CA-125 elimination rate constant K (KELIM) as a promising predictor of complete cytoreduction after neoadjuvant chemotherapy in advanced ovarian cancer patients: a retrospective study from two Chinese hospitals.

BACKGROUND: The modeled CA-125 elimination constant K (KELIM) is a potential marker of tumor chemosensitivity in ovarian cancer patients treated with neoadjuvant chemotherapy (NACT) before interval surgery. The objective of this study was to externally validate the KELIM (rate of elimination of CA-125) score in patients with high-grade serous ovarian cancer (HGSC) undergoing NACT and explore its relation to the completeness of IDS and survival. METHODS: The study was based on a retrospective cohort of 133 patients treated for advanced HGSC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV, with neoadjuvant chemotherapy, folllowed by interval surgery, in two centres in China. CA-125 concentrations at baseline and during neoadjuvant chemotherapy were collected. We used standardized (std) KELIM for subsequent analysis. Clinicopathologic parameters were collected, and Kaplan‒Meier survival analyses were performed for PFS and OS. RESULTS: KELIM was an independent predictor of the probability of complete surgery and survival in our cohort. The median std KELIM score of patients with complete surgery was significantly higher than that of patients with incomplete IDS (1.20 vs. 0.71, P < 0.001). Multivariate analysis showed that a std KELIM score ≥0.925 was an independent predictive factor for achieving complete resection (OR = 5.480; 95% CI, 2.409-12.466, P < 0.001) and better PFS (HR = 0.544; 95% CI: 0.349-0.849, P = 0.007) and OS (HR = 0.484; 95% CI: 0.251-0.930, P = 0.030). CONCLUSIONS: The tumor-primary tumor chemosensitivity, assessed by the modeled CA-125 KELIM, calculated during NACT, is a major parameter to consider for decision-making regarding IDS attempts and predicting patient survival.

Association between Age of Menopause and Thickness of Crestal Cortical Bone at Dental Implant Site: A Cross-Sectional Observational Study.

Satisfactory host bone quality and quantity promote greater primary stability and better osseointegration, leading to a high success rate in the use of dental implants. However, the increase in life expectancy as a result of medical advancements has led to an aging population, suggesting that osteoporosis may become a problem in clinical dental implant surgery. Notably, relative to the general population, bone insufficiency is more common in women with post-menopausal osteoporosis. The objective of this study was to compare the thickness of the crestal cortical bone at prospective dental implant sites between menopausal and non-menopausal women. Prospective dental implant sites in the jawbone were evaluated in two groups of women: a younger group (<50 years old), with 149 sites in 48 women, and an older group (>50 years old) with 191 sites, in 37 women. The thickness of the crestal cortical bone at the dental implant site was measured based on each patient's dental cone-beam computed tomography images. For both groups, one-way analysis of variance and Tukey's post-test were used to assess the correlation between cortical bone thickness and the presence of implants in the four jawbone regions. Student's t-test was further used to compare differences between the older and younger groups. From the retrospective study results, for both groups, thickness of the crestal cortical bone was the highest in the posterior mandible, followed by anterior mandible, anterior maxilla, and posterior maxilla. Compared with the younger group, the older group had a lower mean thickness of the crestal cortical bone. Among the four regions, however, only in the posterior maxilla was the crestal cortical bone significantly thinner in the older group than in the younger group.

Adrenomedullin gene delivery is cardio-protective in a model of chronic nitric oxide deficiency combining pressure overload, oxidative stress and cardiomyocyte hypertrophy.

BACKGROUND/AIMS: Chronic inhibition of nitric oxide (NO) synthesis is associated with hypertension, myocardial ischemia, oxidative stress and hypertrophy; expression of the vasodilator peptide, adrenomedullin (AM) and its receptors is augmented in cardiomyocytes, indicating that the myocardial AM system may be activated in response to pressure loading and ischemic insult to serve a counter-regulatory, cardio-protective role. The study examined the hypothesis that oxidative stress and hypertrophic remodeling in NO-deficient cardiomyocytes are attenuated by adenoviral vector-mediated delivery of the human adrenomedullin (hAM) gene in vivo. METHODS: The NO synthesis inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 15mg . kg(-1) . day(-1)) was given to rats for 4 weeks following systemic administration via the tail vein of a single injection of either adenovirus harbouring hAM cDNA under the control of the cytomegalovirus promoter-enhancer (Ad.CMV-hAM-4F2), or for comparison, adenovirus alone (Ad.Null) or saline. Cardiomyocytes were subsequently isolated for assessment of the influence of each intervention on parameters of oxidative stress and hypertrophic remodelling. RESULTS: Cardiomyocyte expression of the transgene persisted for > or =4 weeks following systemic administration of adenoviral vector. In L-NAME treated rats, relative to Ad.Null or saline administration, Ad.CMV-hAM-4F2 (i) reduced augmented cardiomyocyte membrane protein oxidation and mRNA expression of pro-oxidant (p22phox) and anti-oxidant (SOD-3, GPx) genes; (ii) attenuated increased cardiomyocyte width and mRNA expression of hypertrophic (sk-alpha-actin) and cardio-endocrine (ANP) genes; (iii) did not attenuate hypertension. CONCLUSIONS: Adenoviral vector mediated delivery of hAM resulted in attenuation of myocardial oxidative stress and hypertrophic remodelling in the absence of blood pressure reduction in this model of chronic NO-deficiency. These findings are consistent with a direct cardio-protective action in the myocardium of locally-derived hAM which is not dependant on NO generation.

A 70-kDa molecular chaperone, DnaK, from the industrial bacterium Bacillus licheniformis: gene cloning, purification and molecular characterization of the recombinant protein.

The heat shock protein 70 (Hsp70/DnaK) gene of Bacillus licheniformis is 1,839 bp in length encoding a polypeptide of 612 amino acid residues. The deduced amino acid sequence of the gene shares high sequence identity with other Hsp70/DnaK proteins. The characteristic domains typical for Hsps/DnaKs are also well conserved in B. licheniformis DnaK (BlDnaK). BlDnaK was overexpressed in Escherichia coli using pQE expression system and the recombinant protein was purified to homogeneity by nickel-chelate chromatography. The optimal temperature for ATPase activity of the purified BlDnaK was 40°C in the presence of 100 mM KCl. The purified BlDnaK had a V(max) of 32.5 nmol Pi/min and a K(M) of 439 µM. In vivo, the dnaK gene allowed an E. coli dnaK756-ts mutant to grow at 44°C, suggesting that BlDnaK should be functional for survival of host cells under environmental changes especially higher temperature. We also described the use of circular dichroism to characterize the conformation change induced by ATP binding. Binding of ATP was not accompanied by a net change in secondary structure, but ATP together with Mg(2+) and K(+) ions had a greater enhancement in the stability of BlDnaK at stress temperatures. Simultaneous addition of DnaJ, GrpE, and NR-peptide (NRLLLTG) synergistically stimulates the ATPase activity of BlDnaK by 11.7-fold.

[Protective effect and mechanism of IPQDS on acute myocardial infarction in rats].

OBJECTIVE: To observe the protective effect of Injection of Panax quinquefolium diolsaponins (IPQDS) and its mechanism on acute myocardial infarction in rats. METHOD: The acute myocardial infarct model was prepared by left anterior descending coronary occulusion for 24 hours in open chest anesthetized rats. The myocardial infarct size (MIS) was calculated. The activities of serum creatine hosphokinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the contents of malondialdehyde (MDA) and nitric oxide (NO) were determined. Blood was collected to observe low shearing specific viscosity, middle shearing specific viscosity and high shearing specific viscosity of whole blood and plasma viscosity. At the same time, the platelet aggregation rate and platelet adherence rate were also determined. RESULT: In rats treated by IPQDS (in a dosage of 12.5, 25 and 50 mg x kg(-1) d, i.p. 3d ), the MIS was significantly reduced. The activities of serum CK, LDH and AST, and the content of serum MDA were declined. The activities of SOD and GSH-Px, and the content of NO were increased markedly. In addition, low shearing specific viscosity, middle shearing specific viscosity and high shearing specific viscosity of whole blood and plasma viscosity as well as platelet aggregation rate were also declined significantly. But platelet adherence rate had no significant change. CONCLUSION: IPQDS has a protective effect on acute myocardial ischemia, which may be related to increasing activity of antioxidase in body, scavenging the damage of peroxidation from oxygen free radicals, decreasing the viscosity of blood and plasma and preventting thrombosis etc.

SRIF receptor subtype expression and involvement in positive and negative contractile effects of somatostatin-14 (SRIF-14) in ventricular cardiomyocytes.

BACKGROUND/AIMS: Somatostatin-14 (SRIF-14), a neuropeptide co-stored with acetylcholine in the cardiac parasympathetic innervation, exerts both positive and negative influences directly on contraction of ventricular cardiomyocytes, indicative of involvement of more than one of five known SRIF (SSTR) receptor subtypes. The aim was to characterize receptor subtype expression in adult rat ventricular cardiomyocytes and to investigate the influence of a series of SRIF (SSTR) subtype-selective agonists on contractile parameters. METHODS: mRNA and protein expression of each receptor subtype were quantified by RT-PCR and immunoblotting respectively; for contraction studies, cells were stimulated at 0.5 Hz under basal conditions and in the presence of isoprenaline (ISO, 10(-8)M). RESULTS: all five SRIF (SSTR) receptor subtypes were expressed in cardiomyocytes although SRIF1A (SSTR2) and SRIF2A (SSTR1) were less abundant than the other subtypes. L803087 (10(-8)M), a SRIF2B (SSTR4) agonist, attenuated ISO-stimulated peak contractile amplitude and prolonged relaxation time (T(50)). L796778 (10(-7)M), a SRIF1C (SSTR3) agonist, augmented basal and ISO-stimulated peak contractile amplitude; L779976 (10(-8)M) and L817818 (10(-9)M), agonists at SRIF1A (SSTR2) and SRIF1B (SSTR5) receptors, respectively, also augmented ISO-stimulated peak amplitude. CONCLUSION: These data support involvement of SRIF2B (SSTR4) receptors in the negative contractile effects of SRIF-14, while one or more of the three SRIF1 receptor subtypes (SSTR2, 3 or 5) may contribute to the positive contractile effects of SRIF-14.

Tissue engineering of biphasic cartilage constructs using various biodegradable scaffolds: an in vitro study.

Biological restoration of osteochondral defects requires suitable subchondral support material that also allows the induction of hyaline cartilage tissue. Biphasic implants consisting of pre-fabricated neocartilage and an underlying biodegradable osteoconductive base may meet these requirements. Here we explore various candidate biodegradable support materials onto which neo-cartilage was produced in vitro. Porcine chondrocytes were seeded in a closed and static bioreactor with a base of biomaterial consisting of either poly-L-lactide [P(L)LA], poly-d,l-lactide [P(D,L)LA] or Collagen-hydroxyapatite [Col-HA] and were cultured for 15 weeks. Viable neo-cartilage was produced on each biomaterial with differing amounts of cellular colonisation. P(D,L)LA breakdown was more rapid and uneven among the three biomaterials, leading to constructs of irregular shape. Little or no breakdown or chondrocyte colonisation was evident in P(L)LA. Col-HA constructs were superior in terms of viability, implant morphology and integration between neo-cartilage and biomaterial. These results indicate that our reported system has potential for producing biphasic implants that may be adequate for the repair of osteochondral defects.