A new green fluorimetric micelle complexation approach for reduction of the consumed solvent and quantification of avapritinib in biological fluids.

Avapritinib (AVA) is the first medication authorized by the US-FDA in 2020 for the management of gastrointestinal stromal tumours (GISTs) that can't be treated by surgery. Cancer is among the most common causes of death worldwide and is the second most common cause of death after cardiovascular disease. Therefore, a quick, easy, sensitive, and straightforward fluorimetric approach was used to analyse AVA in pharmaceutical materials and blood plasma (pharmacokinetic). The suggested technique relies on 2% sodium dodecyl sulphate (SDS, pH 4) micellar system augmentation of the fluorescence of the tested drug. The technique demonstrated high relative fluorescence intensity (RFI) at 430 nm after excitation at 340 nm. Concentrations ranging from 20.0-400.0 ng mL-1 with a limit of quantitation of 9.47 ng mL-1 were used to obtain luminescence data for the studied medicine. In addition, the quantum yield of the AVA fluorescence was increased with the gradual addition of a surfactant at a concentration above its critical micellar level. This knowledge has been exploited to enhance the effectiveness of a spectrofluorometric technique for the estimation of AVA in human plasma (98.95 ± 1.22%) and uniformity tests with greenness assessments. The conditions for enhanced fluorescence were optimized and fully validated using US-FDA and International Conference on Harmonization (ICH) rules. This innovative strategy was expanded for AVA stability research in human plasma across various circumstances. This approach is an eco-friendly solution compared to traditional testing methods that use hazardous chemicals.

Integration of a facile sustainable resonance Rayleigh scattering switchable-based system for feasible determination of centrophenoxine, a nootropic and antioxidant agent; application to crude materials and dosage forms.

The proposed research adheres to a certain methodology to ensure that the technique used for analyzing the centrophenoxine drug is sustainable and green. It is important to highlight that several tools that have been recently developed were utilized as potential indicators of environmental sustainability and applicability. The present research presents a novel and entirely innovative method utilizing ultrasensitive spectrofluorimetry for the detection of centrophenoxine (CPX) drug. The employed methodology in this study involved the utilization of one-step, one-pot, and direct spectrofluorimetric technique, which was found to be both efficient and environmentally sustainable in the validation and assessment of the drug. Simply, when CPX and erythrosine B reagent were combined in an acidic environment, the highly resonance Rayleigh scattering product was immediately produced. The sensitivity limits were observed to be within the range of 15-47 ng mL-1, whereas the linearity was assessed to be in the range of 50-2000 ng mL-1. The optimal settings for all modifiable parameters of the system were ascertained through an analysis of centrophenoxine-erythrosine B complexes. Moreover, the system demonstrated compliance with International Council for Harmonization (ICH) specifications without encountering any issues. The suggested process was then rated on different recent environmental safety measuring metrics to see how good it was for the environment. Fortunately, the WAC standards that combine ecological and functional elements utilizing the Green/Red/Blue (RGB 12) design also acclaimed the current analytical technique as a white one. Additionally, a new applicability evaluation tool (BAGI) was employed to estimate the practicability of the planned method in the analytical chemistry field.

Geochemistry of Liquid Hydrocarbons and Natural Gases Combined with 1D Basin Modeling of the Oligocene Shale Source Rock System in the Offshore Nile Delta, Egypt.

The current study aims to integrate the geochemical characteristics of the Oligocene shale source rock system, oil, condensate, and natural gas samples in the Oligocene sandstone reservoirs from three exploration wells located in the offshore Nile Delta, East Mediterranean Sea, using organic geochemistry and a 1D basin modeling scheme. The Tineh shales exhibit total organic carbon values ranging between 0.90 and 1.89 wt %, along with hydrogen index values in the range of 54-240 mg hydrocarbon/g rock. The geochemical characterization suggests that the shale intervals of the Oligocene Tineh Formation contain type II-III and type III kerogens and, thereby, could be regarded as promising oil- and gas-prone source rocks with high contributions of gas generation potential. The study also reconstructs the 1D thermal and burial history models, showing that the Oligocene Tineh source rock system is in the main oil and wet gas generation phases from the late Miocene to the present time. The simulated basin models reveal the transformation (TR) of 10-50% kerogen to oil during the late Miocene-early Pliocene period and that the Oligocene Tineh source rock system has larger oil generation and expulsion competency, with a TR value of up to 65% during the early Pliocene-Pleistocene time period. The thermogenic gas was also formed during this time and continued to the present day. This study also investigated the presence of oil and condensate in the Oligocene sandstone reservoir samples and revealed that they were generated from mature source rock, ranging from moderately to highly mature stages. This source rock unit was deposited in fluvial to fluvial-deltaic environments under oxic mixed organic conditions and accumulated during the Tertiary time, as evidenced by the presence of the oleanane biomarker dating indicator. The molecular and isotope compositions of natural gases revealed that most of the natural gases in the Oligocene sandstone reservoir are mainly thermogenic methane gases that were generated from mainly mixed organic matter. The thermogenic methane gases were formed mainly from secondary cracking of oil and gas, with small contributions of primary kerogen cracking. The properties of natural gases together with oil and condensate in the Oligocene reservoir rocks suggest that most of the thermogenic methane gases and associated liquid hydrocarbons are derived primarily from the Oligocene shale source rock system and formed by primary kerogen cracking and secondary oil and oil/gas cracking in different thermal maturity stages. Therefore, the Oligocene Tineh Formation can be regarded as self-source generation and self-reservoir rock; hence, an intensive oil exploration and production program can be recommended whenever the Tineh source rock system is is well developed and deeply buried.

Application of a white and green spectrofluorimetric approach for facile quantification of amlodipine, a hypotensive drug, in batch materials, dosage forms, and biological fluids; content homogeneity testing.

The suggested study adheres to a particular protocol to ensure that the process is environmentally friendly and sustainable. It is worth mentioning that several tools have been adopted as prospective measures of the method greenness. Fortunately, the established analytical method is identified as white by the white analytical chemistry (WAC) concept, which uses the red/ green/blue color scheme (RGB 12 tool) to combine ecological and functional factors for the first time in studying of the cited drug. Amlodipine (AMD), a cardiovascular treating agent, belongs to the dihydropyridine class of oral calcium channel-blocking agents. This article presents a novel, simple, green, one-pot-processed, fast, and ultrasensitive fluorimetric approach for monitoring and assessment of AMD using molecular-size-dependent fluorescence augmentation of the light scattering-driven signal of eosin, a biological stain at a wavelength of 415 nm. This enhancement was directly proportional to the size of the produced complex. The linearity range was from 30 to 900 ng mL-1 , with corresponding sensitivity limits (detection and quantitation levels) of 9.2 and 28 ng mL-1 , respectively. The planned approach was also successfully used to track AMD content in bulk, dosage forms, and bio-fluids (human plasma and urine). The developed method's eco-friendliness was established by different eco-rating metric tools.

Design, Characterization, and Bioanalytical Applications of Green Terbium- and Nitrogen-Doped Carbon Quantum Dots as a Fluorescent Nanoprobe for Omadacycline Analysis.

Terbium- and nitrogen-doped carbon quantum dots (Tb,N@CQDs) were greenly created employing microwave synthesis from plum juice with terbium nitrate. The synthesis of Tb,N@CQDs was fast (7 min) with a high quantum yield (35.44%). Tb,N@CQDs were fully characterized using transmission electron microscopy, Zeta potential analysis, fluorescence, and ultraviolet spectroscopy. Omadacycline (OMC) is a broad-spectrum tetracycline that has been recently approved by the United States Food and Drug Act (FDA) in October 2018. OMC is the first oral aminomethylcycline class antibiotic drug that was authorized for the treatment of acute skin structure infections and community-acquired pneumonia. Tb,N@CQDs exhibited emission at 440 nm after excitation at 360 nm, where their fluorescence intensity showed a reduction upon addition of OMC. The experimental parameters were further studied and optimized. The linear range was between 40 and 60 parts per billion (ppb), with (limit of quantitation) equal to 34.78 ppb. The proposed approach was validated for bioanalytical purposes using FDA guidelines and proved to be straightforward, cheap, highly sensitive, and very selective, which can be used in clinical studies. The developed approach proved to be green using some current assessment metrics and was applied successfully for the determination of OMC in human plasma, milk, and pharmaceutical formulations as well as pharmacokinetic study.

Utility of Cilefa Pink B, a foodstuff dye as a fluoro-substrate in the devising of the first facile green Molecular-mass-Related Fluorescence Sensor for quantifying amlodipine in batched material and dosage forms; content uniformity evaluation.

This study introduces the first and unique Molecular-mass-Related Fluorescence Sensor as the first fluorimetric strategy for determining amlodipine. An environmentally friendly, single-step, and direct spectrofluorimetric approach was utilized to evaluate the analyte. In an acidic setting, combining the amlodipine medication and the fluorescent dye Cilefa Pink B generated an instantaneous ultra-fluorescent product. An increase in dye response after adding amlodipine was proportional to the molecular weight of the generated complex, as measured at 329 nm. was the idea ofthe applied fluorimetric analysis. The complexing process increased the molecular mass from 879.86 to 1288.739 g mol-1. The medication's range of 0.050-1.00 µg mL-1 is directly correlated with this molecular massenlargement. The ideal settings for the changeable parameters of the system were established through an analysis of the response of the amlodipine-Cilefa Pink B system. Furthermore, the developed sensor complied with ICH (International Council for Harmonization) standards. The sensitivity limits were 0.0139 µg mL-1 (for the detection limit, LOD) and 0.042 µg mL-1 (for the quantification limit, LOQ). Additionally, this method effectively recovered the drug in its original and therapeutic dosage forms. Finally, the proposed process's environmental impact was also assessed through different modern greenness evaluation tools.

Promising FDA-approved drugs with efflux pump inhibitory activities against clinical isolates of Staphylococcus aureus.

BACKGROUND AND OBJECTIVES: Staphylococcus aureus is an opportunistic pathogen that causes wide range of nosocomial and community-acquired infections which have spread worldwide leading to an urgent need for developing effective anti-staphylococcal agents. Efflux is an important resistance mechanism that bacteria used to fight the antimicrobial action. This study aimed to investigate the efflux mechanism in S. aureus and assess diclofenac, domperidone, glyceryl trinitrate and metformin as potential efflux pump inhibitors that can be used in combination with antibiotics for treating topical infections caused by S. aureus. MATERIALS AND METHODS: Efflux was detected qualitatively by the ethidium bromide Cart-Wheel method followed by investigating the presence of efflux genes by polymerase chain reaction. Twenty-six isolates were selected for further investigation of efflux by Cart-Wheel method in absence and presence of tested compounds followed by quantitative efflux assay. Furthermore, antibiotics minimum inhibitory concentrations in absence and presence of tested compounds were determined. The effects of tested drugs on expression levels of efflux genes norA, fexA and tetK were determined by quantitative real time-polymerase chain reaction. RESULTS: Efflux was found in 65.3% of isolates, the prevalence of norA, tetK, fexA and msrA genes were 91.7%, 77.8%, 27.8% and 6.9%. Efflux assay revealed that tested drugs had potential efflux inhibitory activities, reduced the antibiotic's MICs and significantly decreased the relative expression of efflux genes. CONCLUSION: Diclofenac sodium, domperidone and glyceryl trinitrate showed higher efflux inhibitory activities than verapamil and metformin. To our knowledge, this is the first report that shows that diclofenac sodium, glyceryl trinitrate and domperidone have efflux pump inhibitory activities against S. aureus.

A Comparison of Outcomes of Reconstruction of Palmar versus Dorsal Defects of the Thumb Using a First Dorsal Metacarpal Artery Flap with a Cutaneous Bridge Segment.

Background: The aim of this study is to compare outcomes of reconstruction of palmar versus dorsal defects of the thumb using the first dorsal metacarpal artery (FDMA) flap with a cutaneous bridge segment. Methods: All FDMA flaps done at our centre for reconstruction of traumatic thumb defects in the period from November 2017 to May 2019 were included in this study. Data with regard to the patient, the injury and the flap were recorded. The outcome measures recorded include flap survival, complications, duration of follow-up, static two-point discrimination (2-PD), cortical reorientation, paresthesia at the flap and donor site, pain at the flap and donor site, Kapandji score and aesthetic outcome. Results: The study included 11 patients with an average age of 35 years. All patients were men, and the injury involved the dominant thumb in seven patients. There were five dorsal defects and six palmar defects, and the average defect size was 7.22 sq cm. All flaps survived and there were no complications. The mean follow-up period was 15.2 months. The mean static 2-PD was 9.35 mm, cortical reorientation was complete in six patients, paresthesia score at the flap was 0.27 and at the donor site was 0.36. The visual analogue scale (VAS) pain for the flap was 1.09 and for the donor site was 1.27. The average Kapandji score was 8.64 and patients rated the aesthetic outcome of the flap at 8 and of the donor site at 7.36. There were no differences in outcomes between palmar and dorsal defects except for the aesthetic outcome of the flap that was rated better for dorsal defects. Conclusion: The FDMA flap designed with a cutaneous bridge segment provided reliable, single-stage reconstruction of dorsal and palmar thumb defects with good outcomes. Patients rated the aesthetic outcome of flaps used for dorsal reconstruction higher. Level of evidence: Level IV (Therapeutic).

Vitamin D3 potentiates the nephroprotective effects of vildagliptin-metformin combination in a rat model of metabolic syndrome.

The current study was conducted to investigate the nephroprotective effects of vildagliptin-metformin combination in an experimental model of fructose/salt-induced metabolic syndrome (MetS). A major aim was to evaluate the potential capacity of vitamin D3 to potentiate the pleiotropic nephroprotective effects of vildagliptin-metformin combination. MetS was induced in adult male Wistar rats by adding fructose (10%) to everyday drinking water and salt (3%) to the diet for 6 weeks. Along with the same concentrations of fructose/salt feeding, MetS rats were then treated orally with either vildagliptin (10 mg/kg/day)-metformin (200 mg/kg/day) combination, vitamin D3 (10 µg/kg/day), or the triple therapy for a further 6 weeks. The incidence of MetS was confirmed 6 weeks after fructose/salt consumption, when the rats exhibited significant weight gain, dyslipidemia, hyperuricemia, insulin resistance, hyperinsulinemia, and impaired glucose tolerance. At the end of the 12-week experimental period, MetS rats displayed significantly deteriorated renal function, enhanced intrarenal oxidative stress and inflammation together with exaggerated renal histopathological damages and interstitial fibrosis. The study has corroborated antioxidant, anti-inflammatory, and antifibrotic effects of vildagliptin-metformin combination, vitamin D3, and the triple collaborative therapy, conferring renoprotection in the setting of MetS. Due attention has been paid to the crucial role of dipeptidyl peptidase-4 inhibition and sirtuin-1/5' adenosine monophosphate-activated protein kinase activation as novel therapeutic targets to optimize renoprotection. The apparent potentiating effect, evoked upon coadministration of vitamin D3 with vildagliptin-metformin combination, may provide a cornerstone for further clinical investigations.

Management of Failed External Fixation by Two-Staged Internal Osteosynthesis in the Lower Limb.

OBJECTIVE: This study aims to evaluate the result of a two-stage (delayed conversion) management of nonunion after failed external fixation of the lower limb. METHODS: A case series of 25 patients (19 males and six females) enrolled in this study between February 2008 and October 2016, mean age 33.4 years (range, 22-65 years). Eight had femoral fractures, and 17 had tibial fractures. All were due to high-energy trauma and were open fractures. All cases were presented by non-union after external fixation in the lower limb long bones. All patients were managed by two stages (delayed conversion) osteosynthesis. The patients have been assessed for rate and time for union, range of motion of adjacent joints, the Modified functional outcome score of Karlstrom-Olerud, and Trauma outcomes measure score. RESULTS: The mean follow-up was 36.5 months (range 24-54 months). Twenty-two cases (88%) were fully united on an average of 5.3 months. According to the Karlstrom-Olerud scores, the final functional outcome score was excellent 12 cases, good 9 cases, accepted 2 cases, and poor in two cases. As regards the trauma outcome measure score, the mean TOM after 3 months was 26.1 (25.3-27.3), 30.4 (29.3-32.1) after 12 months, and 33.4 (32.3-40) after 24 months. CONCLUSIONS: The technique of two-stage treatment of nonunions of long bone after external fixation is a successful tool to achieve bony union. It could be a favorable option with a low risk of complications and a high level of functional outcomes.

Synthesis, antitumor, antibacterial and urease inhibitory evaluation of new piperazinyl N-4 carbamoyl functionalized ciprofloxacin derivatives.

BACKGROUND: Quinolones are well known antibacterial chemotherapeutics. Furthermore, they were reported for other activities such as anticancer and urease inhibitory potential. Modification at C7 of quinolones can direct these compounds preferentially toward target molecules. METHODS: Different derivatives of ciprofloxacin by functionalization at the piperazinyl N-4 position with arylidenehydrazinecarbonyl and saturated heterocyclic-carbonyl moieties have been synthesized and characterized using different spectral and analytical techniques. The synthesized compounds were evaluated for anticancer, antibacterial, and urease inhibitory activities. RESULTS: Among the synthesized compounds derivatives 3f and 3g experienced a potent antiproliferative activity against the breast cancer BT-549 cell line, recording growth percentages of 28.68% and 6.18%, respectively. Additionally, compound 3g revealed a remarkable antitumor potential toward the colon cancer HCT-116 cells (growth percentage 14.76%). Activity of compounds 3f and 3g against BT-549 cells was comparable to doxorubicin (IC50 = 1.84, 9.83, and 1.29 µM, respectively). Test compounds were less active than their parent drug, ciprofloxacin toward Klebsiella pneumoniae and Proteus mirabilis. However, derivative 4a showed activity better than chloramphenicol against Klebsiella pneumoniae (MIC = 100.64 and 217.08 µM, respectively). Meanwhile, many of the synthesized compounds revealed a urease inhibitory activity greater than their parent. Compound 3i was the most potent urease inhibitor with IC50 of 58.92 µM, greater than ciprofloxacin and standard inhibitor, thiourea (IC50 = 94.32 and 78.89 µM, respectively). CONCLUSION: This study provided promising derivatives as lead compounds for development of anticancer agents against breast and colon cancers, and others for optimization of urease inhibitors.

Renoprotective effects of vitamin D3 supplementation in a rat model of metabolic syndrome.

PURPOSE: The study aimed to investigate the potential nephroprotective effects of vitamin D3 in metabolic syndrome (MetS) and the molecular basis of the underlying mechanisms of its action. METHODS: MetS was induced in adult male Wistar rat s by adding fructose (10%) to every day drinking water and salt (3%) to the diet. Six weeks after fructose/salt consumption, fasting serum lipid profile and uric acid levels were determined, an oral glucose tolerance test (OGTT) was performed and kidney function was checked. MetS rats were then treated orally with vitamin D3 (10 µg/kg/day) for 6 weeks. At the end of the study period (12 weeks), the OGTT test was reperformed, anthropometrical parameters were measured, urine, blood and tissue samples were collected and the animals were euthanised. RESULTS: The incidence of MetS was confirmed 6 weeks after fructose/salt consumption, when the rats exhibited significant weight gain, dyslipidemia, hyperuricemia, insulin resistance, hyperinsulinemia and impaired glucose tolerance. After 12 weeks, MetS rats displayed markedly declined renal function alongside with extravagant renal histopathological damages and interstitial fibrosis. Furthermore, significantly enhanced renal oxidative stress and inflammation were manifested. Vitamin D3 supplementation in MetS rats significantly reversed all the above-mentioned deleterious effects. CONCLUSION: The study has indeed provided mounting evidence of the promising therapeutic potential of vitamin D3 against development and progression of MetS-induced nephropathy. A new insight has been introduced into the crucial role of dipeptidyl peptidase-4 inhibition and sirtuin-1/5'adenosine monophosphate-activated protein kinase activation in the renoprotective effects of vitamin D3.

Vitamin D3 potentiates the nephroprotective effects of metformin in a rat model of metabolic syndrome: role of AMPK/SIRT1 activation and DPP-4 inhibition.

The current study aimed to investigate the molecular mechanisms of metformin and vitamin D3-induced nephroprotection in a metabolic syndrome (MetS) rat model, evaluating the capacity of vitamin D3 to potentiate metformin action. MetS was induced by 10% fructose in drinking water and 3% salt in the diet. After 6 weeks, serum lipid profile and uric acid were measured, an oral glucose tolerance test (OGTT) was performed, and kidney function was investigated. In conjunction with the same concentrations of fructose and salt feeding, MetS rats with significant weight gain, dyslipidemia, hyperuricemia, and dysglycemia were treated orally with metformin (200 mg/kg), vitamin D3 (10 µg/kg), or both daily for 6 weeks. At the end of the study period, anthropometrical parameters were recorded, OGTT was reperformed, urine and blood samples were collected, and tissue samples were harvested at sacrifice. MetS rats showed dramatically declined renal function, enhanced intrarenal oxidative stress and inflammation, and extravagant renal histopathological damage with interstitial fibrosis. Metformin and vitamin D3 significantly reversed all the aforementioned deleterious effects in MetS rats. The study has verified the nephroprotective effects of metformin and vitamin D3 in MetS, accentuating the critical role of AMP-activated protein kinase/sirtuin-1 activation and dipeptidyl peptidase-4 inhibition. Given the synergistic effects of the combination, vitamin D3 is worth being investigated as an additional therapeutic agent for preventing MetS-induced nephropathy.

Vitamin D3 potentiates the renoprotective effects of vildagliptin in a rat model of fructose/salt-induced insulin resistance.

Insulin resistance (IR) seemingly plays a role in chronic kidney disease (CKD). The present study has elucidated the crucial interplay of oxidative stress, inflammatory, apoptotic and profibrotic signaling pathways, linking IR to CKD. The study aimed at investigating the pleiotropic nephroprotective effects of either vildagliptin or vitamin D3 in a fructose/salt-induced IR rat model, highlighting the potential molecular mechanisms underlying their action. Another interesting target was to evaluate the potential capacity of vitamin D3 to potentiate the nephroprotective effects of vildagliptin. Indeed, a state of impaired fasting glucose, IR and compensatory hyperinsulinemia, constellating with significant weight gain, atherogenic dyslipidemia and hyperuricemia was established 6 weeks after fructose/salt consumption. IR rats were then treated orally with vildagliptin (10 mg/kg/day), vitamin D3 (10 µg/kg/day) or their combination for a further 6 weeks. By the end of the 12th week, untreated IR rats displayed significantly declined renal function with parallel interwined renal oxidative stress, inflammatory, apoptotic and profibrotic changes, renal histopathological damages and markedly enhanced collagen fiber deposition. Vildagliptin and vitamin D3 reversed hyperuricemia and exerted a plethora of renal anti-oxidant, anti-inflammatory, anti-apoptotic and anti-fibrotic effects. Our study has introduced a new insight into the role of dipeptidyl peptidase-4 inhibition and silent information regulator 1/5'adenosine monophosphate-activated protein kinase activation in the nephroprotective effects of either agent, elucidating their possible crosstalk with renin angiotensin aldosterone system downregulation. Considering the superadditive renoprotective effects evoked by the combination, vitamin D3 is worth being further investigated as an additional therapeutic agent for preventing IR-induced nephropathy.

Towards anticancer fluoroquinolones: A review article.

Different studies about the anticancer potential of several medically used antibacterial fluoroquinolones have been established. Fluoroquinolone derivatives, like some anti-cancer drugs, such as doxorubicin, can achieve antitumor activity via poisoning of type II human DNA topoisomerases. Interestingly, structural features required for the anticancer activity of quinolones have been determined. Most of the chemical modifications required to convert antibacterially acting fluoroquinolones into their anticancer analogs were at position 7 and the carboxylic group at position 3. This review highlights the antitumor potential of fluoroquinolones in general and summarizes the chemical modifications carried out on fluoroquinolones to become anticancer agents. Moreover, the review gives a quick recap on metal ion chelates with fluoroquinolones and their substantial role in topoisomerase poisoning and antitumor potential improvement. Hence, it should be highly interesting for researchers attempting to design and synthesize novel anticancer fluoroquinolone candidates.

Managing of post-traumatic knee arthritis by total knee arthroplasty: case series of 15 patients and literature review.

PURPOSE: Post-traumatic arthritis is one of the leading causes of joint disability. This study aims at outlining outcomes of total knee arthroplasty in post-traumatic arthritis and technical difficulty and reviewing literature regarding this issue PATIENTS AND METHODS: We analyzed the outcome of total knee arthroplasty following post-traumatic arthritis in 15 patients with unilateral involvement. Ten had stable arthritic knees treated with posterior stabilized (PS) prosthesis, while five with unstable arthritic knees treated as follows: three with ligamentous instability managed by constrained condylar prosthesis and two with osseous deficiency, metal augmentation used together with stemmed constrained condylar prosthesis (CCK). Average follow-up 6 years, mean age 49.8 years at time of arthroplasty. Patient outcomes were evaluated on the basis of Knee Society score. RESULTS: Mean clinical knee society scores (CKSS) at latest follow-up improved from 43.6 ± 11.66 points to 77.3± points postoperatively while mean functional knee society score (FKSS) improved from 40. ± 6.3 to 76.6 ± 84 postoperatively. Patients with stable knees had a higher mean values, both clinical and functional KSS, while unstable knees were poorer. Complications occurred in three cases, one with wound dehiscence with prolonged drainage treated by antibiotics and daily dressings until the wound closed completely, one was complicated by infection and improved by serial debridement, and the third case had aseptic loosening which required revision surgery. CONCLUSION: Total knee arthroplasty for post-traumatic arthritis decreases pain and improves knee function. However; the procedure is not as simple as primary arthroplasty as it is technically demanding and requires adequate planning.

Nalbuphine could decrease the rewarding effect induced by tramadol in mice while enhancing its antinociceptive activity.

Nalbuphine, a kappa-opioid agonist and mu-opioid partial agonist, has been used as an analgesic or an adjuvant with morphine to attenuate the development of morphine dependence and rewarding effect. In this study, we investigated the effect of nalbuphine on tramadol rewarding effect and antinociception. Using the conditioned place preference (CPP) paradigm in mice, we demonstrated that co-administration of nalbuphine (7mg/kg, s.c.) with tramadol (70mg/kg, s.c.) during conditioning completely blocked the CPP induced by tramadol. Co-administration of nalbuphine blocked the increase in dopamine level in the nucleus accumbens induced by tramadol. These actions were accompanied by an increase rather than attenuation of the antinociceptive effect of tramadol. These results suggest that nalbuphine could have a great potential as a pharmacotherapy for tramadol abuse.

Ectopic mediastinal thyroid tissue with a normally located thyroid gland.

Ectopic thyroid tissue (ETT) is a rare entity and a challenging differential diagnosis. This is a report of a case of a mediastinal mass that was found to be an ectopic mediastinal thyroid tissue, in a 77-year-old woman who was admitted to our hospital for breast cancer management. The mediastinal mass was identified in the postsurgical computed tomography (CT) scan of the chest and was suspected as mediastinal lymph node metastasis. A CT-guided percutaneous transthoracic punch biopsy (CT-TPB) proved to be an adequate diagnostic tool to exclude malignancy and provide a definite diagnosis of the mediastinal mass. We find that CT-guided punch biopsy as a useful diagnostic alternative enabling histopathological specimens to be obtained from mediastinal masses and lymph nodes suspected of malignancy.

Mini-cardiopulmonary bypass impact on blood conservation strategy in coronary artery bypass grafting.

OBJECTIVE: Cardiopulmonary bypass (CPB) using a closed circuit system with minimal priming volume can be a solution to ameliorate adverse effects of CPB. We hypothesize that the use of mini-bypass in routine coronary artery bypass grafting (CABG) reduces homologous blood product use and postoperative bleeding. The study is designed to determine the differences in blood loss and transfusion requirements associated with a minimized CPB circuit vs. a standard bypass circuit. METHODS: From February 2009 to August 2009, 80 patients were prospectively randomized to undergo elective CABG. Group A included 40 patients who had the minimized bypass circuit (Medtronic Resting Heart Circuit). Group B had an equal number of patients who had the standard CPB circuit (Stockert III, SEC.BM). Laboratory parameters for hemoglobin, hematocrit and platelet count were measured at baseline after initiation of CPB and after bypass. Blood usage was controlled by study-specific protocol (transfusion for hemoglobin <8 g/dl). Records were kept for blood products. The chest and mediastinal drainage was monitored for the first 24 postoperative hours. Ventilation time, inotropic use and intensive care unit (ICU) stay was compared in both groups. RESULTS: There were no statistical differences in terms of patients' demographics. Statistically significant differences were seen in transfused red blood cells volume (1.47±1.13 units in group A vs. 2.05±1.19 in group B, P<0.05), fresh frozen plasma (2.5±1.62 unit vs. 3.55±2.58 units, P<0.001), platelets (1.95±2.95 units vs. 3.23±2.85), and postoperative drainage in 24 hours (531.62±220.12 ml vs. 729±294.9 ml, P<0.05). The hematocrit was 33±5% in group A, and 27±1% in group B. There was statistical differences seen in the mean hemoglobin level which was 10.19±0.65 g/dl in group A, and 9.4±0.68 g/dl in group B. There was statistical difference in the duration of ventilation, length of ICU stay. The requirement of inotropic support was lower in group A. CONCLUSIONS: The adoption of mini-bypass significantly reduces morbidity including donor blood usage and postoperative bleeding in routine CABG patients.

Synthesis and antimicrobial activity of novel 5-amino-4-cyano-1H-pyrazole and quinazolin-4(3H)-one derivatives.

New substituted aroylhydrazones (4a-f) were synthesized from the acid hydrazide (3) and the corresponding aldehyde or aldose. 5-Amino-4-cyano-1H-pyrazole derivatives (6a-f) were prepared by the reaction of the aroylhydrazones (4a-f) with malononitrile. The synthesized compounds were tested for antimicrobial activity against various bacteria and fungi and showed moderate to high inhibition activities. Compounds incorporating a sugar moiety as well as a pyrazolyl ring in their structure displayed the highest antimicrobial activity.