Search

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA., Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up., Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections., Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception., (© 2024. The Author(s).)

ACTH signaling pathway includes the action of both protein kinases, mainly cAMP-dependent protein kinase (protein kinase A, PKA), and serine/threonine and tyrosine phosphatases. MAPK phosphatase-1 (MKP-1) is a dual activity protein phosphatase involved in the dephosphorylation of MAPK. To determine whether MKP-1 is a component of ACTH cascade, here we investigate the expression levels of MKP-1 gene in Y1 mouse adrenocortical tumor cells under ACTH stimulation. ACTH transiently increased MKP-1 mRNA and protein levels. MKP-1 mRNA increase occurred at 30 min, peaked at 1 h (6-fold), and returned to basal levels thereafter. The ACTH-mediated mRNA increase was blunted by actinomycin D and enhanced by cycloheximide. A cell permeable cAMP analog, 8-bromo-cAMP, also transiently induced MKP-1 mRNA (4-fold) and the PKA inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamid abolished this effect. In contrast, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamid only partially reduced the effect of ACTH, suggesting the participation of PKA-independent mechanisms in the hormone-induced MKP-1 expression. In addition, we show that the rise in intracellular Ca(2+) and protein kinase C activation had a potent synergic effect on ACTH- and 8-bromo-cAMP-mediated MKP-1 induction. In summary, our findings demonstrate that MKP-1 is another component of ACTH signaling cascade and indicate that this hormone may potentially down-regulate MAPKs.

We have previously purified and cloned a phosphoprotein, Arachidonic acid-Related Thioesterase Involved in Steroidogenesis (ARTISt), involved in steroid synthesis through Arachidonic Acid (AA) release. Arachidonic acid-related thioesterase involved in steroidogenesis resulted to be a member of a new family of acyl-CoA thioesterases. The protein was identified by its biocapacity to increase mitochondrial steroidogenesis in a cell free bioassay. In the present study we measure the activity of ARTISt using arachidonoyl-CoA (AA-CoA) as substrate. We demonstrate that ACTH significantly stimulates endogenous mitochondrial thioesterase activity as early as 5 min after ACTH stimulation of Y1 cells. Nordihydroguaiaretic acid (NDGA), an inhibitor of AA release known to affect steroidogenesis, affects the in vitro activity of recombinant ARTISt and also the endogenous mitochondrial acyl-CoA thioesterases. ACTH activation of the enzyme protected ARTISt to the inhibitory effect of NDGA. These results show that an enzyme that release AA from AA-CoA can be regulated in intact cells by steroidogenic hormones.

Although the role of arachidonic acid (AA) in the regulation of steroidogenesis is well documented, the mechanism for AA release is not clear. Therefore, the aim of this study was to characterize the role of an acyl-CoA thioesterase (ARTISt) and an acyl-CoA synthetase as members of an alternative pathway in the regulation of the intracellular levels of AA in steroidogenesis. Purified recombinant ARTISt releases AA from arachidonoyl-CoA (AA-CoA) with a Km of 2 micro m. Antibodies raised against recombinant acyl-CoA thioesterase recognize the endogenous protein in both adrenal tissue and Y1 adrenal tumor cells by immunohistochemistry and immunocytochemistry and Western blot. Stimulation of Y1 cells with ACTH significantly stimulated endogenous mitochondrial thioesterases activity (1.8-fold). Nordihydroguaiaretic acid (NDGA), an inhibitor of AA release known to affect steroidogenesis, affects the in vitro activity of recombinant ARTISt and also the endogenous mitochondrial acyl-CoA thioesterases. ACTH-stimulated steroid synthesis in Y1 cells was significantly inhibited by a synergistic effect of NDGA and triacsin C an inhibitor of the AA-CoA synthetase. The apparent IC50 for NDGA was reduced from 50 micro m to 25, 7.5 and 4.5 micro m in the presence of 0.1, 0.5 and 2 micro m triacsin C, respectively. Our results strongly support the existence of a new pathway of AA release that operates in the regulation of steroid synthesis in adrenal cells.

Washbasins and metal drums are important sources of Aedes aegypti mosquitoes in much of Latin America. When manual cleaning was found to be ineffective in eliminating mosquito larvae in a community-based control programme in El Progreso, Honduras, it was decided to develop and evaluate an improved method of removing mosquito eggs based on commonly-available materials. The method, named La Untadita ('The Little Dab', in English), consists of five steps: mixing chlorine bleach and detergent to make a paste, applying the mixture to the walls of the container, waiting 10 min, scrubbing with a brush, and finally rinsing with water. A field trial of the Untadita was conducted in 13 peri-urban neighbourhoods. At the first post-intervention survey, in spite of high levels of exposure to the community-based intervention, high levels of knowledge regarding the Untadita and high levels of its reported use, little or no impact was discernable on mosquito larvae and pupae. The method was then modified by increasing the recommended quantities of bleach and detergent and simplifying the instructions. In the second post-intervention survey, knowledge of the steps and their order increased further; the intervention neighbourhoods had significantly fewer algae on washbasin walls, an indicator of more effective cleaning; and numbers of pupae and 3rd and 4th instar larvae were significantly lower than in untreated neighbourhoods. Effective promotion of the Untadita should be able to control mosquito infestation in many washbasins, especially those in frequent use, thus reducing the need for chemical and biological larvicides that may be either more costly or less acceptable to householders.

Householders in a community-based programme to control dengue in El Progreso, Honduras, are being encouraged to improve the cleaning of the water-storage containers in which many of the vectors thrive. The objective of the present study was to develop an indicator of the change occurring in human behaviour. Traditional Aedes aegypti larval indices do not differentiate between containers in which all the immature stages are present and those which hold only first- and second-instar larvae. However, it is not essential to prevent all larval development to limit transmission of pathogens by the adults; if the Ae. aegypti in the containers only manage to develop to young larvae before the containers are cleaned, then control of the vector in these containers will be effective. In field trials, sampling of third- and fourth-instar larvae in washbasins by taking five dips (quick immersions to a standard depth) with a hand-held net was found to be sufficient for estimating the true population size of that same cohort. This sampling method was then included in a large-scale survey of households, conducted for programme monitoring. An index was then developed as a summary measure of the degree of infestation of a washbasin by Ae. aegypti. This index was the sum of four variables assessed in the survey: presence of any immature stages (larvae and/or pupae); presence of pupae; detection of third-fourth-instar larvae in a five-dip sample; and a log-transformation of the number of larvae recovered. Based on this new index, the 884 washbasins encountered in the survey were classified as infestation-free (76.2%), or with low-(6.7%), medium-(14.9%) or high-level (2.2%) infestation. Application of the same procedure to 240 drums encountered in the survey showed that 66.3% were infestation-free and 9.2%, 17.1% and 7.4% had low-, medium- and high-level infestations, respectively. Compared with the traditional indices, this new index should be more sensitive to changes in human behaviour resulting from a control programme exposure than a simple, dichotomous variable (i.e. positive/negative for presence of immature stages). The use of such an index could make the control programme more efficient, allowing the greatest efforts to be targeted at households that have medium-high levels of infestation.

Chlorine bleach and detergent are routinely used by householders in El Progreso, Honduras in the process of cleaning washbasins and drums, the two most important larval habitats of Aedes aegypti in the city. The efficacy of these materials in eliminating eggs, larvae, and pupae of Ae. aegypti was assessed under controlled conditions. The promising results obtained led to trials using a combination of chlorine bleach and detergent to apply to the walls of washbasins and drums as a method for eliminating eggs. The bleach maintained its ovicidal properties when mixed with detergent, and the detergent gave the mixture consistency so that it could be applied as a thin film to the walls. This new procedure was named the little dab (Untadita in Spanish) and allows households to direct their efforts against a stage of the mosquito life cycle that has been ignored in the past: the egg.