A Focus on the Pathophysiology of Adrenomedullin Expression: Endothelitis and Organ Damage in Severe Viral and Bacterial Infections.

Adrenomedullin (ADM) is a peptide hormone produced primarily in the adrenal glands, playing a crucial role in various physiological processes. As well as improving vascular integrity and decreasing vascular permeability, ADM acts as a vasodilator, positive inotrope, diuretic, natriuretic and bronchodilator, antagonizing angiotensin II by inhibiting aldosterone secretion. ADM also has antihypertrophic, anti-apoptotic, antifibrotic, antioxidant, angiogenic and immunoregulatory effects and antimicrobial properties. ADM expression is upregulated by hypoxia, inflammation-inducing cytokines, viral or bacterial substances, strength of shear stress, and leakage of blood vessels. These pathological conditions are established during systemic inflammation that can result from infections, surgery, trauma/accidents or burns. The ability to rapidly identify infections and the prognostic, predictive power makes it a valuable tool in severe viral and bacterial infections burdened by high incidence and mortality. This review sheds light on the pathophysiological processes that in severe viral or bacterial infections cause endothelitis up to the development of organ damage, the resulting increase in ADM levels dosed through its more stable peptide mid-regional proadrenomedullin (MR-proADM), the most significant studies that attest to its diagnostic and prognostic accuracy in highlighting the severity of viral or bacterial infections and appropriate therapeutic insights.

SUPERFÍCIE DE IMPLANTES DE TITÂNIO E SUA CAPACIDADE DE ESTÍMULO NA FORMAÇÃO ÓSSEA: UMA REVISÃO DE LITERATURA / Surface of Titanium Implants and your Ability to Stimulate Bone Formation: A Review of Literature

Durante anos o grande desafio da odontologia tem sido a busca por métodos que reabilitem os pacientes de forma menos traumática e eficaz do ponto de vista funcional e estético. Nessa interface, os implantes dentários surgiram e estão em pleno desenvolvimento tecnológico para garantir a satisfação dos pacientes. Dessa forma, o objetivo deste trabalho foi revisar a literatura sobre as superfícies de implantes de titânio e sua capacidade de estimulo na formação óssea, enfocando evidências científicas acerca das alterações químicas e topográficas no contexto da osseointegração.

For years the big challenge of dentistry has been the search for methods that rehabilitates patients less traumatic, and more effective functionally and aesthetically. In this interface, dental implants have emerged and are being increasingly perfected to ensure the complete satisfaction of rehabilitated patients. Thus, the aim of this study was to develop a theoretical review on the surfaces of titanium implants and their ability to stimulate bone formation focusing on scientific evidence of chemical and topographical changes in the context of osseointegration.

A long-term retrospective review of 5 cases using daptomycin for prosthetic device infections after surgery.

PURPOSE: To review the antimicrobial possibilities for limb-sparing due to infectious complications after surgery in patients diagnosed with osteosarcoma and with implantation of prosthetic devices. PATIENTS AND PROGRESS: After several episodes of relapsing infection or even re-infection and failure of previous therapies, 5 patients (2 young, female / 1 young, male / 2 middle-aged, female) were subject to a long-term ambulatory regimen consisting of intravenous administration of daptomycin. RESULTS: Showed improved outcome with preservation of the limbs or devices involved. CONCLUSION: Five patients with post-operative gram-positive suspected infections of prosthetic devices that were unresponsive to a variety of other antibiotics and combinations appeared to respond to compassionate use of daptomycin. its effectiveness is probably due to its activity against biofilmproducing microorganisms. Controlled, double-blind randomized trials are needed to confirm the potential of daptomycin in such patients.

Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas.

PURPOSE: To evaluate the feasibility and safety of intratumoral injection of autologous dendritic cells (DCs) transfected with an adenovirus encoding interleukin-12 genes (AFIL-12) for patients with metastatic gastrointestinal carcinomas. Secondarily, we have evaluated biologic effects and antitumoral activity. PATIENTS AND METHODS: Seventeen patients with metastatic pancreatic (n = 3), colorectal (n = 5), or primary liver (n = 9) malignancies entered the study. DCs were generated from CD14+ monocytes from leukapheresis, cultured and transfected with AFIL-12 before administration. Doses from 10 x 10(6) to 50 x 10(6) cells were escalated in three cohorts of patients. Patients received up to three doses at 21-day intervals. RESULTS: Fifteen (88%) and 11 of 17 (65%) patients were assessable for toxicity and response, respectively. Intratumoral DC injections were mainly guided by ultrasound. Treatment was well tolerated. The most common side effects were lymphopenia, fever, and malaise. Interferon gamma and interleukin-6 serum concentrations were increased in 15 patients after each treatment, as well as peripheral blood natural killer activity in five patients. DC transfected with AFIL-12 stimulated a potent antibody response against adenoviral capsides. DC treatment induced a marked increase of infiltrating CD8+ T lymphocytes in three of 11 tumor biopsies analyzed. A partial response was observed in one patient with pancreatic carcinoma. Stable disease was observed in two patients and progression in eight patients, with two of the cases fast-progressing during treatment. CONCLUSION: Intratumoral injection of DC transfected with an adenovirus encoding interleukin-12 to patients with metastatic gastrointestinal malignancies is feasible and well tolerated. Further studies are necessary to define and increase clinical efficacy.