Purpose
The surgical stress of total knee arthroplasty (TKA) procedure and the application of intra‐operative pneumatic thigh tourniquet increases local fibrinolytic activity, which contributes significantly to post‐operative blood loss. Tranexamic acid, an antifibrinolytic drug, is commonly used to control post‐operative blood loss. The recommended mode of administration of tranexamic acid is either oral or intravenous. However, the mechanism of action of the tranexamic acid points towards the possible effectiveness it may have following local/intra‐articular application. This prospective, double‐blinded, randomized preliminary study evaluated the efficacy of intra‐articular tranexamic acid in reducing TKA‐associated post‐operative blood loss.
Methods
Fifty consenting patients with osteoarthritis of the knee scheduled for primary unilateral cemented‐TKA were randomly allocated to one of the two groups: Tranexamic Acid (TA) group (n = 25, 500 mg/5 ml tranexamic acid) and the control group (n = 25, 5 ml 0.9% saline). The drug and control solution were administered intra‐articularly through the drain tube immediately after the wound closure. Parameters related to blood loss (drop in haemoglobin, haematocrit differential) and the drain output [volume (ml)] were compared between the two groups.
Results
On a comparative basis, TA‐group obtained significant reduction in the drain output [95% CI: 360.41–539.59, p < 0.001] at 48 h post‐operatively. Even though the control group received sixfold more blood transfusion than TA‐group, it showed a greater drop in haemoglobin and haematocrit (p < 0.05).
Conclusions
Local application of tranexamic acid seems to be effective in reducing post‐TKA blood loss as well as blood transfusion requirements.
Level of evidence
Therapeutic study, Level II.
The NKX3.1 homeobox gene plays essential roles in prostate differentiation and prostate cancer. We now show that loss-of-function of Nkx3.1 in mouse prostate results in down-regulation of genes that are essential for prostate differentiation, as well as up-regulation of genes that are not normally expressed in prostate. Conversely, gain-of-function of Nkx3.1 in an otherwise fully-differentiated non-prostatic mouse epithelium is sufficient for re-specification to prostate in renal grafts in vivo. In human prostate cells, these activities require the interaction of NKX3.1 with the G9a histone methyltransferase via the homeodomain, and are mediated by activation of target genes such as UTY (KDM6c), the male-specific paralog of UTX (KDM6a). We propose that an NKX3.1-G9a-UTY transcriptional regulatory network is essential for prostate differentiation, and we speculate that disruption of such network predisposes to prostate cancer.
Histone methylation is known to dynamically regulate diverse developmental and physiological processes. Histone methyl marks are written by methyltransferases and erased by demethylases, and result in modification of chromatin structure to repress or activate transcription. However, little is known about how histone methylation may regulate defense mechanisms and flowering time in plants. Here we report characterization of JmjC DOMAIN-CONTAINING PROTEIN 27 (JMJ27), an Arabidopsis JHDM2 (JmjC domain-containing histone demethylase 2) family protein, which modulates defense against pathogens and flowering time. JMJ27 is a nuclear protein containing a zinc-finger motif and a catalytic JmjC domain with conserved Fe(II) and α-ketoglutarate binding sites, and displays H3K9me1/2 demethylase activity both in vitro and in vivo. JMJ27 is induced in response to virulent Pseudomonas syringae pathogens and is required for resistance against these pathogens. JMJ27 is a negative modulator of WRKY25 (a repressor of defense) and a positive modulator of several pathogenesis-related (PR) proteins. Additionally, loss of JMJ27 function leads to early flowering. JMJ27 negatively modulates the major flowering regulator CONSTANS (CO) and positively modulates FLOWERING LOCUS C (FLC). Taken together, our results indicate that JMJ27 functions as a histone demethylase to modulate both physiological (defense) and developmental (flowering time) processes in Arabidopsis.
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