Comparison of the Latin America Regulation Landscape and International Reference Health Authorities to Hasten Drug Registration and Clinical Research Applications.

Introduction: Promptly providing new drugs to fulfill unmet medical needs requires changes in drug development and registration processes. Health Authorities (HAs) considered as reference due to their experience and acknowledgement (Food and Drug Administration [FDA] among others) already consider innovative clinical trial (CT) designs and flexible approval procedures, but Latin America (LATAM) regulations are still far. A comparison was performed to identify gaps.

Mechanisms of regenerative preconditioning in pigs with subtotal hepatectomies.

Background: Portal vein occlusion shortly before extended hepatic resections has hepatoprotective properties, but its molecular effects have not been elucidated. We characterized the impact of regenerative preconditioning by portal vein embolization (PVE) on hepatic energy metabolism and cytokine expression.

Materials And Methods: About 90% hepatectomies were performed in normal pigs (Control) and in pigs that underwent a PVE 24 h before the surgery (n = 10/group).

Hepatic flow is an intraoperative predictor of early allograft dysfunction in whole-graft deceased donor liver transplantation: An observational cohort study.

Background: Early allograft dysfunction (EAD) after liver transplantation (LT) is an important cause of morbidity and mortality. To ensure adequate graft function, a critical hepatocellular mass is required in addition to an appropriate blood supply. We hypothesized that intraoperative measurement of portal venous and hepatic arterial flow may serve as a predictor in the diagnosis of EAD.

Comprehensive Characterization of a Porcine Model of The "Small-for-Flow" Syndrome.

Introduction: The term "Small-for-Flow" reflects the pathogenetic relevance of hepatic hemodynamics for the "Small-For-Size" syndrome and posthepatectomy liver failure. We aimed to characterize a large-animal model for studying the "Small-for-Flow" syndrome.

Methods: We performed subtotal (90%) hepatectomies in 10 female MiniPigs using a simplified transection technique with a tourniquet.

Donor Risk Index Has an Impact in Intraoperative Measure of Hepatic Artery Flow and in Clearance of Indocyanine Green: An Observational Cohort Study.

Background: The increase in indications for liver transplantation has led to acceptance of donors with expanded criteria. The donor risk index (DRI) was validated with the aim of being a predictive model of graft survival based on donor characteristics. Intraoperative arterial hepatic flow and indocyanine green clearance (plasma clearance rate of indocyanine green [ICG-PDR]) are easily measurable variables in the intraoperative period that may be influenced by graft quality.

Are high-sensitivity troponins always reliable? Donor-recipient troponin transfusion in liver transplantation.

Blood troponins are used to diagnose perioperative myocardial injury and infarction. During liver transplantation, a passive donor-recipient troponin transfer with the graft may result in an increase of troponins in the transplant recipient questioning the diagnosis of myocardial injury. We present a case of liver transplantation with sudden elevation of recipient's serum troponin levels immediately after graft reperfusion and its subsequent normalization in which myocardial damage and other non-ischaemic potential causes were ruled out.

Epidemiological Study of Carbon Monoxide Deaths in Scotland 2007-2016.

Carbon monoxide (CO) intoxications are quite frequent in forensic toxicology. Using a sample of 209 CO-positive deaths in Scotland from 2007 to 2016, this study provides ranges of percentage CO saturations (%COHb) according to the CO source and examines any correlation with age, gender, alcohol, and preexisting disease. It also reports the full toxicological findings, including drug concentrations, in CO-positive cases.

Preconditioning by portal vein embolization modulates hepatic hemodynamics and improves liver function in pigs with extended hepatectomy.

Background: Portal vein embolization is performed weeks before extended hepatic resections to increase the future liver remnant and prevent posthepatectomy liver failure. Portal vein embolization performed closer to the operation also could be protective, but worsening of portal hyper-perfusion is a major concern. We determined the hepatic hemodynamic effects of a portal vein embolization performed 24 hours prior to hepatic operation.

Early Measurement of Indocyanine Green Clearance Accurately Predicts Short-Term Outcomes After Liver Transplantation.

Background: There are no accurate tools to predict short-term mortality or the need for early retransplantation after liver transplantation (LT). A noninvasive measurement of indocyanine green clearance, the plasma disappearance rate (PDR), has been associated with initial graft function.

Methods: We evaluated the ability of PDR to predict early mortality or retransplantation after LT.

Positive influence of a natural product as propolis on antioxidant status and lipid peroxidation in senescent rats.

Given the importance of oxidative stress associated to aging, it would be interesting to assess the effect of oral supplementation with antioxidant substances capable of diminishing oxidative aggression and free radicals generation associated to this condition. This study investigated the effects of AIN-93 M diet supplemented either with 2 % of propolis, or with 4 % of a natural product obtained from lyophilizate vegetables, selected by its antioxidant properties, in senescent healthy Wistar rats fed ad libitum over 3 months. Propolis supplementation leads to a lower level of glucose and cholesterol concentrations together with a reduction in protein oxidation.

[Prevalence of renal artery stenosis in patients with critical limb ischemia].

Background And Objective: Our purpose was to evaluate the prevalence of renal artery stenosis in patients with critical limb ischemia and to study any clinical or laboratory indicator that could predict this association.

Patients And Method: One hundred consecutive patients with critical limb ischemia evaluated by angiogram were included in the study from January to July 2003. Cardiovascular risk factors and renal function were analyzed.

COT kinase proto-oncogene expression in T cells: implication of the JNK/SAPK signal transduction pathway in COT promoter activation.

COT/Tpl-2 proto-oncogene encodes a serine/threonine kinase implicated in cellular activation. In this study we have identified the human COT gene promoter region and three different human COT transcripts. These transcripts, with the same initiation site, display heterogeneity in their 5' untranslated regions and in their subcellular localization.

Chronic traumatic pseudoaneurysm of right subclavian artery.

A right subclavian artery pseudoaneurysm caused by blunt trauma is described. CT and digital subtraction angiography helped us to establish a correct diagnosis. Radiologic features of subclavian artery aneurysms and relevant literature are briefly discussed.

Regulation of ERK2 dephosphorylation in G1-stimulated rat T lymphoblasts.

Rat T lymphoblasts arrested in the G1 phase of the cell cycle by interleukin-2 (IL-2) deprivation can be forced to proceed to the S phase when they are stimulated with IL-2 or the phorbol ester phorbol 12,13-dibutyrate (PDBu). When PDBu is used as a stimulus, extracellular regulated kinase 2 (ERK2) is activated by threonine and tyrosine phosphorylation by the dual-specificity kinase MEK. Here we have studied the regulation of ERK2 dephosphorylation as a mechanism for inactivation of this kinase.

Cot kinase regulation of IL-2 production in Jurkat T cells.

tpl-2 is a rat gene that encodes a serine/threonine protein kinase that can act as a novel mitogen-activated protein (MAP) kinase kinase kinase. Tpl-2 is activated in Moloney murine leukemia virus-induced rat T lymphomas, due to a truncation in the C-terminal region of the protein. cot is a very closely related gene, if not the human homologue.

Raf-1 and ERK2 kinases are required for phorbol 12,13-dibutyrate-stimulated proliferation of rat lymphoblasts. ERK2 activation precedes Raf-1 hyperphosphorylation.

Rat lymphoblasts are arrested in the G1 phase of the cell cycle and can be promoted to proceed up to the S phase, when they are stimulated by phorbol ester. In this work, we have studied some details of the phorbol 12,13-dibutyrate (PBu2)-stimulated proliferation. We show that in response to PBu2 at least four different protein kinase C (PKC) isoforms translocate to the membrane.

[Surgical wound infection in patients undergoing extra-anatomical arterial surgery. A retrospective study].

We present a retrospective review of a series of patients from our Service submitted to surgical extra-anatomical grafts. Correlation between diverse variants and ulterior obliteration by thrombosis or infection of the surgical wounds is analyzed. The series included 133 patients surgically treated between 1986 and 1991.

[Complete reconstructions without intermediate anastomoses].

Results from 9 complete reconstructions without intermediate anastomosis (8 patients) are presented. In five cases a by-pass from femoral artery to the contralateral popliteal (infra or supra-rotuliar) arterial prosthesis was performed. In other case a by-pass from the aorta artery to the third popliteal section was placed.

[Arteriovenous fistulae of posttraumatic origin: apropos 7 cases].

We present our experience with arterio-venous traumatic fistulas. Seven cases, between 6 patients are reviewed. Respective etiologies were: 4 cases after an accidental traumatism, 2 cases produced by iatrogenicity and 1 case of idiopathic etiology.

[Heparin-induced hemorrhage in the treatment of venous thromboembolism].

Retrospective study about the frequency of hemorrhagic complications (258 patients) in the treatment of venous thrombosis and/o pulmonary embolism, with heparin. Heparin was intermittently administered by endovenous way and controlled during the ten first days. Mostly of the big hemorrhages happened between the seventh and the tenth day, in digestive and urinary system mainly.

[Compression of the iliac vein and occult neoplasm].

Three cases demonstrating the possible venous system compression by some neoplasias, feigning an nonexistent thrombosis, are presented. Author stands out the fitness of to investigate possible neoplasias in thrombosis without apparent causality.

Aneurysm of the inferior mesenteric artery.

A case of arteriosclerotic aneurysm of the inferior mesenteric artery, in which obliteration of both the coeliac axis and the superior mesenteric artery was found by chance in a patient with chronic ischaemia of the lower extremities and without digestive vascular trouble is reported. The surgical treatment is discussed and the reasons for its applications analysed. A review of world literature revealed only two previously published cases, which are quoted.