An engineered biopolymer prevents mucositis induced by 5-fluorouracil in hamsters

Oral mucositis is a common, treatment-limiting, and costly side effect of cancer treatments whose biological underpinnings remain poorly understood. In this study, mucositis induced in hamsters by 5-fluorouracil (5-FU) was observed after cheek-pouch scarifications, with and without administration of RGTA (RG1503), a polymer engineered to mimic the protective effects of heparan sulfate. RG1503 had no effects on 5-FU-induced decreases in body weight, blood cell counts, or cheek-pouch and jejunum epithelium proliferation rates, suggesting absence of interference with the cytotoxic effects of 5-FU. Extensive mucositis occurred in all of the untreated animals, and consisted of severe damage to cheek pouch tissues (epithelium, underlying connective tissue, and muscle bundles). Only half of the RG1503-treated animals had mucositis, over a mean area 70% smaller than in the untreated animals. Basement membranes were almost completely destroyed in the untreated group but was preserved in the RG1503 group. RG1503 blunted or abolished the following 5-FU-induced effects: increases in matrix metalloproteinase (MMP)-2, MMP-9, and plasmin, and decreases in tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These data indicate that mucositis lesions are related to massive release of proteolytic enzymes and are improved by RG1503 treatment, this effect being ascribable in part to restoration of the MMP-TIMP balance. RG1503 given with cancer treatment might protect patients from mucositis.     

Mast cells accumulate in rat bone marrow after ovariectomy

We have previously shown that mast cells (MC) may act as accessory cells of bone resorption in a synchronized model of resorption. The aim of this study was to verify whether bone marrow MC accumulated during the phase of rapid osteopenia development in estrogen-deprived rats. Sprague-Dawley rats, 90 days old, were subjected to bilateral ovariectomy (OVX) or sham surgery (controls). Bone histomorphometry was performed in the proximal tibia metaphysis. Thirty days after surgery, serum estradiol had dropped (p < 0.002), and osteopenia was well established in the OVX rats (trabecular bone volume decreased by 69%, p < 0.0001). The indices of bone resorption were strongly modified: the number (p < 0.0001) and individual activity (p < 0.001) of the trabecular osteoclasts were prominently increased in the OVX rats. Ovariectomy resulted in a dramatic increase in the number of bone marrow MC (p < 0.0001), 97% of which were of the mucosal subtype. These results show that MC accumulate concomitantly with osteoclast generation in estrogen-deficient rats. Although the biological significance of this MC increase is unknown from these results, we hypothesize that MC might play a role in ovariectomy-induced bone loss similar to that they we previously proposed in a mechanically activated model of resorption.     

Bandnaht und/oder Kapsulodese bei skapholunärer Instabilität

We have reviewed 37 patients with scapholunate instability, operated in Paris between 1979 and 1995 7 months after the injury. There were 12 partial and 18 complete ligament ruptures, but also 4 distensions. The repair was a secondary suture in 16 cases (7 direct, 1 transosseous, 1 combined, 5 anchor, 2 transosseous with anchor). A capsulodesis was performed 7 times as an isolated and 8 times as a combined procedure. 6 previous cases have been treated by ligamentoplasty. We present the results after a mean postoperative follow-up of 27 months, with good results on pain and grip, maintaining a satisfactory range of motion.     

COVID‐19 in a high‐risk dual heart and kidney transplant recipient

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is rapidly infecting people worldwide, resulting in the infectious disease coronavirus disease 19 (COVID‐19) that has been declared a pandemic. Much remains unknown about COVID‐19, including its effects on solid organ transplant (SOT) recipients. Given their immunosuppressed state, SOT recipients are presumed to be at high risk of complications with viral infections such as SARS‐CoV‐2. Limited case reports in single SOT recipients, however, have not suggested a particularly severe course in this population. In this report, we present a dual‐organ (heart/kidney) transplant recipient who was found to have COVID‐19 and, despite the presence of a number of risk factors for poor outcomes, had a relatively mild clinical course.     

Enhancement of phagocytic activity of human monocytic-macrophagic cells by immunostimulating peptides from human casein

Two immunostimulating peptides, Val-Glu-Pro-Ile-Pro-Tyr and Gly-Leu-Phe, obtained from human caseins, were demonstrated to significantly stimulate binding of human senescent red blood cells to human monocytic-macrophagic cells and their phagocytosis by these cells.     

Changes in mast cell number during the activation phase of an induced synchronized remodeling sequence in the rat

Increase in mast cell (MC) number has been reported in some pathological conditions with increased remodeling. However, it is not known whether MCs are involved in the physiological remodeling of bone. In the present study the possible variations in MCs were investigated during the activation phase in a rat model of synchronized remodeling. Seven groups of 10 rats were used. As early as the first day of induction, MCs increased by 50% and then decreased on day 2. The same pattern of changes recurred on days 3 and 4. Intact non-degranulating MCs increased mainly at some distance from the bone surface. Degranulating MCs conversely decreased near the cambium layer of the periosteum. Prostaglandins were not involved in these changes. These results suggest an association between the events leading to the onset of bone resorption and MCs. Degranulation might induce the release of agents active on these events.     

IRF6 gene variants in Central European patients with non‐syndromic cleft lip with or without cleft palate

Variants in the interferon regulatory factor 6 (IRF6) gene have repeatedly been associated with non‐syndromic cleft lip with or without cleft palate (NSCL/P). A recent study has suggested that the functionally relevant variant rs642961 is the underlying cause of the observed associations. We genotyped rs642961 in our Central European case–control sample of 460 NSCL/P patients and 952 controls. In order to investigate whether other IRF6 variants contribute independently to the etiology of NSCL/P, we also genotyped the non‐synonymous coding variant V274I (rs2235371) and five IRF6‐haplotype tagging single nucleotide polymorphisms (SNPs). A highly significant result was observed for rs642961 (P = 1.44 × 10^?6) in our sample. The odds ratio was 1.75 [95% confidence interval (CI): 1.38–2.22] for the heterozygous genotype and 1.94 (95% CI: 1.21–3.10) for the homozygous genotype, values that are similar to those reported in a previously published family‐based study. Our results thus confirm the involvement of the IRF6 variant, rs642961, in the etiology of NSCL/P in the Central European population. We also found evidence suggestive of an independent protective effect of the coding variant V274I. In order to understand fully the genetic architecture of the IRF6 locus, it will be necessary to conduct additional SNP‐based and resequencing studies using large samples of patients.     

Histopathologic comparison of normal and hyperplastic condyles

OBJECTIVE: The aim of this study was to compare normal and hyperplastic mandibular condyles using two different histopathologic staining techniques. STUDY DESIGN: Nine cases of condylar hyperplasia and 13 normal cases were studied after hematoxylin and eosin and silver staining. RESULTS: There was a significant difference between the two groups in the thickness of the hyperplastic cartilage layer of condylar soft tissue (P = 0.017). Also, the number of argyrophilic nucleolar organizer regions was significantly higher in the condylar hyperplasia case group (P = 0.0001). No significant differences could be demonstrated in cartilage island frequency, penetration depth, and distribution in the cancellous bone of condyles. CONCLUSION: The thickness of the hyperplastic cartilage layer appears significantly increased in condylar hyperplasia. In addition, argyrophilic nucleolar organizer region count may be useful in histopathological identification of condylar hyperplasia.