Efficacy of using adipose-derived stem cells and PRP on regeneration of 40 -mm long sciatic nerve defect bridged by polyglycolic-polypropylene mesh in canine model.

BACKGROUND: Sciatic nerve repair becomes a focus of research in neurological aspect to restore the normal physical ability of the animal to stand and walk. Tissue engineered nerve grafts (TENGs) provide a promising alternative therapy for regeneration of large gap defects. The present study investigates the regenerative capacity of PRP, ADSCs, and PRP mixed ADSCs on a long sciatic nerve defect (40-mm) bridged by a polyglycolic polypropylene (PGA-PRL) mesh which acts as a neural scaffold. MATERIALS AND METHODS: The study was conducted on 12 adult male mongrel dogs that were randomly divided into 4 groups: Group I (scaffold group); where the sciatic defect was bridged by a (PGA-PRL) mesh only while the mesh was injected with ADSCs in Group II (ADSCs group), PRP in Group III (PRP group). Mixture of PRP and ADSCs was allocated in Group IV (PRP + ADSCs group). Monthly, all animals were monitored for improvement in their gait and a numerical lameness score was recorded for all groups. 6 months-post surgery, the structural and functional recovery of sciatic nerve was evaluated electrophysiologically, and on the level of gene expression, and both sciatic nerve and the gastrocnemius muscle were evaluated morphometrically, histopathologically. RESULTS: Numerical lameness score showed improvement in the motor activities of both Group II and Group III followed by Group IV and the scaffold group showed mild improvement even after 6 months. Histopathologically, all treated groups showed axonal sprouting and numerous regenerated fascicles with obvious angiogenesis in proximal cut, and distal portion where Group IV exhibited a significant remyelination with the MCOOL technique. The regenerative ratio of gastrocnemius muscle was 23.81%, 56.68%, 52.06% and 40.69% for Group I, II, III and IV; respectively. The expression of NGF showed significant up regulation in the proximal portion for both Group III and Group IV (P ≤ 0.0001) while Group II showed no significant difference. PDGF-A, and VEGF expressions were up-regulated in Group II, III, and IV whereas Group I showed significant down-regulation for NGF, PDGF-A, and VEGF (P ≤ 0.0001). CONCLUSION: ADSCs have a great role in restoring the damaged nerve fibers by secreting several types of growth factors like NGF that have a proliferative effect on Schwann cells and their migration. In addition, PRP therapy potentiates the effect of ADSCs by synthesis another growth factors such as PDGF-A, VEGF, NGF for better healing of large sciatic gap defects.

Platelet-rich plasma attenuates the UPEC-induced cystitis via inhibiting MMP-2,9 activities and downregulation of NGF and VEGF in Canis Lupus Familiaris model.

One of the most prevalent disorders of the urinary system is urinary tract infection, which is mostly brought on by uropathogenic Escherichia coli (UPEC). The objective of this study was to evaluate the regenerative therapeutic and antibacterial efficacy of PRP for induced bacterial cystitis in dogs in comparison to conventional antibiotics. 25 healthy male mongrel dogs were divided into 5 groups (n = 5). Control negative group that received neither induced infection nor treatments. 20 dogs were randomized into 4 groups after two weeks of induction of UPEC cystitis into; Group 1 (control positive; G1) received weekly intravesicular instillation of sodium chloride 0.9%. Group 2 (syst/PRP; G2), treated with both systemic intramuscular antibiotic and weekly intravesicular instillation of PRP; Group 3 (PRP; G3), treated with weekly intravesicular instillation of PRP, and Group 4 (syst; G4) treated with an intramuscular systemic antibiotic. Animals were subjected to weekly clinical, ultrasonographic evaluation, urinary microbiological analysis, and redox status biomarkers estimation. Urinary matrix metalloproteinases (MMP-2, MMP-9) and urinary gene expression for platelet-derived growth factor -B (PDGF-B), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) were measured. At the end of the study, dogs were euthanized, and the bladder tissues were examined macroscopically, histologically, and immunohistochemically for NF-κB P65 and Cox-2. The PRP-treated group showed significant improvement for all the clinical, Doppler parameters, and the urinary redox status (p < 0.05). The urinary MMPs activity was significantly decreased in the PRP-treated group and the expression level of urinary NGF and VEGF were downregulated while PDGFB was significantly upregulated (p < 0.05). Meanwhile, the urinary viable cell count was significantly reduced in all treatments (P < 0.05). Gross examination of bladder tissue showed marked improvement for the PRP-treated group, expressed in the histopathological findings. Immunohistochemical analysis revealed a marked increase in Cox-2 and NF-κB P65 in the PRP-treated group (P < 0.05). autologous CaCl2-activated PRP was able to overcome the bacterial infection, generating an inflammatory environment to overcome the old one and initiate tissue healing. Hence, PRP is a promising alternative therapeutic for UPEC cystitis instead of conventional antibiotics.

Regorafenib: A comprehensive drug profile.

Regorafenib is a small molecule tyrosine kinase inhibitor administered orally drug, act by inhibiting the activity of the VEGF receptors. It is used for the treatment of patients with metastatic colorectal cancer (CRC), advanced gastrointestinal stromal tumors, and hepatocellular carcinoma. This comprehensive profile on regorafenib includes an original data as well as data collected from the literature on Profiles of Methods of Drug Synthesis, different Physical Drug Profiles, Drug Analytical methods and Pharmacological profile (ADME). This chapter is divided into five main sections: General Description of the drug, Physical Characteristics, Methods of Preparation, Methods of Analysis, Pharmacology and List of References. These main sections are further divided to many sub-titles to cover most aspect of the drug in the light of the available literature. Among these sub-titles are the formulae, Elemental Analysis, physical characteristics which include constant of ionization, solubility, X-ray powder diffraction pattern, TGA, thermal conduct and spectroscopic and stability. Additionally, analytical techniques including Electrochemical, Spectrophotometric and chromatographic methods, ADME profiles and pharmacological effects were also discussed. Furthermore, methods and schemes are outlined for the preparation of the drug substance.

Ultrasound-guided continuous erector spinae plane block vs continuous thoracic epidural analgesia for the management of acute and chronic postthoracotomy pain: a randomized, controlled,double-blind trial.

Introduction: Postthoracotomy pain (PTP) is a severe pain complicating thoracic surgeries and its good management decreases the risk of PTP syndrome (PTPS). Objectives: This randomized controlled study evaluated the efficacy of ultrasound-guided continuous erector spinae plane block (ESPB) with or without dexmedetomidine compared with thoracic epidural analgesia (TEA) in managing acute postoperative pain and the possible emergence of PTPS. Methods: Ninety patients with chest malignancies planned for thoracotomy were randomly allocated into 3 equal groups. Group 1: TEA (20 mL of levobupivacaine 0.25% bolus, then 0.1 mL/kg/h of levobupivacaine 0.1%), group 2: ESPB (20 mL of levobupivacaine only 0.1% bolus every 6 hours), and group 3: ESPB (20 mL of levobupivacaine 0.25% and 0.5 µg/kg of dexmedetomidine Hcl bolus every 6 hours). Results: Resting and dynamic visual analog scales were higher in group 2 compared with groups 1 and 3 at 6, 24, and 36 hours and at 8 and 12 weeks. Postthoracotomy pain syndrome incidence was higher in group 2 compared with groups 1 and 3 at 8 and 12 weeks, whereas it was indifferent between groups 1 and 3. The grading system for neuropathic pain score was higher in group 2 compared with groups 1 and 3 at 8 and 12 weeks, whereas it was indifferent between groups 1 and 3. Itching, pruritis, and urine retention were higher in group 1 than in ESPB groups. Conclusion: Ultrasound-guided ESPB with dexmedetomidine is as potent as TEA in relieving acute PTP and reducing the possible emergence of chronic PTPS. However, the 2 techniques were superior to ESPB without dexmedetomidine. Erector spinae plane block has fewer side effects compared with TEA.

Regenerative Strategies in Treatment of Peripheral Nerve Injuries in Different Animal Models.

BACKGROUND: Peripheral nerve damage mainly resulted from traumatic or infectious causes; the main signs of a damaged nerve are the loss of sensory and/or motor functions. The injured nerve has limited regenerative capacity and is recovered by the body itself, the recovery process depends on the severity of damage to the nerve, nowadays the use of stem cells is one of the new and advanced methods for treatment of these problems. METHOD: Following our review, data are collected from different databases "Google scholar, Springer, Elsevier, Egyptian Knowledge Bank, and PubMed" using different keywords such as Peripheral nerve damage, Radial Nerve, Sciatic Nerve, Animals, Nerve regeneration, and Stem cell to investigate the different methods taken in consideration for regeneration of PNI. RESULT: This review contains tables illustrating all forms and types of regenerative medicine used in treatment of peripheral nerve injuries (PNI) including different types of stem cells " adipose-derived stem cells, bone marrow stem cells, Human umbilical cord stem cells, embryonic stem cells" and their effect on re-constitution and functional recovery of the damaged nerve which evaluated by physical, histological, Immuno-histochemical, biochemical evaluation, and the review illuminated the best regenerative strategies help in rapid peripheral nerve regeneration in different animal models included horse, dog, cat, sheep, monkey, pig, mice and rat. CONCLUSION: Old surgical attempts such as neurorrhaphy, autogenic nerve transplantation, and Schwann cell implantation have a limited power of recovery in cases of large nerve defects. Stem cell therapy including mesenchymal stromal cells has a high potential differentiation capacity to renew and form a new nerve and also restore its function.

Circulating miR-146b and miR-27b are efficient biomarkers for early diagnosis of Equidae osteoarthritis.

One of the most orthopedic problems seen in the equine is osteoarthritis (OA). The present study tracks some biochemical, epigenetic, and transcriptomic factors along different stages of monoiodoacetate (MIA) induced OA in donkeys in serum and synovial fluid. The aim of the study was the detection of sensitive noninvasive early biomarkers. OA was induced by a single intra-articular injection of 25 mg of MIA into the left radiocarpal joint of nine donkeys. Serum and synovial samples were taken at zero-day and different intervals for assessment of total GAGs and CS levels as well as miR-146b, miR-27b, TRAF-6, and COL10A1 gene expression. The results showed that the total GAGs and CS levels increased in different stages of OA. The level of expression of both miR-146b and miR-27b were upregulated as OA progressed and then downregulated at late stages. TRAF-6 gene was upregulated at the late stage while synovial fluid COL10A1 was over-expressed at the early stage of OA and then decreased at the late stages (P < 0.05). In conclusion, both miR-146b and miR-27b together with COL10A1 could be used as promising noninvasive biomarkers for the very early diagnosis of OA.

Evaluation of the accuracy of oscillometric non-invasive blood pressure measurement at the ankle in children during general anesthesia.

This study aimed to evaluate the accuracy of oscillometric blood pressure measurement at the ankle in children using invasive blood pressure as reference standard. This prospective observational study included children undergoing noncardiac surgery. Paired radial invasive and ankle non-invasive blood pressure measurements were obtained. Delta blood pressure was calculated as the difference between two consecutive readings. The primary outcome was the mean bias and agreement between the two methods using the Bland-Altman analysis. The ISO standard was fulfilled if the mean bias between the two methods was ≤ 5 ± 8 mmHg. Other outcomes included the trending ability of ankle blood pressure using the four-quadrant plot and the accuracy of ankle measurement to detect hypotension using area under receiver operating characteristic curve (AUC) analysis. We analyzed 683 paired readings from 86 children. The mean bias between the two methods for systolic, diastolic, and mean blood pressure (SBP, DBP, MAP) was - 7.2 ± 10.7, 4.5 ± 12.8, and - 1.8 ± 8.2 mmHg, respectively. The concordance rate of ankle blood pressure was 72%, 71%, and 77% for delta SBP, DBP and MAP, respectively. The AUC (95% confidence interval) for ankle MAP ability to detect hypotension was 0.91 (0.89-0.93) with negative predictive value of 100% at cut-off value ≤ 70 mmHg, We concluded that in pediatric population undergoing noncardiac surgery, ankle blood pressure was not interchangeable with the corresponding invasive readings with the ankle MAP having the least bias compared to SBP and DBP. An ankle MAP > 70 mmHg can exclude hypotension with negative predictive value of 100%.

Lapatinib: A comprehensive profile.

Lapatinib is an anticancer used for treatment of the patients with advanced metastatic breast cancer in conjunction with the chemotherapy drug capecitabine or with letrozole for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer. This comprehensive profile of Lapatinib gives more detailed information about the description, formulae, Elemental Analysis, Uses and application. Furthermore, methods and schemes are outlined for the preparation of the drug substance. The physical properties of the medication include constant of ionization, solubility, X-ray powder diffraction pattern, differential scanning calorimetry, thermal conduct and spectroscopic studies are investigated. The methods employed in bulk medicines and/or in pharmaceutical formulations to analyze the drug substance include spectrophotometric, electrochemical and the chromatographic methods are indicated. Other studies on this drug substance include drug stability, pharmaceutical applications, mechanism of action, pharmacodynamics, and a dosing information are also reviewed.

Crizotinib: A comprehensive profile.

Crizotinib, approved in 2011, was the first approved inhibitor targeting anaplastic lymphoma kinase (ALK) It used for treatment of the patients with metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive. This chapter provides a complete review of crizotinib including nomenclature, physiochemical properties, methods of preparation, identification techniques and various qualitative and quantitative analytical techniques as well as pharmacology of crizotinib. In addition, the chapter also includes review of several methods for separation of crizotinib using chromatographic techniques.

Ultrasound Guided Continuous Erector Spinae Plane Block versus Patient Controlled Analgesia in Open Nephrectomy for Renal Malignancies: A Randomized Controlled Study.

Background: It is critical to manage acute postoperative pain for patient satisfaction and better outcome. Erector spinae plane block (ESPB) can produce sensory blocking on both visceral and somatic levels. This study aimed to evaluate the ESPB efficacy in controlling acute postoperative pain in open nephrectomy for renal malignancies. Methods: This prospective randomized, controlled, open-label trial included 60 cases scheduled for open nephrectomy for renal malignancy under general anesthesia. Cases were assigned randomly into two equal groups. Group E administered continuous preoperative unilateral ESPB (20mL bupivacaine 0.25% bolus then 6 mL/h 0.1% for 48 hours). Group C administered intravenous (IV) patient-controlled analgesia (PCA) morphine (0.01 mg/kg/h). Postoperative analgesia was managed by morphine (3 mg IV in group E or 0.01 mg/kg bolus with a 15-min lockout in group C) to keep the visual analog scale (VAS) scores <4. Results: Intraoperative fentanyl consumption and total morphine consumption in 1st 48 hours postoperatively were significantly lower in group E than group C (P= 0.001 and <0.001, respectively). The time to first analgesic request was significantly longer in group E than group C (P <0.001). VAS scores at movement and rest were significantly lower in group E than group C (P <0.001). Conclusion: In renal malignancies, ESPB provided better analgesia with prolonged time and lower pain scores at both rest and movement compared to IV PCA following open nephrectomy.

Clinical, ultrasonographic and histopathological diagnosis of ceruminous gland tumors in cats.

Ceruminous gland tumor is the most common tumor of the ear canal in cats. Otoscopic examination of the ear tumor is so difficult due to narrowing of the external ear canal. The present study aimed to investigate clinical, ultrasonographic and histopathological characteristics of feline ceruminous gland neoplasm in cats. Ten cats with unilateral ear canal swelling were subjected to thorough physical and clinical investigations. Ultrasound of the ear canal and parotid gland was performed using 8.00 MHz linear probe. Tissue specimens were collected after surgical excision (total ear canal ablation) for histopathological examination. Clinical examination of the ceruminous tumors revealed firm pinkish mass obliterated the ear canal with purulent or bloody aural discharge. Ultrasound examination of the ear tumor was helpful in detecting the size, shape, echogenicity and extension of the tumors to the surrounding structures as well as the nature of the feline ceruminous tumor. Histopathological examination was the main diagnostic tool for detecting the nature of the ceruminous neoplasms.

Postmastectomy pain syndrome after preoperative stellate ganglion block: a randomized controlled trial.

BACKGROUND: This study investigated the effect of preoperative ultrasound (US) guided stellate ganglion block (SGB) with bupivacaine on the frequency of post mastectomy pain syndrome (PMPS). METHODS: Eighty patients scheduled for mastectomy with axillary dissection for breast cancer were included in this randomized controlled trial. Patients were randomized into two equal groups: Group A received US guided SGB one hour before surgery using five mL of 0.5% bupivacaine and multimodal systemic analgesia, Group B (control) received multimodal systemic analgesia only. Patients were followed up for six months. PMPS was assessed using the grading system for neuropathic pain (GSNP). Postoperative opioid consumption in the first 24 hours and numeric rating scale (NRS) were documented. Patient daily activity and functional capacity were evaluated using the Eastern Cooperative Oncology Group (ECOG) score. RESULTS: PMPS proportion was significantly lower in group A than group B (30% vs. 62.5%, P=0.004; 52% decrease [95% CI: 18.4%-71.8%]). Postoperative opioid consumption and NRS were significantly lower in group A as compared to group B. ECOG score was significantly higher in Group A than Group B. CONCLUSIONS: Following mastectomy with axillary dissection, preoperative US guided SGB is associated with less PMPS proportion, postoperative pain and opioid consumption and better patient daily activity and functional capacity.

Modified Pectoral Nerve Block versus Serratus Block for Analgesia Following Modified Radical Mastectomy: A Randomized Controlled Trial.

BACKGROUND: Modified pectoral nerves (PECSII) and serratus blocks have been recently used for analgesia in breast surgery, but evidence comparing their analgesic benefits is limited. This prospective randomized, controlled study aims to examine the analgesic efficacy and safety profile of ultrasound-guided PECSII versus serratus blocks in patients undergoing modified radical mastectomy (MRM) for breast cancer. PATIENTS AND METHODS: One-hundred and eighty adult females scheduled for MRM were randomly allocated to three groups. PECS group patients received a PECSII block with 30mL of bupivacaine 0.25%, whereas SAPB group received a serratus anterior plane block (SAPB) using the same volume of bupivacaine 0.25% before induction of anesthesia. The control group received general anesthesia alone. Outcomes included 24 hours morphine consumption, intraoperative fentanyl requirements, visual analogue scale (VAS) scores for pain at rest and during movement, time to first rescue analgesia, postoperative nausea and vomiting (PONV), and sedation scores. RESULTS: Both PECSII and serratus blocks were associated with reduced postoperative morphine consumption compared to the control group (p<0.001). Both blocks were associated with reduced intraoperative fentanyl requirements, VAS scores, and PONV as compared with the control group. Also, they were associated with prolonged time to first rescue analgesia and better sedation scores in comparison with the control group. However, there were no differences between both blocks for all outcomes. CONCLUSION: PECSII and serratus blocks provide similarly adequate analgesia following modified radical mastectomy. CLINICAL TRIAL REGISTRATION: NCT02946294.

Morphometric measurements of the feet of working donkeys Equus asinus in Egypt.

Working equids rely on sound, balanced hooves, but data describing the typical morphology of the legs and feet of working donkeys are currently lacking. To address this gap in knowledge, the front and hind feet of twenty healthy working donkeys were measured and compared. Hoof width, weight-bearing lengths, heel width, dorsal hoof wall length and lateral and medial heel length of the hoof wall were determined, as well as toe angle, heel angle, hoof pastern axis, coronary band angle and a measure of 'ground surface size'. Viewed from the ground surface of the foot, front feet were more rounded and significantly larger than hind feet. Measures of medial-lateral balance and toe-heel angle ratio were within the recommended healthy guidelines for horses. Hoof pastern axis was broken forward for the studied animals, which supports previous research suggesting that a broken forward hoof pastern axis is normal for donkeys, although further study would be required to confirm whether this conformation is natural. Significant correlations were found between estimated body mass and hoof width in both the front and hind feet. These measurements provide valuable insight into the relationship between hoof and body characteristics, which may aid the development of guidelines for the trimming and management of working donkey hooves. Further study is, however, advised to confirm natural hoof conformation.

Ultrasonographic examination of the normal caprine neonatal brain.

Ultrasonography is a safe, rapid, and non-invasive diagnostic tool that has been previously used for imaging infants and canine neonatal brains. The purpose of the present study was to describe the ultrasonographic appearance of the brain in clinically normal caprine neonates. Ultrasonographic examination was done on 12 day-old goat kids, transverse and sagittal transcranial scans were obtained through the frontal bone. Three image planes were recorded through transverse scans including plane I (level of the caudate nucleus), plane II (level of the rostral diencephalon) and plane III (level of the caudal diencephalon). Parallel post mortem examinations were done for two kids that died a day following examination due to accidental trauma by the dam. Reliable and repeatable ultrasonographic images of the goat kid's brain were described based on the gross post mortem findings. The head of the caudate nucleus was taken as an anatomical landmark in the plane I where it appeared as a curved hyperechoic structure. In plane II, the longitudinal fissure with its characteristic umbrella-like structure was taken as a landmark, while in plane III, the laterally located hyperechoic hippocampus was taken as a landmark. Normal ultrasonographic examination of the caprine neonatal brain represented the basis for diagnosing congenital brain lesions as well as intracranial hemorrhage.

The protective effect of losartan against sorafenib induced cardiotoxicity: Ex-vivo isolated heart and metabolites profiling studies in rat.

Sorafenib, a tyrosine kinase inhibitor that is used in the treatment of hepatocellular and renal cell carcinoma, was reported to induce cardiotoxicity. This study aimed to investigate the potential cardioprotective effect of losartan against sorafenib-induced cardiotoxicity in rat. Sorafenib significantly reduced the left ventricular pressure, heart rate dp/dt max & dp/dt min (indexes of myocardial contractility and relaxation; respectively), and prolonged both the systolic and diastolic periods. Coadminstration of losartan significantly reversed the effects of sorafenib on heart rate, dp/dt max and dp/dt min. In addition, there was a tendency for losartan to reverse sorafenib reduction in left ventricular pressure and perfusion pressure but it did not reach statistical significance. A GC-MS non-targeted based metabolites profiling of rat plasma revealed elevated metaboites, including urea and fatty acids levels, associated with sorafenib induced cardiotoxicity. However, only glycine and lactic acid were statistically significant. Interestingly, losartan co-administration with sorafenib restored these changes, and resulted in a significantly reduced glycine, urea and some fatty acids levels namely; Cis-vaccenic acid, oleic acid, stearic acid and undecanoic acid. In addition, based on histology results, losartan coadminitration almost obviated sorafenib-induced changes in cardiac tissues. The study suggests that losartan has the potential to exert a protective effect against sorafenib-induced cardiotoxicity.

Cigarette waste: Assessment of hazard to the environment and health in Riyadh city.

Cigarette waste/litter is considered a major environmental contamination problem worldwide as trillions of cigarettes are smoked worldwide and a large part of that, cigarette waste, is disposed of in the open areas including roads, parks, and streets, etc. cigarette litter is the most commonly found litter. It is mainly cigarette filter, made of cellulose acetate, and unburnt part of the tobacco filler. Filters from smoked cigarettes contain a significant amount of tar trapped in it. The tar contains thousands of chemicals and heavy metals. Both of these organic and inorganic constituents have been reported to be toxic to humans and cause a variety of diseases including inflammatory lung diseases, cardiovascular diseases, and cancers. Cigarette litter is a significant environmental concern as the chemicals and heavy metals can leach into the soil or water sources and pose threat to animals and plants, from there they can enter into the food chain as well. Several reports indicate toxicities to aquatic and terrestrial animals as they consumed cigarette litter. In the present investigation, cigarette litter was collected from 28 randomly selected locations in the Riyadh city to assess the risk to the environment. Cigarette litter, in the form of cigarette butts, was collected, counted, weighed and analyzed for heavy metal content. Data indicate the presence of a significant amount of cigarette litter on roadsides, streets, and parks in the Riyadh city. However, the investigation had its limitations as it did not focus on the absolute amount of cigarette litter vs the time. It also did not consider the amount of cigarette litter percent in the total waste discarded. The investigation presents the results of the screening of the cigarette litter present on the Riyadh city roads, streets, and parks. The findings raise concerns regarding the hazards the cigarette litter poses to the environment and human health. The investigation sheds the light on this unexplored aspect of smoking-associated issues in the Kingdom of Saudi Arabia.

COL2A1 and Caspase-3 as Promising Biomarkers for Osteoarthritis Prognosis in an Equus asinus Model.

Osteoarthritis (OA) is one of the most degenerative joint diseases in both human and veterinary medicine. The objective of the present study was the early diagnosis of OA in donkeys using a reliable grading of the disease based on clinical, chemical, and molecular alterations. OA was induced by intra-articular injection of 25 mg monoiodoacetate (MIA) as a single dose into the left radiocarpal joint of nine donkeys. Animals were clinically evaluated through the assessment of lameness score, radiographic, and ultrasonographic findings for seven months. Synovial fluid and cartilage samples were collected from both normal and diseased joints for the assessment of matrix metalloproteinases (MMPs) activity, COL2A1 protein expression level, and histopathological and immunohistochemical analysis of Caspase-3. Animals showed the highest lameness score post-induction after one week then decreased gradually with the progression of radiographical and ultrasonographic changes. MMP activity and COL2A1 and Caspase-3 expression increased, accompanied by articular cartilage degeneration and loss of proteoglycan. OA was successfully graded in Egyptian donkeys, with the promising use of COL2A1and Caspase-3 for prognosis. However, MMPs failed to discriminate between early and late grades of OA.

Erlotinib.

Erlotinib (OSI-774), marketed by Genentech as Tarceva®, is anticancer drug approved by US-FDA for the treatment of Non-Small Cell Lung Cancer (NSCLC) and Pancreatic Cancer. Erlotinib inhibited epidermal growth factor receptor (EGFR) that blocks tumor cell division, produces cell cycle arrest, and initiates programmed cell death in EGFR-overexpressing human tumor cells. This study presents a comprehensive profile of erlotinib, including detailed nomenclature, formula, elemental analysis, methods of preparation, physico-chemical characteristics, and methods of analysis (including spectroscopic, electrochemical, and chromatographic methods of analysis). Spectroscopic and spectrometric analyses include UV/vis spectroscopy, vibrational spectroscopy, nuclear magnetic resonance spectrometry ((1)H and (13)C NMR), and mass spectrometry. Chromatographic methods of analyses include thin layer chromatography, and high-performance liquid chromatography. Pharmacology of erlotinib including pharmacodynamics, mechanism of action, pharmacokinetics and drug-drug interactions were also presented. An appropriate table and figures were attached to each of the above mentioned sections along with total of 48 references.

Sorafenib.

Sorafenib (BAY-43-9006), marketed by Bayer as Nexavar® (USA), is anticancer drug approved by US-FDA for the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinoma. Sorafenib inhibited tumor growth and angiogenesis through targeting both the RAF/MEK/ERK pathway and receptor tyrosine kinases. This study presents a comprehensive profile of sorafenib, including detailed nomenclature, formula, elemental analysis, methods of preparation, physico-chemical characteristics, and methods of analysis (including spectroscopic, electrochemical, and chromatographic methods of analysis). Spectroscopic and spectrometric analyses include UV/vis spectroscopy, vibrational spectroscopy, nuclear magnetic resonance spectrometry ((1)H and (13)C NMR), and mass spectrometry. Chromatographic methods of analyses include thin layer chromatography and high-performance liquid chromatography. Only few stability indicating methods were found for quantification of sorafenib after exposing tablet dosage form to various stress conditions such as hydrolysis, oxidation, thermal stress, photo and UV light. However, none of these described methods were made to separate and quantify the degradation products. Pharmacology studies including pharmacodynamics, mechanism of action, pharmacokinetics and drug-drug interactions were also presented. An appropriate table and figures were attached to each of the above mentioned sections along with total of 55 references.