[Effects of cardiac resynchronization therapy in patients with advanced congestive heart failure evaluated by real-time 3-dimensional echocardiography].

OBJECTIVE: To quantitatively assess the effects of cardiac resynchronization therapy (CRT) in patients with advanced congestive heart failure by real-time 3-dimensional(3D) echocardiography (RT-3DE). METHODS: Eighteen patients with advanced congestive heart failure underwent CRT with New York Heart association(NYHA) class III and IV and wide QRS complex (>120 ms) were included (17 dilated cardiomyopathy and 1 ischemic cardiomyopathy). Before CRT and 8 months after CRT, the clinical and RT-3DE parameters and outcome were analyzed. RESULTS: The biventricular pacemaker was successfully implanted in 17 patients (94.4%). Compared with before CRT, NYHA class of patients decreased by 1.5 class (P < 0.01), left ventricular ejection fraction increased by 25% (P < 0.01), left ventricular end systolic volume decreased by 38% (P < 0.01), left ventricular systolic dyssynchrony index (SDI) improved significantly (14.2% before CRT vs. 9.8% after CRT, P < 0.01 ) post CRT. Change in SDI and change in LVEF was positively correlated (r = 0.62, P < 0.01) . The procedure complications and outcome during and after CRT included coronary sinus dissection (n = 1), left ventricular lead dislodgement (n = 1), phrenic nerve stimulation (n = 1), sudden cardiac death (n = 1). Three non-response patients were complicated with atrial fibrillation, nonspecific intraventricular block and dilated cardiomyopathy with postero-lateral scar tissue. CONCLUSIONS: CRT could improve the cardiac function, correct the mechanical desynchronization and reverse left ventricular remodeling in patients with congestive heart failure, and SDI quantification by RT-3DE could predict increase of LVEF after CRT, however, there were complications related to the implantation procedure and possibilities of non-response.

Specific alterations in gut microbiota are associated with prognosis of Budd-Chiari syndrome.

Gut microbiota is associated with liver diseases. However, gut microbial characteristics of Budd-Chiari syndrome (B-CS) have not been reported. Here, by MiSeq sequencing, gut microbial alterations were characterized among 37 health controls, 20 liver cirrhosis (LC) patients, 31 initial B-CS patients (B-CS group), 33 stability patients after BCS treatment (stability group) and 23 recurrent patients after BCS treatment (recurrence group). Gut microbial diversity was increased in B-CS versus LC. Bacterial community of B-CS clustered with controls but separated from LC. Operational taxonomic units (OTUs) 421, 502 (Clostridium IV) and 141 (Megasphaera) were unique to B-CS. Genera Escherichia/Shigella and Clostridium XI were decreased in B-CS versus controls. Moreover, nine genera, mainly including Bacteroides and Megamonas, were enriched in B-CS versus LC. Notably, Megamonas could distinguish B-CS from LC with areas under the curve (AUCs) of 0.7904. Microbial function prediction revealed that L-amino acid transport system activity was decreased in B-CS versus both LC and controls. Furthermore, OTUs 27 (Clostridium XI), 137 (Clostridium XIVb) and 40 (Bacteroides) were associated with B-CS stability. Importantly, genus Clostridium XI was enriched in stability group versus both recurrence group and B-CS group. Also, PRPP glutamine biosynthesis was reduced in stability group versus recurrence group, but was enriched in stability group versus B-CS group. In conclusion, specific microbial alterations associated with diagnosis and prognosis were detected in B-CS patients. Correction of gut microbial alterations may be a potential strategy for B-CS prevention and treatment.

Immunologic protection of anti-tetrodotoxin vaccines against lethal activities of oral tetrodotoxin challenge in mice.

Tetrodotoxin (TTX) is a high toxic small molecular neurotoxin. Haptenic vaccine for TTX was investigated and the carrier proteins were compared. TTX was conjugated to Tachypleus tridentatus hemocyanin (TTH) and tetanus toxoid (TT) via formaldehyde to form the artificial antigen TTX-TTH and TTX-TT. BALB/c mice were immunized with the artificial antigen, the TTX-specific antibody response were detected. The immunized animals were intragastrically challenged with increasing doses of TTX repeatedly. The mice which exposed to TTX in doses of 600, 630, 800, 1200, 1500, 2000 and 2400 microg/kg survived at rates of 100, 100, 90, 90, 80, 50 and 20%, with a LD(50) value of 2020 microg/kg for TTH-TTX vaccine, and of 100%, 90.9%, 90.9%, 90.9%, 63.6%, 27.3% and 0%, with a LD(50) value of 1410 microg/kg for TT-TTX vaccine, respectively. All control mice inoculated with carrier protein TTH or TT uniformly died of a dose of 600 microg/kg TTX i.g. challenge. Animals immunized with vaccines could antagonize repeated TTX challenge, half of them surviving about 6 mg/kg, and a few being able to bear a maximal accumulative dose as high as approximate 9 mg/kg of TTX challenges within eight months. The TTH-TTX vaccine was of the more excellent in protective effect from TTX oral intoxication, mainly resulted from the higher antibody affinity than that from TT-TTX vaccine. The present study for the first time demonstrated that the anti-TTX experimental vaccines would high effectively protect animal from multiple, oral TTX intoxication. Immunoprophylaxis would be the hopeful means against TTX poisoning.

Toxin-neutralizing effect and activity-quality relationship for mice tetrodotoxin-specific polyclonal antibodies.

The polyclonal antibodies specific for tetrodotoxin (TTX) were prepared from mice and their capacity of neutralizing TTX was investigated so as to explore the possibility of developing TTX antitoxin. Haptenic TTX was conjugated to Tachypleus tridentatus hemocyanin (TTH) chemically to form artificial antigen TTX-TTH. BALB/c mice were immunized with TTX-TTH and ascites were induced by intraperitoneal administration of Freund's adjuvant. Twenty strains of TTX-specific ascites antibody with apparent affinity varying from 10(-4) to 10(-7)M were obtained. KM mice were challenged with lethal doses (1LD = 14.0 microg/kg, i.p.) of TTX neutralized by antibodies to evaluate the power of antitoxin. The potential of TTX-neutralizing of the antibodies was approved by the increase in survival animal challenged by lethal doses of TTX pre-incubated in vitro or neutralized in vivo with TTX specific antibodies. The highest protection was observed with all animals survived challenge of 1.5 x LD TTX neutralized in vitro, and antibody administration 4 days prior to 1.3 x LD TTX challenge in vivo neutralization. The protective efficiency was antibody quality factor dependent and with the highest detoxifying immunological equivalent as high as 1 300 microg (TTX)/L(ascites) approximately, while the antibody apparent affinity being at the order of 10(-6) to 10(-7)M. These results suggested that chemical vaccine for haptenic TTX could successfully raise high humoral immune response and the antibodies could neutralize TTX effectively both in vitro and in vivo, antibody therapy would be the hopeful means for detoxification of TTX.

Influence of carrier proteins on the immunologic response to haptenic antitetrodotoxin vaccine.

Tetrodotoxin (TTX) is a haptenic, highly toxic neurotoxin with no specific antidote available yet. Anti-TTX vaccine is being studied for antitoxin development. The effectiveness of the carrier protein in eliciting TTX-specific antibody response was comparatively studied. TTX was conjugated to Tachypleus tridentatus hemocyanin (TTH), Limulus polyphemus hemocyanin (LPH), tetanus toxoid (TT), diphtheria toxoid (DT), and bovine serum albumin (BSA) chemically to form artificial antigens TTH-TTX, LPH-TTX, TT-TTX, DT-TTX, and BSA-TTX, respectively, with which BALB/c mice were immunized, and the antibody response and antitoxic efficacy were detected. The serum anti-TTX antibody response and antitoxic efficacy varied markedly with adopted carrier protein. TTH-TTX elicited the best and BSA-TTX the worst TTX-specific antibody response. The proportion of the immunized mice surviving a 3x lethal dose (LD) dose of TTX challenge was 92%, 75%, 42%, 8%, and 0% for TTH-, TT-, LPH-, DT-, and BSA-TTX conjugates, respectively. The rank order of total efficacy of carrier protein for both anti-TTX antibody response and antitoxic effect was TTH > TT > LPH > DT > BSA. As a result of formaldehyde treatment in coupling of TTX carriers, the relative immunogenicity of TTX vs carrier, that is, the ratio of TTX- to carrier-specific antibody response, evidently varied with respective carrier adopted, in a rank order of TT > BSA > TTH > DT > LPH. The results suggest that the carrier protein used in haptenic TTX vaccine is greatly important in eliciting potent anti-TTX antibody, and both TTH and TT are the preferred carriers for development of excellent experimental TTX vaccine.