Transgenic mice overexpressing CD109 in the epidermis display decreased inflammation and granulation tissue and improved collagen architecture during wound healing

Transforming growth factor‐β (TGF‐β) is a multifunctional growth factor involved in all aspects of wound healing. TGF‐β accelerates wound healing, but an excess of its presence at the wound site has been implicated in pathological scar formation. Our group has recently identified CD109, a glycophosphatidylinositol‐anchored protein, as a novel TGF‐β coreceptor and inhibitor of TGF‐β signaling in vitro. To determine the effects of CD109 in vivo on wound healing, we generated transgenic mice overexpressing CD109 in the epidermis. In excisional wounds, we show that CD109 transgenic mice display markedly reduced macrophage and neutrophil recruitment, granulation tissue area, and decreased Smad2 and Smad3 phosphorylation, whereas wound closure remains unaffected as compared with wild‐type littermates. Futhermore, we demonstrate that the expression of the proinflammatory cytokines interleukin‐1α and monocyte chemoattractant protein‐1, and extracellular matrix components is markedly decreased during wound healing in CD109 transgenic mice. In incisional wounds, CD109 transgenic mice show improved dermal architecture, whereas the tensile strength of the wound remains unchanged. Taken together, our findings demonstrate that CD109 overexpression in the epidermis reduces inflammation and granulation tissue area and improves collagen organization in vivo.     

Four-year follow-up of endoscopic gastroplication for the treatment of gastroesophageal reflux disease

AIM: To evaluate the long-term effect of Endocinch treatment for gastroesophageal reflux disease (GERD).METHODS: After unblinding and crossover, 50 patients (32 males, 18 females; mean age 46 years) with pH-proven chronic GERD were recruited from an initial randomized, placebo-controlled, single-center study, and included in the present prospective open-label follow-up study. Initially, three gastroplications using the Endocinch device were placed under deep sedation in a standardized manner. Optional retreatment was offered in the first year with 1 or 2 extra gastroplications. At baseline, 3 mo after (re) treatment and yearly proton pump inhibitor (PPI) use, GERD symptoms, quality of life (QoL) scores, adverse events and treatment failures (defined as: patients using > 50% of their baseline PPI dose or receiving alternative antireflux therapy) were assessed. Intention-to-treat analysis was performed.RESULTS: Median follow-up was 48 mo [interquartile range (IQR): 38-52]. Three patients were lost to follow-up. In 44% of patients retreatment was done after a median of 4 mo (IQR: 3-8). No serious adverse events occurred. At the end of follow-up, symptom scores and 4 out of 6 QoL subscales were improved (all P < 0.01 compared to baseline). However, 80% of patients required PPIs for their GERD symptoms. Ultimately, 64% of patients were classified as treatment failures. In 60% a post-procedural endoscopy was carried out, of which in 16% reflux esophagitis was diagnosed.CONCLUSION: In the 4-year follow-up period, the subset of GERD patients that benefit from endoscopic gastroplication kept declining gradually, nearly half opted for retreatment and 80% required PPIs eventually.     

Chapouthier,G. and Nouët,J.-C. (eds.): 1998, The Universal Declaration of Animal Rights. Comments and Intentions

Medicine, Health Care and Philosophy -     

Healing,Inflammation, and Fibrosis: Radiation-Induced Tissue Damage: Clinical Consequences and Current Treatment Options

Radiation therapy is a valuable tool in the treatment of numerous malignancies but, in certain cases, can also causes significant acute and chronic damage to noncancerous neighboring tissues. This review focuses on the pathophysiology of radiation-induced damage and the clinical implications it has for plastic surgeons across breast reconstruction, osteoradionecrosis, radiation-induced skin cancers, and wound healing. The current understanding of treatment modalities presented here include hyperbaric oxygen therapy, autologous fat grafting and stem cells, and pharmaceutical agents.     

Healing,Inflammation, and Fibrosis: Wound Healing: A Comprehensive Review

Wound healing is an intricate, tightly regulated process that is critical to maintaining the barrier function of skin along with preserving all other skin functions. This process can be influenced by a variety of modifiable and nonmodifiable factors. As wound healing takes place in all parts of the human body, this review focuses on cutaneous wound healing and highlights the classical wound healing phases. Alterations in any of these phases can promote chronic wound development and may impede wound healing.     

Healing,Inflammation, and Fibrosis: Comparison of Skin Substitutes for Acute and Chronic Wound Management

Chronic and acute wounds, such as diabetic foot ulcers and burns, respectively, can be difficult to treat, especially when autologous skin transplantations are unavailable. Skin substitutes can be used as a treatment alternative by providing the structural elements and growth factors necessary for reepithelialization and revascularization from a nonautologous source. As of 2020, there are 76 commercially available skin substitute products; this article provides a review of the relevant literature related to the major categories of skin substitutes available.     

Stable concentrations of zidovudine, stavudine, lamivudine, abacavir, and nevirapine in serum and cerebrospinal fluid during 2 years of therapy

For a number of antiretroviral drugs, prolonged suppression of viral replication is related to drug exposure. Therefore, it is important to maintain stable concentrations during prolonged therapy. While studies suggest that saquinavir concentrations decrease over time, we show that concentrations of zidovudine, stavudine, lamivudine, abacavir, and nevirapine in serum and cerebrospinal fluid are stable during 2 years of therapy.     

Leydig cell development in the pig testis during the late fetal and early postnatal period: An electron microscopic study with attention to the influence of fetal decapitation

The ultrastructure of fetal and postnatal pig Leydig cells was studied from 75 days postcoitum (p.c.) to 1 month after birth. Additionally, decapitated fetuses from 75 days p.c. until birth were used to study the effect of deprivation of gonadotrophins on the ultrastructure of Leydig cells. Normal Leydig cell development was characterized by a change in smooth endoplasmic reticulum (SER). Next to branched tubular SER, whirls of elaborate and tightly packed SER membranes appeared. The amount of SER increased with age but decreased slightly before the end of the observation period. Rough endoplasmic reticulum (RER) was a minor component. Large bundles or whirls of intermediate filaments were abundant until just before birth; thereafter, they decreased drastically. Peroxisome-like structures and crystalloid bodies were observed with increasing frequency from 75 days p.c. and 20 days postpartum onward. Polygonal lysosome-like dense bodies transformed into complex membranous structures especially after birth. Giant mitochondria occurred in the late fetal and postnatal period. From 75 days p.c. onward fully developed Leydig cells were scarce in testes of decapitated fetuses. Leydig cell characteristics disappeared toward the end of the fetal period; only the cell shape, the large bundles or whirls of intermediate filaments, some scarce polygonal lysosome-like dense bodies, and RER remained, but SER was negligible. Progressive hemorrhages apparent in situ were correlated positively with fetal age. The dependency of Leydig cells upon LH began between 60 and 75 days postcoitum.