sonographic diagnosis and follow-up of the ulnar nerve lesions.

Premature senescence of endothelial cells upon chronic exposure to TNFα can be prevented by N-acetyl cysteine and plumericin.

Cellular senescence is characterized by a permanent cell-cycle arrest and a pro-inflammatory secretory phenotype, and can be induced by a variety of stimuli, including ionizing radiation, oxidative stress, and inflammation. In endothelial cells, this phenomenon might contribute to vascular disease. Plasma levels of the inflammatory cytokine tumor necrosis factor alpha (TNFα) are increased in age-related and chronic conditions such as atherosclerosis, rheumatoid arthritis, psoriasis, and Crohn's disease. Although TNFα is a known activator of the central inflammatory mediator NF-κB, and can induce the intracellular generation of reactive oxygen species (ROS), the question whether TNFα can induce senescence has not been answered conclusively. Here, we investigated the effect of prolonged TNFα exposure on the fate of endothelial cells and found that such treatment induced premature senescence. Induction of endothelial senescence was prevented by the anti-oxidant N-acetyl cysteine, as well as by plumericin and PHA-408, inhibitors of the NF-κB pathway. Our results indicated that prolonged TNFα exposure could have detrimental consequences to endothelial cells by causing senescence and, therefore, chronically increased TNFα levels might possibly contribute to the pathology of chronic inflammatory diseases by driving premature endothelial senescence.

The effect of intranasal sodium citrate on olfaction in post-infectious loss: results from a prospective, placebo-controlled trial in 49 patients.

OBJECTIVES: Free calcium plays an integral role in peripheral olfactory processing, including feedback inhibition. It has therefore been suggested that reduction of intranasal free calcium with buffer solutions such as sodium citrate may improve olfactory function in patients with smell impairment. Several previous studies have supported this hypothesis, particularly in post-infectious olfactory loss. We therefore aimed to determine whether treatment with intranasal sodium citrate improves olfactory function in patients with post-infectious impairment. DESIGN: Prospective, single-blind, placebo-controlled trial. SETTING: Interdisciplinary Smell and Taste Clinic, TU Dresden (tertiary referral centre). PARTICIPANTS: Forty-nine adult participants with post-infectious olfactory impairment (M : F = 11 : 38, mean age 58.71 ± 11.03 years). MAIN OUTCOME MEASURES: Olfactory function (odour threshold and identification) before and after treatment as determined using "Sniffin' Sticks". Patients were treated monorhinally with 1 mL sodium citrate solution. The contralateral nasal cavity was treated with 1 mL physiological sodium chloride solution, which acted as internal control. Clinical improvement was assumed where threshold or identification score increased by ≥2.5 or 3 points, respectively, or ≥5.5 points together. RESULTS: We demonstrated a statistically significant improvement in composite threshold + identification scores following treatment with sodium citrate, compared with placebo. This was true for all patients (mean improvement 0.87 ± 2.68 points, P = 0.04), and on subgroup analysis in those with hyposmia (mean improvement 1.15 ± 2.37 points, P = 0.02). However, the effect size did not reach clinical significance. CONCLUSIONS: Further basic and clinical work is required to fully delineate the effect of intranasal sodium citrate in the treatment of post-infectious olfactory loss.

Epidemiology and predictors of recurrence of Marjolin's ulcer: experience from Mansoura Universityxs.

INTRODUCTION Marjolin's ulcer (MU) is an uncommon malignancy occurring on top of old scars. Once thought to be more common in Caucasians, is now detected increasingly in Africa. METHODS This was a retrospective study of patients with MU attending a tertiary centre within Mansoura University (Egypt) from 2004 to 2015. An institutional-based registry of skin and soft-tissue malignancies in this period revealed 560 cases, from which there were 26 cases of MU. RESULTS The most common underlying cause of MU was burns (92% of patients), followed by trauma. A predilection towards males was detected. The latent period was 4-70 (median, 25) years. Recurrence occurred in 12 cases, with multiple recurrences occurring in 5 cases. MU recurrence was noted as early as 3 months and as late as 25 years after surgery. CONCLUSIONS Young patients with MU are at higher risk of recurrence and should be followed up closely. A thorough search for nodal metastasis (especially in those with high-grade tumours) should be done. Wide local excision and leaving wounds to heal by secondary intention seems to be a viable treatment option.

Stem Cell Therapy for Avascular Necrosis of Femoral Head in Sickle Cell Disease: Report of 11 Cases and Review of Literature

BACKGROUND AND OBJECTIVE: Sickle cell disease (SCD) is quite common in eastern Saudi Arabia and Avascular necrosis of femoral head (ANFH) occurs in 30% of the young patients leading to early joint arthroplasty. This study was conducted to assess the benefits of injection of osteoblasts in the avascular lesions of the head of femur. PATIENTS AND METHODS: A preset technique was used, 10 CC of bone marrow aspiration was performed under local anesthesia and aseptic technique. Osteoblasts were separated from the bone marrow cells. The avascular area was drilled and 10 million osteoblasts were transplanted at the lesion site. Patients were seen in the out patient clinic after two weeks for removal of the suture and addressed the questionnaire and examined for the range of movement. The follow up MRI was performed at 4 months. RESULTS: The average age was 20.2±3.9 years. The mean hemoglobin S was 81.6±4.8 percent. Quality of Life Score for Chronic Hip Disease was assessed and found at 8.6 (1 being the severe limitation and 10 being normal), whereas Harris hip score improved from 41.7±5.1 to 88.93±3.6 (p < 0.001). MRI of pre and post osteoblast implantation showed robust new bone formation and disappearance of the avascular lesions. CONCLUSIONS: The short term results were good and we believe the injection of osteoblast in the avascular lesion of head of femur is a less invasive procedure devoid of any untoward complications and merits such treatment in large patient group with longer follow up.

Latarjet Procedure for Anterior Shoulder Instability Due to Tramadol-Induced Seizures: A Multicenter Study.

BACKGROUND: Seizures, commonly due to epilepsy, are known to cause shoulder instability. Tramadol addiction has recently been found to induce seizures in patients who exceed the recommended dose. Because of the easy accessibility and low cost of tramadol, an increasingly alarming phenomenon of tramadol abuse has been demonstrated in recent years. PURPOSE/HYPOTHESIS: The purpose of this multicenter study was to investigate shoulder instability resulting from tramadol-induced seizure (TIS) as well as to recommended management for such shoulder instability. The hypothesis was that TIS leads to anterior shoulder dislocations with major bony defects, which favors bony reconstructive procedures as a suitable method of treatment. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This prospective case series study was conducted on 73 patients (78 shoulders) who presented with anterior shoulder dislocations and a clear history of tramadol abuse. The mean age of the patients was 26.8 years, and the mean number of dislocations was 14. The mean duration of addiction was 17 months, with a mean dose of 752 mg of tramadol hydrochloride per day. Glenoid and humeral bone loss ranged from 15% to 35% and from 15% to 40%, respectively. The mean follow-up period was 28 months. All patients underwent an open Latarjet procedure. RESULTS: Postoperative mean Rowe score and American Shoulder and Elbow Surgeons score at final follow-up (24 months) improved significantly from 20 to 84 and from 44 to 91, respectively (P < .05). The patient satisfaction rate reached 95%, and the mean period of return to work was 12.8 weeks. Five patients (9%) had postoperative seizures due to relapse of the tramadol abuse, but only 3 patients (5%) had redislocations with nonunion or breakage of the graft or hardware. CONCLUSION: Tramadol addiction has evolved as an important cause of seizures that can result in shoulder dislocation. Anterior shoulder instability with TIS occurs mainly with higher levels of addiction and results in significant humeral and/or glenoid bone defects. The Latarjet procedure is recommended for these patients, after control of addiction, and provides 95% satisfaction at midterm follow-up.