Level of estrogen receptors (ER) as a function of histological malignancy stages of tumors in patients with breast neoplasm]

The presence of estrogen receptors (ER) has been studied in 70 patients with primary operable breast cancer. The tumors were graded histologically according to Bloom and Richardson criteria. A significant correlation was found between these two prognostic factors: the better--differentiated tumors (I + II histological grade) had significantly higher level of ER than that in the poor--differentiated tumors. Estrogen receptor content of primary breast cancer as a function of tumor grade can be useful in selection of the most efficient treatment modalities for individual patients.     

Biofilms grown in aquatic microcosms affect mercury and selenium accumulation in Daphnia

Experiments examining mercury (Hg) toxicity in Daphnia are usually conducted in highly standardized conditions that prevent the formation of biofilm. Although such standardization has many advantages, extrapolation of results to natural conditions and inference of ecological effects is challenging. This is especially true since biofilms can accumulate metals/metalloids and play a key role in their transfer to higher trophic level organisms. In this study, we experimentally tested the effects of spontaneously appearing biofilm in Daphnia cultures on accumulation of Hg and its natural antagonist selenium (Se) in Daphnia magna. We added Hg (in the form of mercury (II) chloride) at two concentrations (0.2 µg/L and 2 µg/L) to experimental microcosms and measured the uptake of Hg and Se by D. magna in the presence and absence of biofilm. To test for consistent and replicable results, we ran two identical experimental sets one week apart. Biofilm presence significantly reduced the accumulation of Hg, while increasing the tissue Se content in D. magna, and these findings were reproducible across experimental sets. These findings indicate that highly standardized tests may not be adequate to predict the bioaccumulation and potential toxicity of metals/metalloids under natural conditions.     

Nail changes in chronic renal failure patients under haemodialysis

Background Chronic renal failure is known to cause various nail pathologies. They may be directly related to the renal condition itself or its complications or to the therapy. Objective To compare nail changes in end‐stage renal failure patients under haemodialysis with healthy persons and to study the potential relationship with various parameters in the patients. Patients and Methods The study comprised 100 patients with chronic renal failure under regular haemodialysis as well as 100 healthy control subjects of matched age and sex. Both groups were subjected to full history taking and thorough general and nail examination. Complete blood picture, liver and kidney function tests and fasting blood glucose level were investigated. Results Nail disorders were more prevalent in patients (76%) than in control group (30%). The half and half nail was the most common finding (20%) followed by – in descending manner – absent lunula, onycholysis, brittle nail, Beau's lines, clubbing, longitudinal ridging, onychomycosis, subungual hyperkeratosis, koilonychias, total leukonychia, splinter hemorrhage, pitting and pincer nail deformity. There was non‐significant correlation between nail changes and age of the patients or duration of haemodialysis. In addition, no evidence of significant relation was found between nail changes and both haemoglobin and albumin levels. Conclusion Frequent nail changes are observed on systematic nail examination of uraemic patients undergoing haemodialysis; however, the cause of them remains obscure and could not be traced to a particular abnormality in the renal condition, medication or the procedure itself and it needs further investigations.     

Ciliary IFT88 Protects Coordinated Adolescent Growth Plate Ossification From Disruptive Physiological Mechanical Forces

Compared with our understanding of endochondral ossification, much less is known about the coordinated arrest of growth defined by the narrowing and fusion of the cartilaginous growth plate. Throughout the musculoskeletal system, appropriate cell and tissue responses to mechanical force delineate morphogenesis and ensure lifelong health. It remains unclear how mechanical cues are integrated into many biological programs, including those coordinating the ossification of the adolescent growth plate at the cessation of growth. Primary cilia are microtubule-based organelles tuning a range of cell activities, including signaling cascades activated or modulated by extracellular biophysical cues. Cilia have been proposed to directly facilitate cell mechanotransduction. To explore the influence of primary cilia in the mouse adolescent limb, we conditionally targeted the ciliary gene Intraflagellar transport protein 88 (Ift88^fl/fl) in the juvenile and adolescent skeleton using a cartilage-specific, inducible Cre (AggrecanCreER^T2 Ift88^fl/fl). Deletion of IFT88 in cartilage, which reduced ciliation in the growth plate, disrupted chondrocyte differentiation, cartilage resorption, and mineralization. These effects were largely restricted to peripheral tibial regions beneath the load-bearing compartments of the knee. These regions were typified by an enlarged population of hypertrophic chondrocytes. Although normal patterns of hedgehog signaling were maintained, targeting IFT88 inhibited hypertrophic chondrocyte VEGF expression and downstream vascular recruitment, osteoclastic activity, and the replacement of cartilage with bone. In control mice, increases to physiological loading also impair ossification in the peripheral growth plate, mimicking the effects of IFT88 deletion. Limb immobilization inhibited changes to VEGF expression and epiphyseal morphology in Ift88cKO mice, indicating the effects of depletion of IFT88 in the adolescent growth plate are mechano-dependent. We propose that during this pivotal phase in adolescent skeletal maturation, ciliary IFT88 protects uniform, coordinated ossification of the growth plate from an otherwise disruptive heterogeneity of physiological mechanical forces. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Efficacy of short‐course lansoprazole with clarithromycin and amoxicillin in the eradication of Helicobacter pylori in South‐East Asian patients: 5‐day t.d.s. versus 7‐day b.d. treatment regimens

OBJECTIVE : To determine and compare the efficacy of 5‐day t.d.s and 7‐day b.d. treatment regimens comprising lansoprazole, clarithromycin and amoxicillin in the eradication of Helicobacter pylori. METHODS : Patients with unequivocal evidence of H. pylori infection based on histology and rapid urease tests of both antrum and corpus biopsies were recruited for the study. The study was a randomized, investigator‐blind, comparative study. Patients received either 500 mg clarithromycin t.d.s. and 500 mg amoxicillin t.d.s. for 5 days (LAC5) or 500 mg clarithromycin b.d. and 500 mg amoxicillin b.d. for 7 days (LAC7) together with 30 mg lansoprazole (both groups) daily for either 5 or 7 days, depending on the treatment group. Patients were assessed for the successful eradication of H. pylori, defined as the absence of bacteria based on histology and urease tests on both antral and corporeal biopsies, carried out at least 4 weeks after completion of the therapy. RESULTS : One hundred and eight patients were recruited for the study. In the LAC5 treatment group, four patients failed to return for follow up and in the LAC7 group, two failed to return for follow up and two were not compliant with medications. Eradication rates based on an intention‐to‐treat analysis were: 46/54 for LAC5 (85.2%; 95% CI = 72.9–93.4) and 47/54 for LAC7 (87.0%; 95% CI = 75.1–94.6). Based on a per protocol analysis, the rates were: 46/50 for LAC5 (92.0%; 95% CI = 80.8–97.8) and 47/50 for LAC7 (94.0%; 95% CI = 83.5–98.7). Both treatment regimens were convenient for patients and except for two patients in the LAC7 group, all patients reported taking 100% of all prescribed medications. The side‐effects encountered were uniformly mild and no patient discontinued treatment because of intolerance to medications. The most common side‐effects were altered taste (LAC5 64.7%; LAC7 78.8%). Diarrhea, nausea and anorexia were reported in a minority of patients. CONCLUSIONS : Both the LAC5 t.d.s. and the LAC7 b.d. treatment regimens were well tolerated by patients and were highly effective in the eradication of H. pylori.     

Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitis

INTRODUCTION: Interleukin 10 knockout (IL-10-/-) mice spontaneously develop a Th1 T cell mediated colitis with many similarities to Crohn's disease. Daily injections of IL-10 are unable to induce remission in mice with established disease. In contrast, we have shown previously that intravenous administration of adenoviral vectors encoding IL-10 (AdvmuIL-10) induces hepatic IL-10 release and leads to long term disease suppression with profound systemic immunoregulatory changes. AIMS: To determine whether rectal delivery of AdvmuIL-10 induces localised colonic IL-10 expression without systemic immune suppression, and assess its therapeutic efficacy in IL-10-/- mice with established colitis. RESULTS: A single rectal infusion of 5 x 10(8) PFU AdvmuIL-10 to 10 week IL- 10-/- mice resulted in a median level of 27.3 pg/mg IL-10 in colonic homogenates harvested one week later. IL-10-/- mice with established colitis treated with an enema of 5 x 10(8) PFU AdvmuIL-10 entered clinical and histological remission whereas empty cassette adenovirus (Adv0) or phosphate buffered saline (PBS) treated mice developed progressive disease. After four weeks, the histological score of AdvmuIL-10 treated mice (4.4 (1.5)) was significantly lower than that of Adv0 (11.1 (1.1); p<0.001) and PBS (10.9 (1.0); p<0.01) treated controls. In addition, the stool concentration of IL-1beta over the four week experiment was significantly higher in mice treated with saline or Adv0 than in those treated with AdvmuIL-10 (p<0.01). CONCLUSION: Local AdvmuIL-10 therapy reverses colitis in IL-10-/- mice without the systemic effects seen after intravenous administration. Gene therapy strategies using adenoviral vectors encoding immunoregulatory cytokines may prove to be a potent approach to the treatment of chronic inflammatory diseases such as Crohn's disease.