Outcome of transcanalicular laser dacryocystorhinostomy with endonasal augmentation in acute versus post-acute dacryocystitis.

OBJECTIVE: To study the outcomes of transcanalicular laser dacryocystorhinostomy (TCL-DCR) with endonasal augmentation in acute versus post-acute dacryocystitis and compare it with external DCR in post-acute settings. METHODS: A prospective, randomised study was conducted in 90 adult cases of Acute dacryocystitis. All the patients were started on systemic antibiotics and a 4 mm × 4 mm osteotomy was created using TCL-DCR. The osteotomy was enlarged to 8 mm × 8 mm by endonasal augmentation at the same sitting in group 1, after 10 days in group 2 and after 10 days with external DCR in group 3. The cases were assessed for symptomatic relief and complications. Success was defined as functional and anatomical patency at 36 months. RESULTS: The mean age was 45.33 ± 15.06 years and the male: female ratio was 1:2. The presenting complaints were painful swelling (100%), epiphora or discharge (88.8%), fistula (33%) and fever (6%). The average number of acute episodes was 2.96. The intra-group pain reduction from day 1 to day 4, was significant in all three groups (p = 0.000). Intra-operative (p = 0.015, χ2 = 8.37) and post-operative complications (p = 0.002, χ2 = 0.002) were higher in group. Anatomical success was achieved in all the three groups, however, the functional success in Group 3, Group 2 and Group 1 was 100%, 86.7% and 66.7% respectively (p = 0.002, χ2 = 12.86). CONCLUSIONS: The creation of osteotomy using TCL-DCR provides early relief in symptoms. Single-stage surgery in inflamed tissues is associated with higher complication rates. External DCR in post-acute settings gives the best outcomes with minimal complications, endoscopic augmentation requires a close follow-up.

Sepsis downregulates aortic Notch signaling to produce vascular hyporeactivity in mice.

Inhibition of Notch signaling in macrophages is known to reduce inflammation, however, its role in regulating vascular hyporeactivity in sepsis is unknown. Thus we aimed to evaluate the effect of sepsis on vascular Notch signaling. Polymicrobial sepsis was induced by caecal ligation and puncture (CLP) in mice. mRNA expressions of Notch receptors (Notch1,3) and ligands (Jag1, Dll4), and downstream effector genes (Hey1, MLCK, MYPT1) were assessed by RT-qPCR. Protein level of activated Notch (NICD) was assessed by Western blot and immuno-histochemistry. Isometric tension in isolated aortic rings was measured by wire myography.CLP down-regulated aortic expression of Notch3, Jag1 and Dll4 as compared to control mice. Additionally, the protein level of NICD was found to be lesser in aortic tissue sections from CLP mice. Expression of Hey1 and MLCK were attenuated whereas MYPT1 expression was increased in septic mouse aorta. DAPT pretreatment did not improve CLP-induced vascular hyporeactivity to NA, CaCl2 and high K+ (80 mM), rather significantly attenuated the aortic response to these vasoconstrictors in control mice. Treatment with 1400 W reversed attenuated Notch3 (but not Jag1 and MLCK) expression in septic mouse aorta. In conclusion, sepsis significantly attenuated the Notch (especially Notch3) signaling in mouse aorta along with reduction in contractile gene expression and vasoconstriction response. Further, iNOS/NO pathway was involved in sepsis-induced down-regulation of Notch3 receptor. Thus systemic inhibition of Notch signaling during sepsis may have serious impact on sepsis-induced vascular hyporeactivity.

Calcium signaling cascades differentially regulate PGF2α-induced myometrial contractions in water buffaloes (Bubalus bubalis).

This study unravels the differential involvement of calcium signaling pathway(s) in PGF2α-induced contractions in myometrium of nonpregnant (NP) and pregnant buffaloes. Compared to the myometrium of pregnant animals, myometrium of NP buffaloes was more sensitive to PGF2α as manifested by changes in mean integral tension (MIT) and tonicity. In the presence of nifedipine, myometrial contraction to PGF2α was significantly attenuated in both NP and pregnant uteri; however, mibefradil and NNC 55-0396 produced inhibitory effects only in uterus of pregnant animals, thus suggesting the role of extracellular Ca2+ influx through nifedipine-sensitive L-type Ca2+-channels both in NP and pregnant, but T-type Ca2+ channels seem to play a role only during pregnancy. Entry of extracellular Ca2+ is triggered by enhanced functional involvement of Pyr3-sensitive TRPC3 channels and Rho-kinase pathways as evidenced by a significant rightward shift of the concentration-response curve of PGF2α in the presence of Pyr3 and Y-27632 in NP myometrium. But significant down-expressions of TRPC3 and Rho-A proteins during pregnancy apparently facilitate uterine quiescence. In the presence of Ca2+-free solution and cyclopiazonic acid (SERCA blocker), feeble contraction to PGF2α was observed in both NP and pregnant myometrium which suggests minor role of intracellular source of Ca2+ in mediating PGF2α-induced contractions in these tissues.