Load-induced proteoglycan orientation in bone tissuein vivo andin vitro

Summary Previous studies of Alcian blue-induced birefringence in adult avian cortical bone showed that a short period of intermittent loading rapidly produces an increased level of orientation of proteoglycans within the bone tissue. In the absence of further loading, this persists for over 24 hours. We have proposed that this phenomenon could provide a means for “capturing” the effects of transient strains, and so provide a persistent, constantly updated strain-related influence on osteocyte populations related to the bones' averaged recent strain history, in effect, a “strain memory” in bone tissue. In our present study, we use the Alcian blue-induced birefringence technique to demonstrate that proteoglycan orientation also occurs after intermittent loading of both cortical and cancellous mammalian bonein vivo andin vitro. We also show that the change in birefringence is proportional to the magnitude of the applied strain, and that the reorientation occurs rapidly, reaching a maximal value after only 50 loading cycles. Examination of electron micrographs of bone tissue after staining with cupromeronic blue allows direct visualization and quantification of the change in proteoglycan orientation produced by loading. This shows that intermittent loading is associated with a realignment of the proteoglycan protein cores, bringing them some 5 degrees closer to the direction of collagen fibrils in the bone matrix.     

Indole-3-carbinol and 3,3'-diindolylmethane induce apoptosis in human prostate cancer cells.

Cruciferous vegetables contain glucobrassicin which, during metabolism, yields indole-3-carbinol (I3C). In a low pH environment I3C is converted into polymeric products, among which 3,3'-diindolylmethane (DIM) is the main one. The apoptotic effects of I3C and DIM were exhibited in human breast cancer cells. The objectives of this study were: (a) examination of the potential effects of I3C and DIM on the proliferation and induction of apoptosis in human prostate cancer cell lines with different p53 status; (b) to try to characterise the mechanism(s) involved in these effects. Our results indicate that both indole derivatives suppress the growth of these cells in a dose- and time-dependent manner, by inducing apoptosis. It appears that these indolic compounds may offer effective means against prostate cancer. Induction of apoptosis was p53-independent. Moreover, the indole derivatives employed did not affect the levels of bcl-2, bax and fasL.     

Mechanotransduction of bone cells<Emphasis Type="Italic">in vitro</Emphasis>: Mechanobiology of bone tissue

Mechanical force plays an important role in the regulation of bone remodelling in intact bone and bone repair. In vitro, bone cells demonstrate a high responsiveness to mechanical stimuli. Much debate exists regarding the critical components in the load profile and whether different components, such as fluid shear, tension or compression, can influence cells in differing ways. During dynamic loading of intact bone, fluid is pressed through the osteocyte canaliculi, and it has been demonstrated that fluid shear stress stimulates osteocytes to produce signalling molecules. It is less clear how mechanical loads act on mature osteoblasts present on the surface of cancellous or trabecular bone. Although tissue strain and fluid shear stress both cause cell deformation, these stimuli could excite different signalling pathways. This is confirmed by our experimental findings, in human bone cells, that strain applied through the substrate and fluid flow stimulate the release of signalling molecules to varying extents. Nitric oxide and prostaglandin E₂ values increased by between two- and nine-fold after treatment with pulsating fluid flow (0.6±0.3 Pa). Cyclic strain (1000 μstrain) stimulated the release of nitric oxide two-fold, but had no effect on prostaglandin E₂. Furthermore, substrate strains enhanced the bone matrix protein collagen I two-fold, whereas fluid shear caused a 50% reduction in collagen I. The relevance of these variations is discussed in relation to bone growth and remodelling. In applications such as tissue engineering, both stimuli offer possibilities for enhancing bone cell growth in vitro.     

Retarded myelination in the lumbar spinal cord of piglets born with spread-leg syndrome

Piglets born with spread-leg syndrome, a congenital weakness of the hindlimb adductors, were investigated to determine the site of lesion leading to limb impairment. Histological and immunohistochemical studies of the motor neuron unit showed no alterations but quantitative analysis revealed a reduction of axonal diameter and myelin sheath-thickness of the fibres innervating the adductors of the affected limbs. In the lumbar spinal cord a lack of myelination was observed in the tracts descending to the lower motor neurons. Recovery from the syndrome was accompanied by a catching-up of myelination with that of the controls. The spread-leg syndrome is due to a nutritional deficiency in the sow; thus it is assumed that the deficient maternal substances, mainly choline and methionine, are essential for the normal myelin production by spinal white matter oligodendrocytes of the fetus.     

Abortive potency of Chlamydophila abortus in pregnant mice is not directly correlated with placental and fetal colonization levels

Abortion, placental and fetal colonization, and levels of gamma interferon were analyzed for four Chlamydophila abortus strains presenting antigenic variations in a mouse model. Expression of virulence of these strains varied and indicated that abortion was not directly related to the number of bacteria in the placenta, and thus, other factors may have an important role in activating the abortion process.     

Antimicrobial susceptibility and frequency of occurrence of clinical blood isolates in Sfax-Tunisia (1993-1998)

Antimicrobial susceptibility and frequency of occurrence of clinical blood isolates in Sfax-Tunisia (1993-1998). The choice of antimicrobial therapy for the treatment of bacteremia is often empirical and based on the knowledge of susceptibility profiles of the most common bacteria causing such infections. This study determines the bacterial etiology of bacteremic episodes and antimicrobial susceptibility patterns recorded at a teaching hospital, from January 1993 to December 1998. We collected 2979 strains responsible for bacteremia. Gram negative bacteria were predominant (60%). The organisms recovered most frequently were Staphylococcus aureus (18.9%), Escherichia coli (14.7%), Klebsiella pneumoniae (14%) and Pseudomonas aeruginosa (7.6%). The incidence of resistance to methicillin were 17.4% for Staphylococcus aureus and 26.8% for coagulase negative Staphylococcus. No resistance to glycopeptides was observed among the enterococci and staphylococci studied. 27.7% of enterobacteriaceae were resistant to third generation cephalosporins. Imipenem was the most active agent against gram negative bacteria. To carry out a surveillance of bacteremic episodes occurring at every hospital, it is necessary to provide valuable information which should be the basis for effective empiric therapy.     

Takayasu’s arteritis occurring under TNF blockers in a patient with spondyloarthritis: is it an association or a paradoxical effect?

Coexistence of spondyloarthritis (SpA) and Takayasu’s arteritis is not a common finding, but such cases have been discussed, particularly in the context of choice of therapy. Inhibition of inflammation by tumor necrosis factor inhibitors (TNFi) is a key aspect of the treatment of SpA and also positive effects of such treatment in concomitant large vessel vasculitis have been reported. However, TNFi is also associated with the possibility of initiating vasculitis.The present article based on a case study and the available literature is an attempt to discuss coexistence of these two diseases and the impact of treatment with biological drugs from the anti-TNF group in the course of SpA with Takayasu’s arteritis.     

Combined effect of Controlling Nutritional Status and Acute Kidney Injury on severe COVID-19 short-term outcomes

Introduction/ObjectivesAcute kidney injury (AKI) and malnutrition are two complications commonly reported in severe forms of COVID-19, their combined effect on short-term mortality is, however, not yet investigated. The objective of this study is to determine both their individual and combined effects on short-term prognosis.Materials and methodsThis is a prospective, uni-centric study, including 247 severe COVID-19 patients, admitted between April 25th and June 20th, 2020, at the University Hospital of Blida. AKI was defined according to the KDIGO-2012 guidelines. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score. The association with in-hospital mortality was assessed using the Kaplan-Meier method and proportional Cox regression.ResultsAmong the 247 severely affected COVID-19 patients included in this study, 34.4% developed AKI, 30.4 and 1.2%, respectively, had moderate and severe CONUT scores, 17.7% worsened and progressed to a critical state and 26.7% did not survive. Both AKI and CONUT score were significantly associated with mortality in a dose-response manner (pLog-Rank < 0.0001). Their relative risks are respectively (HR = 3.25 CI 95% [1.99–5.3] and HR = 2.42 CI 95% [1.5–3.9], p < 0.0001). In multivariate analysis, the highest risk was observed for the AKI-CONUT-high combination (HR = 3.0, 95% CI [1.5–6.1], p = 0.002).ConclusionA possible synergistic interaction between AKI and CONUT score for COVID-19 short-term mortality has been highlighted. Monitoring of renal function associated with assessment of nutritional status should be performed routinely and systematically from the early stages of admission.