Pentoxifylline inhibits the fibrogenic activity of pleural effusions and transforming growth factor-β

Physiopathology of organ fibrosis is far from being completely understood, and the efficacy of the available therapeutic strategies is disappointing. We chose pleural disease for further studies and addressed the questions of which cytokines are relevant in pleural fibrosis and which drugs might interrupt its development. We screened pleural effusions for mediators thought to interfere with fibrogenesis (transforming growth factor-β (TGF-β), tumour necrosis factor α (TNFα), soluble TNF-receptor p55 (sTNF-R)) and correlated the results with patient clinical outcome in terms of extent of pleural thickenings. We found pleural thickenings correlated with TGF-β (p < 0.005) whereas no correlations could be observed with TNFα and sTNF-R. Further, we were interested in finding out how TGF-β effects on fibroblast growth could be modulated. We found that pentoxifylline is able to inhibit both fibroblast proliferation and collagen synthesis independently of the stimulus. We conclude that, judging from in vitro studies, pentoxifylline might offer a new approach in the therapy of pleural as well as pulmonary fibrosis

Elevated urinary excretion of free pyridinoline in Friesian horses suggests a breed-specific increase in collagen degradation

Background: Friesian horses are known for their high inbreeding rate resulting in several genetic diseases such as hydrocephaly and dwarfism. This last decade, several studies focused on two other presumed hereditary traits in Friesian horses: megaoesophagus and aortic rupture. The pathogenesis of these diseases remains obscure but an important role of collagen has been hypothesized. The purpose of this study was to examine possible breed-related differences in collagen catabolism. Urinary specimens from Friesian (n = 17, median age 10 years old) and Warmblood horses (n = 17, median age 10 years old) were assessed for mature collagen cross-links, i.e. pyridinoline (PYD) (=hydroxylysylpyridinoline/HP) and deoxypyridinoline (DPD) (lysylpyridinoline /LP). Solid-phase extraction was performed, followed by reversed-phase ion-paired liquid chromatography prior to tandem mass spectrometry (MS/MS) detection. Results: Mean urinary concentrations of free PYD, expressed as fPYD/creatinine ratio, were significantly higher in Friesian horses compared to Warmblood horses (28.5 ± 5.2 versus 22.2 ± 9.6 nmol/mmol, p = 0.02) while mean fDPD/creatinine ratios were similar in both horse breeds (3.0 ± 0.7 versus 4.6 ± 3.7 nmol/mmol, p = 0.09). Conclusions: Since DPD is considered a specific bone degradation marker and PYD is more widely distributed in connective tissues, the significant elevation in the mean PYD/DPD ratio in Friesian versus Warmblood horses (9.6 ± 1.6 versus 5.7 ± 1.8, p < 0.0001) suggests a soft tissue origin for the increased fPYD levels. Considering that a previous study found no differences in total collagen content between Friesian and Warmblood horses for tendon and aortic tissue, this indicates a higher rate of collagen degradation. The latter might, at least in part, explain the predisposition of Friesians to connective tissue disorders

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P &lt; 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P &lt; 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Pentoxifylline inhibits the ® brogenic activity of pleural effusions and transforming growth factor-b

PHYSIOPATHOLOGY of organ brosis is far from being completely understood, and the ef cacy of the available therapeutic strategies is disappointing. We chose pleural disease for further studies and addressed the questions of which cytokines are relevant in pleural brosis and which drugs might interrupt its development. We screened pleural effusions for mediators thought to interfere with brogenesis (transforming growth factor-b (TGF-b), tumour necrosis factor a (TNFa), soluble TNF-receptor p55 (sTNF-R)) and correlated the results with patient clinical outcome in terms of ex tent of pleural thickenings. We found pleural thickenings correlated with TGF-b (P , 0 005) whereas no correlations could be observed with TNFa and sTNF-R. Further, we were interested in nding out how TGF-b effects on broblast growth could be modulated. We found that pentox ifylline is able to inhibit both broblast proliferation and collagen synthesis independently of the stimulus. We conclude that, judging from in vitro studies, pentox ifylline might offer a new approach in the therapy of pleural as well as pulmonary brosis

Amelogenesis imperfecta in a new animal model - a mutation in chromosome 5 (human 4q21).

Candidate genes for amelogenesis imperfecta (AI) and dentinogenesis imperfecta (DI) are located on 4q21 in humans. We tested our hypothesis that mutations in the portion of mouse chromosome 5 corresponding to human chromosome 4q21 would cause enamel and dentin abnormalities. Male C3H mice were injected with ethylnitrosourea (ENU). Within a dominant ENU mutagenesis screen, a mouse mutant was isolated with an abnormal tooth enamel (ATE) phenotype. The structure and ultrastructure of teeth were studied. The mutation was located on mouse chromosome 5 in an interval of 9 cM between markers D5Mit18 and D5Mit10. Homozygotic mutants showed total enamel aplasia with exposed dentinal tubules, while heterozygotic mutants showed a significant reduction in enamel width. Dentin of mutant mice showed a reduced content of mature collagen cross-links. We were able to demonstrate that a mutation on chromosome 5 corresponding to human chromosome 4q21 can cause amelogenesis imperfecta and changes in dentin composition

Marine Algae-PLA composites as de novo alternative to porcine derived collagen membranes

Resorbable and volume-stable collagen matrices have been preferred as grafting materials for diverse clinical applications in recent years. On the other hand, there is always an existing risk of transmission of infection with the cells or the tissues of the graft in using such collagen matrices. Moreover, considering the economic aspects, there is also a need for cost-efficient alternative materials. In this sense, marine algae can be considered as alternatives since they represent vast and cheap source of potential biopolymers. This work covers a comprehensive cytocompatibility study of composite biopolymers derived from different types of marine algae