Ponatinib: A comprehensive drug profile.

Ponatinib is a prescription medication used to treat a rare form of blood cancer called Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (CML) that is resistant to other treatments. It belongs to a class of drugs called tyrosine kinase inhibitors, which work by blocking abnormal proteins that promote the growth of cancer cells. In this chapter, the synthesis methods and physicochemical properties of ponatinib were reviewed, besides the characterization of the ponatinib structure using different techniques such as elemental analysis, IR, UV, (1H and 13C) NMR, MS, and XRD. Furthermore, the compendial method for analysis of ponatinib was not found, while the literature review of a non-compendial method for analysis of ponatinib, such as spectroscopic, chromatographic, and immunoassay methods, was covered. Moreover, pharmacology and biochemistry were surveyed in the pharmacokinetic and pharmacodynamic studies.

Avanafil: A comprehensive drug profile.

Avanafil is an oral medication used to treat erectile dysfunction (ED). As a phosphodiesterase type 5 (PDE5) inhibitor, it functions by inhibiting the PDE5 enzyme, which ultimately results in increased levels of cyclic guanosine monophosphate (cGMP) and improved blood flow to the penis. Approved by the FDA in 2012, avanafil is recognised for its rapid onset of action, short half-life, and favourable side-effects profile. While it has been explored for other potential therapeutic applications, its current approved use is limited to ED and should be used as prescribed by a medical professional. This chapter provides a comprehensive review of avanafil, encompassing its nomenclature, physicochemical properties, methods of preparation, and identification. Various techniques for analysing avanafil, such as electrochemical analysis, spectrophotometric, spectrofluorimetric, and chromatographic techniques, are discussed. The pharmacology of avanafil, including its pharmacokinetics and pharmacodynamics, is also examined.

Comparative Study Between Dexmedetomidine with Bupivacaine and Bupivacaine Alone in Erector Spinae Plane Block for Postoperative Pain Control of Posterior Lumbosacral Spine Fixation Surgeries: A Randomized Controlled Trial.

Background: As posterior lumbosacral spine fixation surgeries are common spine procedures done nowadays due to different causes and mostly accompanied with moderate-to-severe postoperative pain, so should find effective postoperative analgesia for these patients. This study aimed to observe analgesic effect of dexmedetomidine combined with bupivacaine versus bupivacaine alone for erector spinae plane block ESPB for postoperative pain control of posterior lumbosacral spine fixation surgeries. Methods: Double-blind randomized controlled study including 90 patients who were randomly allocated into 3 groups (30 patients for each): Dexmedetomidine combined with bupivacaine (DB group), bupivacaine (B group), and saline (control) (S group). US-guided ESPB was performed preoperatively bilaterally in all patients of the 3 groups. All patients received intravenous patient-controlled postoperative analgesia with morphine and 1 gm intravenous paracetamol every 8 hours. Primary clinical outcomes were active (while mobilization) and passive (at rest) visual analog scale (VAS) pain score at first 24 hours measured every 2 hours, opioid consumption (number of PCA presses), and need for rescue analgesia. Other clinical outcomes included active and passive VAS pain score at second 24 hours, measured every 4 hours, opioid consumption, need for rescue analgesia, postoperative opioid side effects, and intraoperative dexmedetomidine side effects as bradycardia and hypotension. Results: Active and passive VAS pain scores, postoperative opioid consumption, need for rescue analgesia, and postoperative opioid side effects were significantly lower in DB group when compared to other groups (B and S groups). There were no additional intraoperative dexmedetomidine side effects as bradycardia and hypotension. The estimated effect-size r was -0.58 and Cohen's d was -1.46. Conclusion: Addition of dexmedetomidine to bupivacaine 0.25% in ESPB for postoperative pain control in patients of posterior lumbosacral spine fixation surgeries resulted in lower active and passive VAS pain scores, decreased postoperative opioid consumption, need for rescue analgesia and postoperative opioid side effects without additional intraoperative dexmedetomidine side effects. Clinicaltrialsgov Identifier: NCT05590234.

Antiviral activity of some benzo[g]quinazolines against coxsackievirus B4: biological screening and docking study.

BACKGROUND: Serotype coxsackievirus B (CVB) infection has been linked to viral myocarditis, dilated cardiomyopathy, meningitis, and pancreatitis in children and young adults. As of yet, no antiviral drug has been authorized for the treatment of coxsackievirus infection. Therefore, there is perpetual demand for new therapeutic agents and the improvement of existing ones. Benzo[g]quinazolines, the subject of several well-known heterocyclic systems, have risen to prominence and played a significant role in the development of antiviral agents, particularly those for anti-coxsackievirus B4 infection. METHODS: This study investigated the cytotoxicity of the target benzo[g]quinazolines (1-16) in the BGM cells line as well as their anti-coxsackievirus B4 activity. Determination of CVB4 titers using a plaque assay. RESULTS: Most of the target benzoquinazolines exhibited antiviral activity, however, compounds 1-3 appeared to be the most effective (reduction percentages of 66.7, 70, and 83.3%, respectively). The binding mechanisms and interactions of the three most active 1-3 with the constitutive amino acids in the active site of the multi-target of coxsackievirus B4 (3Clpro and RdRp) targets were also investigated using molecular docking. CONCLUSION: The anti coxsackievirus B4 activity has resulted, and the top three active benzoquinazolines (1-3) have bonded to and interacted with the constitutive amino acids in the active region of the multi-target coxsackievirus B4 (RdRp and 3Clpro). Further research is required in the lab. to determine the exact benzoquinazolines mechanism of action.

Characterizing Biomass Yield and Nutritional Value of Selected Indigenous Range Species from Arid Tunisia.

Rangelands of Tunisia show a great indigenous species diversity with considerable potential as forage for livestock. However, information on their fodder yield and quality is scanty and restricted to few species. The objective of the study was to evaluate the nutritive values of selected key perennial species based on their biomass yield, chemical composition, in vitro organic matter digestibility (IVOMD), and mineral composition. The species evaluated included four grass species (Stipa lagascae Roem. and Schult., Stipa tenacissima L., Stipagrostis plumosa (L.) Munro ex T. Anderson, and Stipagrostis pungens (Desf.) de Winter.) and eight shrub species (Anthyllis henoniana Coss. ex Batt., Argyrolobium uniflorum (Deene.) Jaub. and Spach., Echiochilon fruticosum Desf., Gymnocarpos decander Forssk., Helianthemum kahiricum Delile., Helianthemum lippii (L.) Dum. Cours., Plantago albicans L. and Rhanterium suaveolens Desf.). Results showed that shrub species contained higher concentrations of the crude protein (CP), acid detergent lignin (ADL), but lower neutral detergent fiber (aNDFom) and acid detergent fiber (ADFom) concentrations than grasses. The greatest concentration of CP was 135 g/kg DM for R. suaveolens. The greatest aNDFom concentration was found within the grasses with maximum of 744.5 g/kg DM in S. plumosa. The shrub species E. fruticosum, A. uniflorum, P. albicans, G. decander, R. suaveolens, and A. henoniana had the highest IVOMD with over 500 g/kg DM and have the potential to supply energy to livestock. Overall, the moderate to high protein, low fiber, and high in vitro digestibility measured for shrubs, suggest they have high nutritional values and can be used to enhance local livestock production.

Serotyping and Antibiotic Susceptibility of Invasive Streptococcus agalactiae in Egyptian Patients with or without Diabetes Mellitus.

Streptococcus agalactiae serotype distribution and its antibiotic susceptibility affect disease prevention strategies, but the serotype distribution varies among patient groups. The objectives of this study were to establish the group B Streptococcus (GBS) serotype distribution in patients from Egypt and to assess antibiotic sensitivity of invasive GBS isolates. A total of 490 patients participated in this multicenter study; 160 had urinary tract infection, 115 complained of diabetic foot ulcers, 125 men had genital tract infections, and 30 women females had genital tract infections. Others had bronchopneumonia, otitis media, synovitis, or meningitis. Serotyping of the isolated GBS was performed at the CDC in the United States. Antibiotic sensitivity patterns were determined using the disk diffusion method. In men, the most common serotypes were II, III, and V, whereas types Ia, II, III, and V were isolated from women. Macrolides (erythromycin) resistance occurred in 4.1% of the isolates; 10.2% were resistant to both clindamycin and inducible resistance of macrolides, lincomycin, and streptogramin; 17.3% were resistant to quinolones; and 95.9% were resistant to tetracyclines. GBS primarily infected the urinary tract, skin, soft tissue, and genital tract in both genders. Isolates were sensitive to beta-lactam drugs, vancomycin, and linezolid; 14.0% were resistant to macrolides with or without clindamycin. Only 6.0% of the strains were sensitive to tetracyclines. Although GBS causes invasive infections in Egyptian adults, it rarely causes neonatal meningitis or sepsis. Future studies should determine whether GBS isolates are transmitted sexually, by performing a follow-up study of the partner of the infected patient.

Lysosomal Storage Disorders in Egyptian Children.

OBJECTIVE: To describe the spectrum, relative prevalence and molecular background of lysosomal storage disorders in Egypt. METHODS: The authors evaluated the selective screening program for the diagnosis of lysosomal storage disorders in Egyptian children presenting to the inherited metabolic disease unit at Cairo University Children's Hospital, the largest tertiary care pediatric hospital in Egypt, over a six-year period (April 2008 through April 2014). During this period, 1,065 suspected children were assessed clinically, biochemically and some genetically. RESULTS: Two hundred and eleven children (aged 44 ± 32 mo; 56 % boys, 82 % with consanguineous parents) were confirmed with 21 different lysosomal disorders. The diagnostic gap ranged between 2 mo and 14 y (average 25 mo). Mucopolysaccharidoses were the most common group of diseases diagnosed (44.5 %), while Maroteaux-Lamy, Gaucher and nephropathic cystinosis were the most commonly detected syndromes (17.1, 14.7 and 13.7 %, respectively). Eighty mutant alleles and 17 pathogenic mutations were detected in 48 genetically assessed confirmed patients (30 Gaucher, 16 cystinosis and two Niemann-Pick type C patients). CONCLUSIONS: This report is the first to describe relative frequency and spectrum of clinical and molecular data in a large cohort of Egyptian lysosomal patients. The crude estimate denotes that over 80 % of Egyptian lysosomal patients do not have access to optimal diagnosis. Upgrading diagnostic and genetic services for lysosomal storage disorders in Egypt is absolutely necessary.

Inborn errors of metabolism detectable by tandem mass spectrometry in Egypt: The first newborn screening pilot study.

OBJECTIVES: To estimate the burden of metabolic disorders detectable by tandem mass spectrometry in Egypt, through a pilot expanded newborn screening programme at Cairo University Children's Hospital in 2008, and examining the results of 3,900 clinically at-risk children, investigated at Cairo University Children's Hospital for the same disorders over the past 7 years using the same technology. METHODS: Dried blood spots of 25,276 healthy newborns from three governorates in Upper, Middle, and Lower Egypt were screened, to give a representative sample of the Egyptian newborn population. Based on the pilot study outcomes and the results of clinically suspected children, we estimated the total birth prevalence of tandem mass spectrometry detectable metabolic disorders, and the relative frequency of several individual disorders. RESULTS: Among the healthy newborns, 13 metabolic disorder cases (five phenylketonuria [1:5,000], two methylmalonic acidemia, and isovaleric acidemia [1:12,500], one each of maple syrup urine disease, propionic acidemia, ß-ketothiolase deficiency, and primary carnitine deficiency [1:25,000]) were confirmed, giving a total birth prevalence of 1:1944 live births. Among the clinically suspected children, 235 cases were diagnosed, representing a much wider disease spectrum. CONCLUSIONS: Egypt has one of the highest reported birth prevalence rates for metabolic disorders detectable by tandem mass spectrometry. Early diagnosis and management are crucial for the survival and well-being of affected children. A nationwide NBS programme by tandem mass spectrometry is recommended.

Selective screening for inborn errors of metabolism by tandem mass spectrometry in Egyptian children: a 5 year report.

OBJECTIVE: In order to enhance awareness and promote registry for inborn errors of metabolism (IEMs) in Egypt, we aimed to evaluate the prevalence and main clinical findings of IEMs detectable by tandem mass spectrometry (MS/MS) among high risk pediatric patients presenting to our tertiary care facility at Cairo University Children's Hospital over a period of 5 years and to compare the disease burden in Egypt in the absence of a national screening program for inherited metabolic disorders with other populations. METHODS: During this period 3380 Egyptian children were suspected of having IEMs based on clinical/laboratory presentation and were analyzed by MS/MS. Confirmatory testing was performed according to flagged analyte by MS/MS using a different sample type such as plasma or urine or by a different technique such as GC/MS. RESULTS: A relatively high number of patients (203/3380 (6%)) were confirmed with 17 different types of IEMs. Averages for age at diagnosis for different disorders ranged from 2.5 months to 6.6 years with general developmental delay and irreversible neurological damage being the most common presenting features (75.9% and 65.5%, respectively). Amino acid disorders (127/203 (62.6%)), mainly phenylketonuria (100/203 (49.3%)), were the most encountered, followed by organic acidemias (69/203 (34%)), while fatty acid oxidation defects (7/203 (3.4%)) were relatively rare. 88% of patients were born to consanguineous parents. CONCLUSIONS: The development of a nationwide screening program for IEMs is mandatory for early detection of these potentially treatable disorders, prompt and properly timed therapeutic intervention and prevention of the devastating neurological outcomes.

Clinical, neuroimaging, and genetic characteristics of megalencephalic leukoencephalopathy with subcortical cysts in Egyptian patients.

BACKGROUND: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare and genetically heterogeneous cerebral white matter disease. Clinically, it is characterized by macrocephaly, developmental delay, and seizures. We explore the clinical spectrum, neuroimaging characteristics, and gene involvement in the first patients with megalencephalic leukoencephalopathy with subcortical cysts described from Egypt. PATIENTS: Six patients were enrolled from three unrelated families. Patient inclusion criteria were macrocephaly, developmental delay, normal urinary organic acids, and brain imaging of diffuse cerebral white matter involvement. Direct sequencing of the MLC1 gene in patients' families and GliaCAM in one questionable case was performed using BigDye Terminator cycle sequencing. RESULTS: Clinical heterogeneity, both intra- and interfamilial, was clearly evident. Developmental delays ranged from globally severe or moderate to mild delay in achieving walking or speech. Head circumference above the ninety-seventh percentile was a constant feature. Neuroimaging featured variability in white matter involvement and subcortical cysts. However, findings of posterior fossa changes and brain stem atrophy were frequently (66.6%) identified in these Egyptian patients. Discrepancy between severe brain involvement and normal mental functions was evident, particularly in patients from the third family. MLC1 mutations were confirmed in all patients. Deletion/insertion mutation in exon 11 (c.908-918delinsGCA, p.Val303 Gly fsX96) was recurrent in two families, whereas a missense mutation in exon 10 (c.880 C > T, p.Pro294Ser) was identified in the third family. CONCLUSIONS: This report extends our knowledge of the clinical and neuroimaging features of megalencephalic leukoencephalopathy with subcortical cysts. It confirms the apparent lack of selective disadvantage of MLC1 mutations on gamete conception and transmission as supported by the presence of multiple affected siblings in Egyptian families.