Vaccine-associated complications: a comparative multicenter evaluation among dental practitioners and dental students—which candidate vaccine is more safe in SARS COV II, Gam-COVID-Vac (Sputnik V), ChAdOx1 nCoV-19 (AstraZeneca), BBV152 (Covaxin), or BBIBP-CorV(Sinopharm)?

Background The rapidly developed vaccines against the severe acute respiratory syndrome coronavirus 2 carry a risk of provoking side effects. This study aimed to evaluate current vaccination non-serious/serious side effects. Methods A multicenter electronic questionnaire via an online platform was conducted over a 1-week period among vaccinated dental staff and dental students inquiring whether they experienced vaccine-related side-effects after vaccine administration. Results A total of 1205 respondents with a mean age of 39 (SD: 12) were retained for the analyses. The following vaccines were reported; Gam-COVID-Vac (Sputnik V), ChAdOx1 nCoV-19 (AstraZeneca), BBV152 (Covaxin), or BBIBP-CorV (Sinopharm). The majority of respondents received ChAdOx1 nCoV-19 (51.1%) and Gam-COVID-Vac (37.6%). The symptoms most frequently reported after vaccination were fatigue (79%), local pain in the injection site (77.4%), malaise (73%), and body pain (71.1%). Enrollees reported more onset of reactions on 0–12 h (44.1%) and 12–24 h (29.0%) after vaccine administration (p value <0.001). In 75.7%, the side effects last for up to 3 days. Merely 5.5% of cases reported the presence of side effects after the first week. Individuals with a history of SARSCoV-2 and other infections (MERS, influenza, and EBV) were more likely to report a number of unserious systemic side effects. Conclusion The commonly reported adverse events were in line with similar studies. We have concerns with the frequency of serious adverse effects. This work necessitates the need for further clinical assessments with larger sample sizes.

Acetazolamide modulates intracranial pressure directly by its action on the cerebrospinal fluid secretion apparatus

Elevated intracranial pressure (ICP) is observed in many neurological pathologies, e.g. hydrocephalus and stroke. This condition is routinely relieved with neurosurgical approaches, since effective and targeted pharmacological tools are still lacking. The carbonic anhydrase inhibitor, acetazolamide (AZE), may be employed to treat elevated ICP. However, its effectiveness is questioned, its location of action unresolved, and its tolerability low. Here, we employed in vivo and ex vivo approaches to reveal the efficacy and mode of action of AZE in the rat brain. The drug effectively reduced the ICP, irrespective of the mode of drug administration and level of anaesthesia. The effect occurred via a direct action on the choroid plexus and an associated decrease in cerebrospinal fluid secretion, and not indirectly via the systemic action of AZE on renal and vascular processes. Upon a single administration, the reduced ICP endured for approximately 10 h post-AZE delivery with no long-term changes of brain water content or choroidal transporter expression. However, a persistent reduction of ICP was secured with repeated AZE administrations throughout the day. Future specific targeting of choroidal carbonic anhydrases may limit the systemic side effects, and therefore enhance the treatment tolerability and effectiveness in select patient groups experiencing elevated ICP.

Microemulsion Based Nanostructures for Drug Delivery

Most of the active pharmaceutical compounds are often prone to display low bioavailability and biological degradation represents an important drawback. Due to the above, the development of a drug delivery system (DDS) that enables the introduction of a pharmaceutical compound through the body to achieve a therapeutic effect in a controlled manner is an expanding application. Henceforth, new strategies have been developed to control several parameters considered essential for enhancing delivery of drugs. Nanostructure synthesis by microemulsions (ME) consist of enclosing a substance within a wall material at the nanoscale level, allowing to control the size and surface area of the resulting particle. This nanotechnology has shown the importance on targeted drug delivery to improve their stability by protecting a bioactive compound from an adverse environment, enhanced bioavailability as well as controlled release. Thus, a lower dose administration could be achieved by minimizing systemic side effects and decreasing toxicity. This review will focus on describing the different biocompatible nanostructures synthesized by ME as controlled DDS for therapeutic purposes.

Adhesion Molecule Targeted Therapy for Non-Infectious Uveitis

Non-infectious uveitis (NIU) is an inflammatory eye disease initiated via CD4+ T-cell activation and transmigration, resulting in focal retinal tissue damage and visual acuity disturbance. Cell adhesion molecules (CAMs) are activated during the inflammatory process to facilitate the leukocyte recruitment cascade. Our review focused on CAM-targeted therapies in experimental autoimmune uveitis (EAU) and NIU. We concluded that CAM-based therapies have demonstrated benefits for controlling EAU severity with decreases in immune cell migration, especially via ICAM-1/LFA-1 and VCAM-1/VLA-4 (integrin) pathways. P-selectin and E-selectin are more involved specifically in uveitis related to vasculitis. These therapies have potential clinical applications for the development of a more personalized and specific treatment. Localized therapies are the future direction to avoid serious systemic side effects.

Nanoemulgel: a Promising Nanolipoidal-Emulsion Based Drug Delivery System in Managing Psoriasis

Nanomedicine, a novel concept, bears much hope in delivering drug candidates having low solubility and bioavailability. Nano-emulgel, one of the emerging tools, is considered as ideal carriers for the topical delivery of lipophilic drugs to overcome these challenges in the management of psoriasis and related skin problems. Psoriasis is an auto-immune and chronic inflammatory disease affecting 2-3% population of the world. Current available treatment of psoriasis has limitations such as systemic side effects and low percutaneous permeation, which evokes a dire need to develop an alternative lipoidal nanocarrier system. Nano-emulgel is basically formed by admixing nanoemulsion system with a hydrogel matrix using both high and low energy methods. Various literatures have been reported for lipoidal nanocarriers in topical treatment suggesting reduced dose, improved percutaneous absorption and better bioavailability of lipophilic drugs with nano-emulgel delivery via topical route. Several approved marketed preparations are available that strongly support the stability of these nanocarriers in respect to its efficacy and safety. This supports the fact of using topical nano-emulgel system to deliver lipophilic drugs to overcome the sufferings from oral delivery and improved patient compliance. Therefore, it is suggested as a potential system that can be used for an effective management of psoriasis via topical route in near future. Dhaka Univ. J. Pharm. Sci. 20(2): 235-246, 2021 (December)

Botulinum toxin in cancer therapy—current perspectives and limitations

Different serotypes of botulinum toxins (BoNTs) act upon different types of SNARE proteins. This property is used in aesthetic medicine to treat certain eye disorders such as crossed eyes (strabismus) and uncontrolled blinking (blepharospasm), to treat muscle spasms or movement disorders, and, for the two last decades, more and more often, to provide support in cancer therapy, especially so as to obtain analgesic effects upon spastic conditions. The limited literature data also suggests that the addition of BoNTs to the culture of cancer cell lines reduces cell growth, and mitotic activity, and promotes their apoptosis. BoNTs have several advantages that can be emphasized: BoNTs act on both perfusion and oxygenation; moreover, BoNTs are considered to be safe and free of systemic side effects upon administration. Recently, advances in molecular biology techniques have allowed a wide variety of novel BoNT constructs with alternative functions. These constructs could be assessed as potential new classes of anti-cancer drugs. This creates new potential perspectives in the wider use of non-toxic modified BoNT constructs in cancer therapy. In the light of the mentioned premises and existing literature reports, the aim of this review is to summarize current data and reports considering BoNT use in cancer therapy. Key points •Botulinum toxin (BoNTs) may be useful in cancer treatment. •Botulinum toxin can serve as an analgesic after cancer radiotherapy. •Botulinum toxin has the ability to inhibit tumor growth and promote apoptosis of neoplastic cells.

Standardized Quantitative Evaluation of Clinical Effectiveness and Side Effect Profile of Subcutaneous and Sublingual Allergen-Specific Immunotherapy in Children: A 5-Year Single Center Experience

Objective: Allergen-specific immunotherapy (allergen-SIT) is a treatment method with variable efficacy in allergic diseases. This study aimed to investigate the effectiveness of allergen immunotherapy, frequency of LRs and SRs and variables affecting these parameters in patients who underwent allergen-SIT. Materials and Methods: In this study, the recorded data of 81 patients, who received subcutaneous (SCIT) or sublingual (SLIT) allergen immunotherapy for respiratory allergic diseases between 2014 and 2019, were analyzed. In asthma and/or allergic rhinoconjunctivitis (ARC) patients, the effectiveness of treatment was evaluated by analysing the change rates in disease symptom, medication and combined scores (symptom + medication) and visual analog score (VAS). Treatment success was defined by the degree of decrease in scores as; high response above 50%; low response between 20-50%; and failure <20%.Results: The mean age of allergen-SIT initiation was 11.4± 3.1 years. Diagnostic distributions of the patients were asthma (± ARC) in 64.2%, and ARC (without asthma) in 35.8%. The mode of allergen-SIT was SCIT in 77.8% (65% asthma and 35% ARC) and SLIT in 22.2% (61.1% asthma and 38.9% ARC). The main allergens used in allergen-SIT were mite (79%), grass-grain pollen (33.3%), alternaria (9.9%) and olea (8.6%). There was a significant decrease in symptoms, medication, combined and VAS scores in the asthma and ARC groups (p <0.0001), when end-SCIT values were compared to baseline. SLIT also resulted in significant decreases in these scores except asthma medication score. Among the asthma patients the rate of high-responders was 88.8% by SCIT and 50% by SLIT, according to combined asthma score. Among the ARC (without asthma) patients the rate of high-responders was 100% for both SCIT and SLIT. SCIT resulted in local (LR) and systemic side effects (SR) in 18% and 0.6% (all Grade I and Grade II) of the total injections performed. A high number of total injections was significantly associated with higher LR and SR rates. While LR was observed in 16.6% of the patients who underwent SLIT, no systemic reaction was found in any of the patients. Conclusion: SCIT was highly successful in the treatment of asthma and ARC in terms of the degree of therapeutic response. SLIT resulted in a high rate of good response in ARC patients, but a lower response degree in asthmatic patients. Systemic side effects were very low as a result of close risk monitoring and the dose adjustments performed. Keywords: Allergen-specific immunotherapy, SCIT, SLIT, efficacy, symptom score, medication score, visual analog score, side effects

Bevacizumab-induced isolated oculomotor nerve palsy in glioblastoma multiforme

Introduction: Bevacizumab, a monoclonal antibody against the vascular endothelial growth factor receptor, is the standard treatment of recurrent glioblastoma multiforme. In addition to common systemic side effects of bevacizumab, there are rare cases of cranial nerve palsy. Case report: We report a case of transient oculomotor nerve palsy after systemic administration of bevacizumab. Twenty-four hours after the systemic infusion of bevacizumab, transient oculomotor nerve palsy developed in a 49-year-old male patient. In the cranial MRI, there was no malignancy-related progression. Management and outcome: Bevacizumab treatment was discontinued. Methylprednisolone was started considering that bevacizumab increased the inflammatory response. Oculomotor nerve palsy resolved in 14 days. Discussion: There are many side effects of bevacizumab whose mechanisms of action have not been fully explained. Cranial nerve involvement is rarely reported. Our case is the first reported case of bevacizumab-induced oculomotor nerve palsy.

Antibody Response and Safety After mRNA-1273 SARS-CoV-2 Vaccination in Peritoneal Dialysis Patients – the Vienna Cohort

BackgroundDialysis patients are at high risk for a severe clinical course after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Safety and early immune responses after mRNA-based vaccination have been reported mostly in patients on hemodialysis (HD), whereas reports of peritoneal dialysis (PD) patients remain rare.MethodsIn this retrospective observational study, 39 PD patients had received two doses of the mRNA-1273 Moderna® vaccine. We analyzed SARS-CoV-2 Spike (S) antibody titers 4 weeks after each dose of mRNA-1273 and report local and systemic side effects in PD patients that occurred within one week after each mRNA-1273 dose. Using a quantile regression model we examined factors that might influence SARS-CoV-2 S antibody levels in PD patients.ResultsFour weeks after the first dose of mRNA-1273 vaccine 33 of 39 (84.6%) PD patients seroconverted and presented with 6.62 U/mL (median; IQR 1.57-22.5) anti-SARS-CoV-2 S antibody titers. After the second dose, 38 of 39 (97.4%) PD patients developed anti-SARS-CoV-2 S antibodies and titers increased significantly (median 968 U/mL; IQR 422.5-2500). Pain at the injection site was the most common local adverse event (AE) (71%). Systemic AEs occurring after the first dose were mostly fatigue (33%) and headache (20%). No severe systemic AEs were reported after the first injection. After the second dose the incidence and the severity of the systemic AEs increased. The most common systemic AEs were: fatigue (40.5%), headache (22.5%), joint pain (20%), myalgia (17.5%) and fever (13%). Lower Davies Comorbidity Score (p=0.04) and shorter dialysis vintage (p=0.017) were associated with higher antibody titers after the first dose. Patients with higher antibody titers after the first dose tended to have higher antibody titers after the second dose (p=1.53x10-05).ConclusionsPeritoneal dialysis patients in this cohort had a high seroconversion rate of 97.4%, showed high antibody titers after full vaccination and tolerated the anti-SARS-CoV-2 mRNA-1273 vaccine well without serious adverse events.