BIOLOGICAL SIGNIFICANCE: The Javan spitting cobra, Naja sputatrix is by itself a unique species and should not be confused as the equatorial and the Indochinese spitting cobras. The distinction among the spitting cobras was however unclear prior to the revision of cobra systematics in the mid-90's, and results of some earlier studies are now questionable as to which species was implicated back then. The current study successfully profiled the venom proteome of authenticated N. sputatrix, and showed that the venom is made up of approximately 64% three-finger toxins (including neurotoxins and cytotoxins) and 31% phospholipases A2 by total venom proteins. The findings verified that the paralyzing components in the venom i.e. neurotoxins are predominantly the short-chain subtype (SNTX) far exceeding the long-chain subtype (LNTX) which is more abundant in the venoms of monocled cobra and Indian common cobra. The neurotoxicity of N. sputatrix venom is hence almost exclusively SNTX-driven, and effective neutralization of the SNTX is the key to early reversal of paralysis. Unfortunately, as shown through a toxin-specific assay, the immunological neutralization of the SNTX using the Indonesian antivenom (SABU) was extremely weak, implying that SABU has limited therapeutic efficacy in treating N. sputatrix envenomation clinically. From the practical standpoint, actions need to be taken at all levels from laboratory to production and policy making to ensure that the shortcoming is overcome.
METHODS: Eight nulliparous women diagnosed with POP ≥ stage 3 between January 2005 and August 2013, according to the Pelvic Organ Quantification System (POPQ), were reviewed. Seven were managed surgically and one was managed with pessary. Primary outcome was surgical objective cure (POP-Q ≤ 1) and subjective cure, defined as negative response to questions 2 and 3 on Pelvic Organ Prolapse Distress Inventory 6. Secondary outcomes were complications, symptoms' severity and quality of life according to validated questionnaires.
RESULTS: A total of 1275 prolapse patients with POP-Q ≥ stage 3 were managed surgically, among whom seven (0.55%) were nulliparous. Each woman had at least one risk factor associated with POP. Risk factors identified were history of pelvic trauma, obesity, menopause, chronic cough, hard physical labor and constipation. Five patients underwent surgical correction (vaginal hysterectomy with sacrospinous fixation) with mesh (Perigee, n = 3; Avaulta, n = 2). Two patients had uterine preservation without mesh (hysteropexy with sacrospinous ligament fixation). One patient preferred treatment with pessary. The total cure rate (objective and subjective cure rates) was 86% after surgical reconstructive surgery.
CONCLUSION: Management of nulliparous advanced POP poses significant challenges with regard to uterine preservation, future pregnancy and childbirth. Conservative management with pessary insertion should be offered followed by surgical correction. Reconstructive surgery with mesh may improve prolapse symptoms objectively and subjectively.
METHODS: Cell proliferation, migration, TUNEL assay, western blotting, time-lapse confocal microscopy analyses, chorioallantoic membrane assay, and a xenograft BALB/c nude mouse system were used in this study. Chemical fingerprinting of AC-3E was established using LC-MS.
RESULTS: AC-3E attenuated T47D breast cancer cell activity by deregulating the PI3K/Akt/mTOR signaling pathway and key cell-cycle mediators, and inducing apoptosis. AC-3E also effectively inhibited tube-like structures of endothelial cells, blood vessel branching and microvessel formation ex vivo and in vivo. Significant preventive and therapeutic effects against T47D mammary tumor growth of AC-3E was observed comparable or superior to tamoxifen treatment in xenograft BALB/c nude mice. Dehydroeburicoic acid (2) was characterized as the main chemical constituent in AC-3E against breast cancer.
CONCLUSION: This study suggests that AC-3E extracts can be employed as a double-barreled approach to treat human ER+ breast cancer by attacking both cancer cells and tumor-associated blood vessel cells.
AIM OF THE STUDY: This study is designed to investigate the vasorelaxation effect of G. uralensis from various extracts and to study its pharmacology effect.
MATERIALS AND METHODS: The vasorelaxation effect of G. uralensis extracts were evaluated on thoracic aortic rings isolated from Sprague Dawley rats.
RESULTS: Among these three extracts of G. uralensis, 50% ethanolic extract (EFG) showed the strongest vasorelaxation activity. EFG caused the relaxation of the aortic rings pre-contracted with phenylephrine either in the presence or absence of endothelium and pre-contracted with potassium chloride in endothelium-intact aortic ring. Nω-nitro-L-arginine methyl ester, methylene blue, or 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one inhibit the vasorelaxation effect of EFG in the presence of endothelium. On the other hand, in the presence of the potassium channel blockers (tetraethylammonium and barium chloride), the vasorelaxation effect of EFG was not affected, but glibenclamide and 4-aminopyridine did inhibit the vasorelaxation effect of EFG. With indomethacin, atropine and propranolol, the vasorelaxation effect by EFG was significantly reduced. EFG was also found to be effective in reducing Ca(2+) release from sarcoplasmic reticulum and the blocking of calcium channels.
CONCLUSIONS: The results obtained suggest that EFG is involved in the NO/sGC/cGMP pathway.
MATERIALS AND METHODS: Three populations were retrospectively examined. Group 1 included 1,137 consecutive18F-FDG PET/CT studies and was used to determine the prevalence of focal uptake at the RI or IC. Group 2 included 361 cases from a 10-year period with18F-FDG PET/CT and MRI of shoulder performed within 45 days of each other and was used to enrich the study group. Group 3 included 109 randomly selected patients from the same time frame as groups 1 and 2 and was used to generate the control group. The study group consisted of 15 cases from the three groups, which had positive PET findings. PET/CT images were assessed in consensus by two musculoskeletal radiologists. The reference standard for a diagnosis of AC was clinical and was made by review of the medical record by a pain medicine physician.
RESULTS: The prevalence of focal activity at either the RI or IC ("positive PET") was 0.53%. Nine patients had a clinical diagnosis of AC and 15 patients had a positive PET. The sensitivity and specificity of PET for detection of AC was 56% and 87%, respectively. PET/CT had a positive likelihood ratio for AC of 6.3 (95% CI: 2.8-14.6).
CONCLUSIONS: Increased uptake at the RI or IC on PET/CT confers a moderate increase in the likelihood of AC.