A Comprehensive Review of the Mechanism, Efficacy, Safety, and Tolerability of Ubrogepant in the Treatment of Migraine.

Ubrogepant is an innovative medication designed for the acute treatment of migraine, a debilitating neurological condition that profoundly impairs quality of life, productivity, and social interactions. This comprehensive review assesses the efficacy, safety, tolerability, and mechanism of action of ubrogepant through a rigorous methodology, including an in-depth literature review from reputable databases like PubMed, Web of Science, Embase, Scopus, and Cochrane. Classified as a calcitonin gene-related peptide (CGRP) receptor antagonist, ubrogepant has emerged as a potential revolutionary medication for migraine treatment. CGRP is a peptide integral to migraine pathophysiology, and its blockade has demonstrated great therapeutic potential. Unlike triptans, known for their cardiovascular risks, ubrogepant lacks vasoconstrictive properties, making it a safer alternative for a broader patient population. Ubrogepant offers significant potential for pain relief, symptom reduction, and restoration of normal function during a migraine attack, and it outperforms placebo in terms of efficacy. It also presents favorable safety, with generally mild adverse drug events (ADEs), such as nausea, dizziness, and somnolence, similar to placebo effects. Consistent results from clinical trials confirm its tolerability, with minor ADEs and no safety alerts for the tested doses, indicating that ubrogepant is a safe and well-tolerated option for migraine treatment. As an effective oral medication, ubrogepant could be an alternative to traditional acute migraine treatments. Its benefits include a unique mechanism of action, rapid onset, and favorable safety profile. However, specific contraindications, such as hypersensitivity, severe hepatic impairment, concurrent use of CYP3A4 inhibitors, pregnancy or breastfeeding, and uncontrolled hypertension, require caution or avoidance of ubrogepant. Despite these limitations, ubrogepant signals a promising new direction in migraine therapeutics.

Anaplastic Meningioma Presenting as a Left Parietal Mass: A Case Report.

BACKGROUND Meningiomas are slow-growing tumors attached to the dura mater and are composed of neoplastic meningothelial cells. The tumors are most commonly located in convexities, and it is relatively rare to find such a growth in the parietal region such as the one presented in this case report. CASE REPORT Because of its uncommon presentation, we hereby report the case of a 67-year-old, previously healthy, white Lebanese female patient who presented with forgetfulness, unsteady gait, right-sided motor weakness, and dysphagia. She was found to have an anaplastic meningioma located in the left parietal lobe that was treated by surgical resection. The patient had an uneventful postoperative course, and was stable at later follow-ups. CONCLUSIONS This case report describes the clinical presentation, pathological findings, and the prognosis of this mass, which is atypical in this location, and has been rarely reported in the literature. We also review the literature on anaplastic meningiomas.

Understanding and predicting the impact of critical dissolution variables for nifedipine immediate release capsules by multivariate data analysis.

In this study the selection of in vivo predictive in vitro dissolution experimental set-ups using a multivariate analysis approach, in line with the Quality by Design (QbD) principles, is explored. The dissolution variables selected using a design of experiments (DoE) were the dissolution apparatus [USP1 apparatus (basket) and USP2 apparatus (paddle)], the rotational speed of the basket/or paddle, the operator conditions (dissolution apparatus brand and operator), the volume, the pH, and the ethanol content of the dissolution medium. The dissolution profiles of two nifedipine capsules (poorly soluble compound), under conditions mimicking the intake of the capsules with i. water, ii. orange juice and iii. an alcoholic drink (orange juice and ethanol) were analysed using multiple linear regression (MLR). Optimised dissolution set-ups, generated based on the mathematical model obtained via MLR, were used to build predicted in vitro-in vivo correlations (IVIVC). IVIVC could be achieved using physiologically relevant in vitro conditions mimicking the intake of the capsules with an alcoholic drink (orange juice and ethanol). The multivariate analysis revealed that the concentration of ethanol used in the in vitro dissolution experiments (47% v/v) can be lowered to less than 20% v/v, reflecting recently found physiological conditions.

An in vitro-in vivo correlation study for nifedipine immediate release capsules administered with water, alcoholic and non-alcoholic beverages: Impact of in vitro dissolution media and hydrodynamics.

The impact of hydrodynamics and media composition on nifedipine dissolution profile from IR (immediate release) soft capsules was investigated using dissolution apparatus USP1, USP2, USP3 and USP4 (United State Pharmacopoeia). Media composition was varied in terms of pH and content, to mimic the dosage form intake with water or non-alcoholic beverages (orange juice) and alcoholic beverages (orange juice/ethanol mixture (47% v/v)). Through construction of in vitro-in vivo correlations (IVIVC) with corresponding in vivo data from the literature, it was possible to evaluate the in vitro conditions that are likely to simulate the in vivo formulation behaviour. Both linear and nonlinear correlations were obtained depending on experimental set-ups. Testing of 20mg nifedipine capsules in FaSSGFst (Fasted State Simulated Gastric Fluid pH 1.6; water administration) produced IVIVC with the USP3 (after time scaling) and USP4 apparatus. IVIVC were obtained for USP2, USP3 and USP4 in FaSSGFoj (Fasted State Simulated Gastric Fluid pH 3.4; orange juice administration). Linear and nonlinear correlations were obtained with the USP1, USP2 and USP3 apparatus when testing the capsules in FaSSGFoj/EtOH (orange juice/ethanol administration). This study highlighted that selection of physiologically relevant dissolution set-ups is critical for predicting the in vivo impact of formulations co-administration with water, non-alcoholic and alcoholic beverages.

Identification of phenotypic markers of B cells from patients with Chagas disease.

Chagas disease was discovered more than a hundred years ago, but its pathogenesis is still not completely understood. Autoimmunity is one of the mechanisms shown to contribute to its pathogenesis, which may indicate an important participation of B lymphocytes. Patients with Chagas disease have shown increased percentage of B cells producing IL-10. However, there are no reports of the phenotypic markers of B cells producing IL-10 in patients with Chagas disease. For the first time in the literature, we evaluated the phenotypic profile of distinct markers of B cells from peripheral blood of noninfected individuals and patients with Chagas disease. Our results showed that patients with Chagas disease had a higher expression of CD21 and CD24 on the surface of CD19+ B cells, while CD43 and CD23 were expressed equally in all groups. Moreover, the expression of MHC-II (HLA-DR), CD80, CD86, caspase-3, granzyme B and intracellular IL-10 and TGF-ß by CD19+ B cells was higher in patients with Chagas disease. The results of IL-10 production within CD19+ CD5+ CD1d+ B cells showed a higher percentage of this cytokine in patients with Chagas disease. Thus, our data bring a new knowledge about distinct markers of B cells in immune responses of Chagas disease.

Characterization of CD4⁺ cytotoxic lymphocytes and apoptosis markers induced by Trypanossoma cruzi infection.

Although the pathophysiology of Chagas disease is not completely understood, it is widely accepted that involvement of the immune response is critical in determining the outcome of the disease. In this context, CD4⁺ T cells may play an important role in generating different mechanisms of protection. In addition to effector and regulatory functions, CD4⁺ T cells may be also involved with lytic activities against the parasite and may have a relevant role on control of the infection. In this study, we have evaluated CD4⁺ T cells expressing cytotoxic and apoptosis markers in response to Trypanossoma cruzi infection in indeterminate (IND) and cardiac (CARD) patients with Chagas disease and non-infected individuals (NI). Our data demonstrated that: (1) CD4⁺ T cells presented higher ex vivo granzyme B expression in patients with Chagas disease compared with healthy individuals and that antigen induced a greater granzyme B expression in IND patients; (2) CD95L expression in CD4⁺ CD95⁺ T cells from IND patients is higher than in CARD and NI; (3) IND and CARD patients had an increased frequency of caspase-3 after in vitro stimulation and also expressed a high frequency of annexinV⁺ 7ADD⁺ within CD4⁺ T cells; (4) Lastly, a positive correlation was seen between cytotoxic molecules and CD45RO memory marker in CD4⁺ T cells and between caspase-3 and CD95L within CD4⁺ CD95⁺ T cells. These results suggest new insights into the functional competence of CD4⁺ T cells among the different clinical forms of Chagas disease, which will lead to a better understanding of their influence during immune responses against T. cruzi.

Foxp3+CD25(high) CD4+ regulatory T cells from indeterminate patients with Chagas disease can suppress the effector cells and cytokines and reveal altered correlations with disease severity.

Immunoregulatory mechanisms are important to control the intense immune activity induced in Chagas disease. We evaluated the phenotypic profile and the mechanisms by which Treg cells function in patients with the indeterminate (IND) and cardiac (CARD) clinical forms of Chagas disease. The frequency of Foxp3(+)CD25(high) CD4(+)-T cells is augmented and correlated with the maintenance of a better cardiac function in IND. Treg cells from IND present suppressive activity, although the mechanism is not IL-10 or CTLA-4 dependent and are able to produce augmented levels of IL-17, IL-10 and granzyme B being its frequency correlated with percentage of Annexin V(+) CD4(+)-cells. In contrast, CARD presents higher frequency of IL-6(+), IFN-gamma(+), TNF-alpha(+) and CTLA-4(+) Treg-cells than IND. Thus, our data suggest that Treg cells have an important role in controlling the exacerbated immune response and morbidity in Trypanosoma cruzi infection, probably modulating the cytokine environment and/or killing effector cells.

Distributions of total skin surface area to body weight ratios for use in dermal exposure assessments.

Surface area to body weight ratios were calculated for three age groups of the population using direct measurement data reported in the scientific literature. A strong negative correlation was observed between these ratios and age, and ratios did not differ as a function of sex. Distribution data for surface area to body weight ratios are presented for three age groups. Because of the strong correlation between these two factors, the use of these distributions in human exposure/risk assessments using point estimation techniques and/or Monte Carlo simulations may be more appropriate than treating surface area and body weight as independent variables.

[Experimental studies on the therapeutic modification of intestinal adhesion formation]. / Experimentelle Untersuchungen zur therapeutischen Beeinflussbarkeit intestinaler Adhäsionsvorgänge.

One of the main problems encountered by the surgeon are visceral adhesions after abdominal surgery. This problem was studied in animal experiments by inducing peritoneal adhesions in 30 albino rats. The anti-inflammatory, resp. anti-adhesive effect of corticosteroids and antihistamines was tested by application of these drugs before, resp. after surgery. Anti-inflammatory proteolytic enzymes (Wobe-Mugos) were applied pre-, resp. postoperatively in two other groups. A fifth group served as controls. A modified cotton-pellet technique was used for the experiments. The best results were achieved when "Wobe-Mugos" was applied after surgery.

Chronic cyanide exposure: a clinical, radioisotope, and laboratory study.

The effect of chronic cyanide exposure in the electroplating sections of three factories employing 36 workers was studied and compared with a control group. The concentration of cyanides to which the workers were exposed was measured. The regression line showing the relationship between thiocyanates in urine and the concentration of cyanides in the air was plotted. Increased percentages of haemoglobin and lymphocyte count were present in all exposed workers, in addition to punctate basophilia in 28 workers. Cyanmethaemoglobin was found to be characteristic. Apart from other complaints, two men with psychosis similar to one case reported in therapeutic thiocyanate intoxication were found. Twenty of the workers had thyroid enlargements to a variable degree and consistency, in two of whom it resembled lymphadenoid goitre. Thyroid 131I uptakes at 4 and 24 hours were significantly higher than in the controls, while 131PBI was unchanged. The reason for this iodine deficiency-like action is discussed.

A field survey on child health in a rural community in Egypt.

A field survey in a village was carried out to study child health in a rural area. The vaccination scheme was found to be inadequate and the value of health education is stressed. Parasitic infestation was found to be higher than urban areas but significantly lower than 1959 and the latter is attributed to a safer water supply. Growth and development lagged behing the whole national standards particularly during the 1 - 6 years age period. Health care for the pre-school age, taking advantage of co-operation from medical faculties and local health authorities, is recommended.