A comprehensive review on Brigatinib – A wonder drug for targeted cancer therapy in non-small cell lung cancer

The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90?mg of brigatinib for 7?days and then 180?mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.     

Prevalence of medical conditions among patients attending dental teaching clinics in northern Jordan

AIM: This study was conducted to estimate the prevalence of self reported medical conditions among dental patients attending dental teaching clinics in north Jordan. METHODS AND MATERIALS: A total of 1,509 patients were included, of which 46.1% were males and 53.9% were females. All age groups were included and ranged between 14 and 78 years. The findings were analyzed in relation to age and gender. RESULTS: Overall, gastrointestinal disease was most prevalent (11.9%), followed by bleeding tendencies (9.3%), renal disorders (8.7%), respiratory disease (8.3%), and hypertension (6.4%). Only 3.2% of the participants reported having antibiotics prescribed for them prior to a dental procedure for prophylactic purposes. CONCLUSION: Due to the high frequency of medical conditions, thorough evaluation of patients' medical and dental care histories should be a mandatory first step in their management.     

Severe hepatotoxicity with jaundice associated with paroxetine

Hepatotoxicity due to paroxetine, a selective serotonin reuptake inhibitor, is very rare, and to the best of our knowledge, only five cases of liver injury in association with paroxetine have previously been reported in the medical literature. We describe the clinical, biochemical, and pathological findings in a patient with paroxetine hepatotoxicity, which was reversed after withdrawal of the drug. The present case and the others previously reported suggest that hepatotoxicity should be taken into account as a rare complication, sometimes severe, that may occur with paroxetine.     

Breakdown of Phosphatidylserine Asymmetry Following Treatment of Erythrocytes with Lumefantrine

Background: Lumefantrine, a commonly used antimalarial drug, inhibits hemozoin formation in parasites. Several other antimalarial substances counteract parasitemia by triggering suicidal death or eryptosis of infected erythrocytes. Eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine-exposure at the erythrocyte surface. Signaling involved in eryptosis include increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i), formation of ceramide, oxidative stress and/or activation of p38 kinase, protein kinase C (PKC), or caspases. The present study explored, whether lumefantrine stimulates eryptosis. Methods: Cell volume has been estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, [Ca²⁺]_i from Fluo3-fluorescence, reactive oxygen species from 2'',7''-dichlorodihydrofluorescein-diacetate fluorescence, content of reduced glutathione (GSH) from mercury orange fluorescence, and ceramide abundance from binding of fluorescent antibodies in flow cytometry. Results: A 48 h exposure to lumefantrine (3 µg/mL) was followed by a significant increase of annexin-V-binding without significantly altering forward scatter, [Ca²⁺]_i, ROS formation, reduced GSH, or ceramide abundance. The annexin-V-binding following lumefantrine treatment was not significantly modified by p38 kinase inhibitors SB203580 (2 μM) and p38 Inh III (1 μM), PKC inhibitor staurosporine (1 µM) or pancaspase inhibitor zVAD (1 or 10 µM). Conclusions: Lumefantrine triggers cell membrane scrambling, an effect independent from entry of extracellular Ca²⁺, ceramide formation, ROS formation, glutathione content, p38 kinase, PKC or caspases.     

Successful treatment of relapsing autoimmune thrombotic thrombocytopenic purpura with rituximab

Thrombotic thrombocytopenic purpura (TTP) is a rare but life‐threatening condition characterized by thrombotic microangiopathy. The standard treatment for TTP is plasmapheresis. For refractory or relapsing cases, various immunosuppressive agents have been tried, and among them rituximab has shown promising results. TTP is rarer in the pediatric age group and the use of rituximab in children with TTP is limited. Reported herein is the successful treatment of relapsing autoimmune TTP with rituximab in a 12‐year‐old girl.     

Preparation and optimization of aloe ferox gel loaded with Finasteride-Oregano oil nanocubosomes for treatment of alopecia

Alopecia areata is a skin disorder characterized by scarless, localized hair loss that is usually managed by topical treatments that might further worsen the condition. Therefore, the current study aimed to develop nano-cubosomes loaded with finasteride (FI) and oregano oil (Or) to improve drug solubility and permeation through skin and then incorporate it into an aloe ferox gel base. An l-optimal coordinate exchange design was adopted to optimize nano-cubosomes. Phytantriol and Alkyl Acrylate were employed as the lipid material, and surfactant respectively for cubosomes manufacture. The produced formulations were assessed for their particle size, entrapment efficiency (EE%), FI steady-state flux (Jss) and minimum inhibitory concentration (MIC) against Pro-pionibacterium acnes. Optimal FI-Or-NCu had a particle size of 135 nm, EE% equals 70%, Jss of 1.85 μg/cm2.h, and MIC of 0.44 μg/ml. The optimum formulation loaded gel gained the highest drug release percent and ex vivo skin permeation compared to FI aqueous suspension, and pure FI loaded gel. Aloe ferox and oregano oil in the optimized gel formulation had a synergistic activity on the FI permeation across the skin and against the growth of p. acne bacteria which could favor their use in treating alopecia. Thus, this investigation affirms the ability of FI-Or-NCu loaded aloe ferox gel could be an effective strategy that would enhance FI release and permeation through skin and maximize its favorable effects in treating alopecia.     

Early infection in post-autologous hematopoietic stem cell transplant patients: Princess Noorah Oncology Center experience

Objectives:To assess local epidemiology and risk factors for bacterial, fungal, and viral infections among the autologous bone marrow transplant population.Methods:This study is a retrospective correlational cohort design comprising 150 adult patients who underwent autologous transplants at Princess Noorah Oncology Center, Jeddah, Saudi Arabia between 2014 and 2020.Results:The study findings indicate that bacterial infection prevalence differed significantly across the different disease status pre-salvage as patients with the relapsed disease were more likely to have bacterial infections. The median of engraftment days differed significantly between those who had a bacterial infection and those who did not. Interestingly, previous pneumonia infection had a positive relationship with the number of hospital stays.Conclusions:Bacterial infections are the dominant type of infection among the autologous patient population. The research reflects authentic practice and reports unique characteristics of autologous transplant patients in terms of the prevalence and types of infection these patients experience.     

Perceived awareness of sleep paralysis phenomenon (old hag syndrome) and its most common risk factors among people from Al-Ahsa,Saudi Arabia

Objectives:To assess prevalence and perception of sleep paralysis and its relationship with socioeconomic determinants, and risk factors in a cross-sectional sample of Saudi general population from Al-Ahsa city.Methods:A cross-sectional sampling survey was conducted during 2020 to 2021. The targets were aged above 18 and belonged to Al-Ahsa. Patients were sent self-reported anonymous questionnaires to complete.Results:A total of 524 participants, whose ages ranged from 18 to 60 years, were analyzed. Among 85.7% of participants aged 55 years and over, compared to 65.8% of those who were aged under 35, 379 (72.3%) respondents were females. Moreover, 438 (83.6%) participants were university graduates, 271 (51.7%) were students and 40.8% had psychological disorders including anxiety (25.2%) and depression (5.7%). Family history of sleep paralysis was reported by 369 (70.4%) participants. A total of 97.5% study participants were aware of sleep paralysis.Conclusion:Sleep paralysis is a common occurrence in people residing in Al-Ahsa, Saudi Arabia. A considerable number of the society held wrong beliefs regarding sleep paralysis. Therefore, raising public of identity of sleep paralysis is crucial. We recommend applying the study in other cities within Saudi Arabia to identify common risk factors and perceptions among the society.