Modelling of the blood-brain barrier in drug discovery and development

The market for neuropharmaceuticals is potentially one of the largest sectors of the global pharmaceutical market owing to the increase in average life expectancy and the fact that many neurological disorders have been largely refractory to pharmacotherapy. The brain is a delicate organ that can efficiently protect itself from harmful compounds and precisely regulate its microenvironment. Unfortunately, the same mechanisms can also prove to be formidable hurdles in drug development. An improved understanding of the regulatory interfaces that exist between blood and brain may provide novel and more effective strategies to treat neurological disorders.     

Morphometric analysis,region of supply and microanatomy of the lenticulostriate arteries and their clinical significance

The lenticulostriate arteries (LSA) and their microanatomy, region of supply and atherosclerosis were examined in 24 microdissected brains, arterial casts, and histological specimens. The LSA ranged from 2 to 12 in number and from 0.10 mm to 1.28 mm in diameter. They always arose from the initial segment of the middle cerebral artery (MCA), often from the MCA leptomeningeal branches (38.24%), and rarely from the insular segment (2.94%). They always originated as individual branches, often (61.76%) with their own common stems. In two hemispheres we found that the LSA supplied either a larger or a smaller portion of the basal ganglia and internal capsule than usual. The number of twigs to the innominate substance (substantia innominata) (3–11), and their diameters (0.07–0.30 mm), has been described for the first time, to our knowledge. Microatheromas were found in two LSA. Data about the LSA microanatomy and territory could form the basis of safer neurosurgery, more accurate neuroimaging evaluation, and precise neurological diagnosis in patients with focal ischemic lesions in the basal ganglia and internal capsule.     

MDR1 gene polymorphism: therapeutic response to paroxetine among patients with major depression

The multidrug resistance transporter, P-glycoprotein (P-gp), encoded by polymorphic MDR1 (ABCB1) gene, is involved in efflux transport of several antidepressants and acts as a barrier to different exogenous noxa in the blood-brain barrier. MDR1 gene belongs to the best understood mediators of drug resistance. Different polymorphisms in MDR1 have been found to be connected with P-gp expression and function. The aims of the study were to investigate the potential influence of MDR1 polymorphisms, exon 26 C3435T and exon 21 G2677T/A, on treatment response to paroxetine (20 mg/day) in patients with major depression. To assess and evaluate therapeutic response to paroxetine, all patients were rated weekly using the HAMD-17 scale. Responders were defined as subjects with a decrease in HAMD scale by >or=50% at week 6 of treatment. The study population included 127 patients with major depression (diagnosed by Structured Clinical Interview for DSM-IV disorders). Our results indicated that MDR1 variants G2677T and C3435T are not associated with therapeutic response to paroxetine in patients with major depressive disorder. The associations between paroxetine and P-glycoprotein still need to be clarified.     

Severity of COVID-19 Symptoms among University of Belgrade Students during the July–September 2021 Pandemic Wave: Implications for Vaccination

ObjectiveThe aim of this study was to identify the intensity of COVID-19 symptoms during the pandemic wave during July–September 2021 and to identify factors associated with having moderate and severe symptoms of COVID-19 among affected students in the University of Belgrade.Material and MethodsThis study was carried out at the Institute for Students'' Health (ISH) in Belgrade, Serbia. The ISH is the referral institution for health care delivery at primary and secondary levels. This analysis includes students who presented from July 1 until September 30, 2021, when the latest pandemic wave of COVID-19 was observed among university students. Data were extracted from students'' electronic medical records. Three levels of COVID-19 symptom intensity were defined: mild, moderate, and severe.ResultsOf students seeking medical care at the ISH who were diagnosed with COVID-19, 27.3% had mild disease and the majority, 59.3%, had moderate disease, and 13.4% had severe symptoms. Of all students, 124 (21.8%) were fully vaccinated with 2 doses of Sinopharm (81, 60.9%), Pfizer-BioNTech (38, 28.6%), Sputnik V (7, 5.3%), or the Oxford-AstraZeneca vaccine (7, 5.3%). The multiple multinomial regression model suggests that students who were vaccinated against COVID-19 were 78% less likely to develop moderate symptoms and 96% less likely to develop severe symptoms of COVID-19.ConclusionStudents who are vaccinated against COVID-19 are at lower risk of developing moderate and severe symptoms of the disease.     

Risk Factors for Surgery in Pediatric Patients with Crohn's Disease

ObjectivePediatric Crohn''s disease (CD) has a more aggressive phenotype and course than in adults. Many patients develop complications that require surgery. The aim of this study was to identify the factors associated with increased risk for surgical intervention in pediatric patients with CD.Subjects and MethodsThis study is a retrospective review of medical records. We analyzed the following variables: sex, age at diagnosis, presenting symptoms, duration of symptoms before diagnosis, disease location and severity, the presence of extraintestinal manifestations, and the presence of anti-Saccharomyces cerevisiae antibodies. Univariate analysis using the Mann-Whitney test and Fisher''s exact test was performed to detect the factors associated with surgery. Potential risk factors with p < 0.05 were further analyzed using a multivariate binary logistic regression model.ResultsFifty-seven patients (27 girls and 30 boys) were included in the analysis. More than one-fourth of them (28.1%) required surgical management. Female sex (p = 0.043), disease behavior (p = 0.012), and the presence of perianal disease at diagnosis (p < 0.001) were the variables associated with surgical intervention. Stricturing disease (B2) (odds ratio [OR], 24.944; p = 0.016), stricturing and penetrating disease (B2B3) (OR, 28.276; p = 0.011), and the presence of perianal disease at diagnosis (OR, 95.802; p = 0.001) were independent risk factors for surgery. Female sex was associated with surgery without being an independent risk factor.ConclusionFemales with B2 or B2B3 or the presence of perianal disease at diagnosis are at a higher risk for surgery and should be considered for more aggressive medical treatments.     

The Erector Spinae Plane Block as Novel Therapy for Renal Colic

We present a 10-patient case series supporting the use of the erector spinae plane block (ESPB) as a novel approach for the treatment of acute pain from renal colic. An in-plane needle approach was used with either transverse or longitudinal orientation of the ultrasound probe on the affected side, in either seated or prone patient position. These cases showed significant improvement in patient reported pain; suggesting that the ESPB can be used safely and effectively for either primary or adjunctive treatment of acute pain due to renal colic in the emergency department.