Vasodilators in Septic Shock Resuscitation: A Clinical Perspective

ABSTRACT: Microcirculatory abnormalities have been shown to be frequent in patients with septic shock despite “normalization” of systemic hemodynamics. Several studies have explored the impact of vasodilator therapy (prostacyclin, inhaled nitric oxide, topic acetylcholine and nitroglycerin) on microcirculation and tissue perfusion, with contradictory findings.In this narrative review, we briefly present the pathophysiological aspects of microcirculatory dysfunction, and depict the evidence supporting the use of vasodilators and other therapeutic interventions (fluid administration, blood transfusion, vasopressors and dobutamine) aiming to improve the microcirculatory flow in septic shock patients

Mutation and genomic amplification of the PIK3CA proto-oncogene in pituitary adenomas

The tumorigenesis of pituitary adenomas is poorly understood. Mutations of the PIK3CA proto-oncogene, which encodes the p110-α catalytic subunit of PI3K, have been reported in various types of human cancers regarding the role of the gene in cell proliferation and survival through activation of the PI3K/Akt signaling pathway. Only one Chinese study described somatic mutations and amplification of the PIK3CA gene in a large series of pituitary adenomas. The aim of the present study was to determine genetic alterations of PIK3CA in a second series that consisted of 33 pituitary adenomas of different subtypes diagnosed by immunohistochemistry: 6 adrenocorticotropic hormone-secreting microadenomas, 5 growth hormone-secreting macroadenomas, 7 prolactin-secreting macroadenomas, and 15 nonfunctioning macroadenomas. Direct sequencing of exons 9 and 20 assessed by qPCR was employed to investigate the presence of mutations and genomic amplification defined as a copy number ≥4. Previously identified PIK3CA mutations (exon 20) were detected in four cases (12.1%). Interestingly, the Chinese study reported mutations only in invasive tumors, while we found a PIK3CA mutation in one noninvasive corticotroph microadenoma. PIK3CA amplification was observed in 21.2% (7/33) of the cases. This study demonstrates the presence of somatic mutations and amplifications of the PIK3CA gene in a second series of pituitary adenomas, corroborating the previously described involvement of the PI3K/Akt signaling pathway in the tumorigenic process of this gland

Reduction of SARS-CoV-2 viral load in saliva after rinsing with mouthwashes containing cetylpyridinium chloride: a randomized clinical study

Background Symptomatic patients with COVID-19 typically have a high SARS-CoV-2 viral load in their saliva. Procedures to reduce the viral load in their oral cavity are important for mitigating the viral transmission. Methods This randomized clinical trial investigated the impact of two mouthwashes (0.075% cetylpyridinium chloride plus 0.28% zinc lactate (CPC+Zn) (n = 32), and 0.075% cetylpyridinium chloride (CPC) (n = 31)) on the viral load of SARS-CoV-2 in saliva when compared to the distilled water negative control (n = 32). Saliva was collected before (T0) and after (5 min, T1; 30 min, T2; and 60 min, T3) the intervention. Viral load in saliva was measured by qRT-PCR assays. The data in both groups was normalized for T0 and Negative Control, resulting in fold change values. Results CPC+Zn oral solution reduced the viral load in saliva by 6.34-fold at T1, 3.6-fold at T2 and 1.9-fold at T3. Rinsing with the CPC mouthwash reduced the viral load in saliva by 2.5-fold at T1, 1.9-fold at T2 and 2.0-fold at T3. Conclusion CPC+Zn mouthwash or with the CPC mouthwash reduced the viral load in saliva of COVID-19 patients immediately after rinsing. These reductions extended up to 60 min