Synthesis and Antimicrobial Screening of Pyrazolo-3-Aryl Quinazolin-4(3H)ones

2-thio-3-aryl quinazolin-4(3H)one (1) was synthesized by reacting anthranilic acid with thiocarbamate salts of substituted aniline and carbon disulphide, which on reflux with excess of hydrazine hydrate to form 2-hydrazino quinazolin-4(3H)one derivatives (2). The reaction of (2) with variously substituted aryl aldehydes gave the corresponding hydrazones (3). Further, the cyclization of compound (3) in acetic anhydride gave tricyclic pyrazoloquinazolinones (4). All newly synthesized compounds have been tested for their antibacterial activity against gram +ve bacteria B. substilis, S. aureus and gram –ve bacteria E. coli, P. vulgaris. The species used for antifungal activity are Aspergillus niger and Phytophora. Introduction of -OCH3, -OH and -Cl groups to the heterocyclic frame work enhanced antibacterial and antifungal activities

Esclerose lateral amiotrófica e herpes vírus. Relato de um caso curioso: uma associação casual ou causal? Amyotrophic lateral sclerosis and herpes virus. A curious case report: a cause or casual association?

OBJETIVO: Apresentar o relato de um caso curioso de esclerose lateral amiotrófica (ELA). CASO: Homem de 47 anos que apresentava déficit de força nos membros superiores evoluindo há 4 anos. A eletroneuromiografia era compatível a ELA, forma de Vulpian-Bernardt. O estudo do líquido cefalorraqueano (LCR) mostrava processo inflamatório e positividade das reações para Herpes vírus I e II. O estudo do LCR, do soro sanguíneo e da barreira hemato-encefálica sugeria imunoprodução local para Herpes vírus tipo I. A ressonância nuclear magnética sugeria mielopatia cística ou seringomielia em medula cervical estendendo-se nos espaços C2 a C4. O paciente foi tratado com aciclovir endovenoso por 21 dias. Até dois meses após, o paciente não foi submetido a novos exames subsidiários para controle. DISCUSSÃO: Até o momento atual, a doença ELA não tem tratamento medicamentoso específico. A noção da existência de "síndrome esclerose lateral amiotrófica" associada a etiologias diversas pode contribuir para o tratamento de alguns doentes.<br>OBJECTIVE: To present a curious case of amyotrophic lateral sclerosis (ALS). CASE: A forty-seven year old man claimed of paresis in the arms since four years. The electrical study of the muscles and nerves diagnosis was ALS, type Vulpian-Bernardt. The cerebrospinal fluid study revealed an inflammatory process and the positivity of immulogical reactions for Herpes simplex I. The blood-brain barrier study showed the possibility that immulogical response for Herpes simplex I was produced in the spinal fluid space. A magnetic resonance suggested cystic myelopathy of cervical spinal cord expanding from C2 to C4. The patient received endovenous acyclovir for 21 days. Until two months after the medication we did not submit the patient to other subsidiary examinations. DISCUSSION: Until now there is no specific drug treatment for ALS. The notion that there is a "syndrome of ALS" related with various causes may help to treat some patients

CCL2 disrupts the adherens junction: implications for neuroinflammation

Alterations to blood-brain barrier (BBB) adhesion molecules and junctional integrity during neuroinflammation can promote central nervous system (CNS) pathology. The chemokine CCL2 is elevated during CNS inflammation and is associated with endothelial dysfunction. The effects of CCL2 on endothelial adherens junctions (AJs) have not been defined. We demonstrate that CCL2 transiently induces Src-dependent disruption of human brain microvascular endothelial AJ. β-Catenin is phosphorylated and traffics from the AJ to PECAM-1 (platelet endothelial cell adhesion molecule-1), where it is sequestered at the membrane. PECAM-1 is also tyrosine-phosphorylated, an event associated with recruitment of the phosphatase SHP-2 (Src homology 2 domain-containing protein phosphatase) to PECAM-1, β-catenin release from PECAM-1, and reassociation of β-catenin with the AJ. Surface localization of PECAM-1 is increased in response to CCL2. This may enable the endothelium to sustain CCL2-induced alterations in AJ and facilitate recruitment of leukocytes into the CNS. Our novel findings provide a mechanism for CCL2-mediated disruption of endothelial junctions that may contribute to BBB dysfunction and increased leukocyte recruitment in neuroinflammatory diseases