Successful primate immunization with peptides conjugated to purified protein derivative or mycobacterial heat shock proteins in the absence of adjuvants

We have previously shown in mice that antibodies can be induced to synthetic malaria peptides conjugated to mycobacterial antigens, such as purified protein derivative (PPD) or heat shock proteins (hsp), and given in the absence of adjuvants after a previous priming with bacille Calmette—Guérin (BCG). In the present study we investigated this model of immunization in the non-human primates, Saimiri sciureus monkeys. Monkeys primed with BCG subcutaneously and then immunized subcutaneously with the Plasmodium falciparum sporozoite (NANP)₄₀ synthetic peptide conjugated to PPD or mycobacterial hsp of 65 or 70 kD, in the absence of adjuvants, produced anti-peptide and anti-sporozoite IgG antibodies. Interestingly, the carrier effect of the hsp of 70 kD for the induction of anti-(NANP)₄₀ antibodies was also observed in the absence of a previous priming with BCG. These data suggest that such a vaccination strategy may be applied to humans.     

MR imaging of neurocysticercosis

Magnetic resonance (MR) was performed in 50 patients with neurocysticercosis. Comparison was made with other neuroradiological imaging modalities including CT, myelography, CT ventriculography, and CT myelocisternography. Eighteen patients were found to have intraventricular cysts. In several patients, these were multiple and 22 intraventricular cysts were discovered. Although 4 of the 22 ventricular cysts were missed by MR, T1-weighted images can play a significant role in the early detection of intraventricular cysticercosis cysts, showing the cyst wall (9 of 22), a high intensity mural nodule (6 of 22), and increased signal intensity of the cyst fluid (5 of 22). Cisternal cysts (14 cysts in 10 patients) could be identified; they appear similar to intraventricular cysts, but mural nodules are infrequently seen (1 of 14). Twenty-nine patients had 69 parenchymal cysts. An attempt was made to assess the viability of these parenchymal lesions by matching the CT and MR findings with the Escobar pathologic staging system. Neuroimaging findings seemed compatible with early parenchymal lesions in the vesicular stage in 11 instances. Findings in cases with later stage cysts tend to support the concept that a dying larva provokes pronounced inflammatory reaction in the adjacent brain. Computed tomography remains the superior modality for depicting parenchymal calcifications within dead larvae. A case of a spinal cysticercosis cyst demonstrated with MR (in a patient with extensive intracranial cisternal cysts and a fourth ventricular cyst) is described.     

Is complete resection of the aganglionic bowel in extensive total aganglionosis up to the middle ileum always necessary?

Background/Purpose

Total colonic aganglionosis is an unusual form of Hirschsprung disease, reflected by the small number of published case studies. The goal of this study was to analyze our cases of the last 22 years and report on our experience with 3 cases of extended total aganglionosis proximal to the middle ileum in which remaining aganglionic bowel was left in situ.

Materials and Methods

In a period of 22 years (from January 1988 to April 2010), we operated on 15 children with total aganglionosis. These children were among 163 children with Hirschsprung disease. In 3 patients with extended aganglionosis proximal to the middle ileum, remaining aganglionic bowel was left in situ. Data were collected from the medical records, including each patient's demographics, medical history, primary treatment, complications, and follow-up.

Results

Eleven of the 15 children received an ileostomy as first treatment, and 4 children underwent a primary Duhamel procedure. Early postoperative complications included an abscess after an open procedure in a patient with trisomy 21 syndrome and an incorrect leveling resection that required an ileostomy. There were 2 deaths at 6 and 16 months postoperatively. The mortality rate was 13.3%. Of the 15 patients, 7 (46%) presented with at least 1 episode of postoperative enterocolitis, and only 2 of these patients had more than 3 episodes. We treated 3 patients with extended aganglionosis up to midileum (20%) in which the proximal resection level was in the aganglionic segment of ileum at the level of the ileostomy. The ileostomies were shown to be functioning satisfactorily before the pull through, so going more proximal to the ileostomy might have meant that the patient would present short bowel problems. These 3 patients had good bowel function postoperatively.

Conclusion

In principle, resection of the aganglionic bowel is mandatory to relieve obstruction and subsequent complications. There are situations, however, where the complications of a short bowel begin to outweigh the benefits of resection. In these cases, leaving remaining aganglionic bowel in situ may be an advantageous option for the patients with total aganglionosis extending to the midileum whose ileostomy functions well.     

Indwelling esophageal balloon catheter for benign esophageal stenosis in infants and children

Background

Balloon dilatation of benign esophageal strictures is an established mode of therapy in adults and children. There remains a group of patients with refractory stenosis despite dilatation at regular intervals. An indwelling balloon catheter may offer an alternative.

Methods

This is a retrospective study of 19 children who underwent esophagoscopy between 2004 and 2012 with placement of an indwelling balloon catheter for refractory esophageal stenosis. Total number of endoscopies, number of endoscopies with indwelling balloon catheter, as well as complications, reoperations, and mortality due to use of the balloon catheter were studied.

Results

Patient age ranged from 4 weeks to 15 years. The indwelling balloon catheter was used to treat refractory stenosis after corrective surgery of long gap esophageal atresia (n = 5), esophageal atresia with distal fistula (n = 2), refractory esophageal stenosis due to caustic esophageal burns (n = 7), reflux (n = 2), and stenosis of unknown cause (n = 3). With the indwelling balloon catheter in place, the mean number of endoscopies equalled four. Complications were restenosis after a symptom-free period for which a new indwelling balloon catheter was necessary (n = 3). Two others needed two to five additional dilations: balloon leakage requiring replacement (n = 7 in 5 patients), sputum retention (n = 1), and dislodgement (n = 5 in 4 patients). More importantly, there was no mortality or the need for any patient to undergo a surgical resection.

Conclusions

The indwelling balloon catheter is safe to use and can be used by parents at home. More importantly it obviates the need for rethoracotomy/-scopy or esophageal replacement.     

A pre‐clinical functional assessment of an acellular scaffold intended for the treatment of hard‐to‐heal wounds

The majority of the population experience successful wound‐healing outcomes; however, 1–3% of those aged over 65 years experience delayed wound healing and wound perpetuation. These hard‐to‐heal wounds contain degraded and dysfunctional extracellular matrix (ECM); yet, the integrity of this structure is critical in the processes of normal wound healing. Here, we evaluated a novel synthetic matrix protein for its ability to act as an acellular scaffold that could replace dysfunctional ECM. In this regard, the synthetic protein was subjected to adsorption and diffusion assays using collagen and human dermal tissues; evaluated for its ability to influence keratinocyte and fibroblast attachment, migration and proliferation and assessed for its ability to influence in vivo wound healing in a porcine model. Critically, these experiments demonstrate that the matrix protein adsorbed to collagen and human dermal tissue but did not diffuse through human dermal tissue within a 24‐hour observation period, and facilitated cell attachment, migration and proliferation. In a porcine wound‐healing model, significantly smaller wound areas were observed in the test group compared with the control group following the third treatment. These data provide evidence that the synthetic matrix protein has the ability to function as an acellular scaffold for wound‐healing purposes.     

柴胡皂甙m和柴胡皂甙n的结构鉴定

从黑柴胡(Bupleurum smithii Wolff)根中分得二个新三萜皂甙。根据理化性质和波谱数据,分别鉴定为3β,23,28-三羟基齐墩果烷-11,13(18)-二烯-3-O-β-D-吡喃葡萄糖基-(1→3)-β-D-吡喃呋糖甙,命名为柴胡皂甙m(saikosaponin m,IV),和3β,16β,23,28-四羟基齐墩果烷-11,13(18)-二烯-3-O-β-D-吡喃葡萄糖基-(1→6)-[α-L-吡喃鼠李糖基-(1→4)]-β-D-吡喃葡萄糖甙,命名为柴胡皂甙n(saikos-aponinn,IX)。     

刺果甘草化学成分的研究

从刺果甘草(Glycyrrhiza pallidiflora Maxim)的根和根茎中分离到五种化合物,经理化性质和光谱方法鉴定,化合物P-2为4-羟基-2,4’-二甲氧基查尔酮,为一新的化合物,命名为刺果甘草查尔酮(glypallichalcone,P-2)。其它分别为4'-O-methyl-coumestrol(P-1),谷氨酸乙酰化物(N-acetylglutamicacid,P-3)和芒柄花素(formononetin,P-4),均为首次从该植物中获得。此外还得到β-谷甾醇(β-sitos-terol,P-5)     

Exchange protein activated by cyclic AMP 2 (Epac2) plays a specific and time‐limited role in memory retrieval

Knowledge on the molecular mechanisms involved in memory retrieval is limited due to the lack of tools to study this stage of the memory process. Here we report that exchange proteins activated by cAMP (Epac) play a surprisingly specific role in memory retrieval. Intrahippocampal injection of the Epac activator 8‐pCPT‐2′O‐Me‐cAMP was shown to improve fear memory retrieval in contextual fear conditioning whereas acquisition and consolidation were not affected. The retrieval enhancing effect of the Epac activator was even more prominent in the passive avoidance paradigm. Down‐regulation of Epac2 expression in the hippocampal CA1 area impaired fear memory retrieval when the memory test was performed 72 h after training, but not when tested after 17 days. Our data thus identify an important time‐limited role for hippocampal Epac2 signaling in cognition and opens new avenues to investigate the molecular mechanisms underlying memory retrieval. © 2009 Wiley‐Liss, Inc.     

Effects of ramelteon on insomnia symptoms induced by rapid,eastward travel

ObjectiveRamelteon, an MT₁/MT₂ melatonin receptor agonist, was evaluated for its ability to reduce sleep-onset difficulties associated with eastward jet travel.MethodsHealthy adults (n = 110) with a history of jet lag sleep disturbances were flown eastward across five time zones from Hawaii to the east coast of the US. Ramelteon 1, 4, or 8 mg or placebo was administered 5 min before bedtime (local time) for four nights. Sleep parameters were measured using polysomnography (PSG) on Nights 2, 3, and 4. Next-day residual effects were assessed using psychomotor and memory function tests.ResultsCompared to placebo, there was a significant decrease in mean latency to persistent sleep (LPS) on Nights 2–4 with ramelteon 1 mg (?10.64 min, P = 0.030). No consistent significant differences were observed with ramelteon vs. placebo on measures of next-day residual effects except on Day 4 where participants in all ramelteon groups performed significantly worse on the immediate memory recall test compared with placebo (P ? 0.05). The incidence of adverse events was similar for ramelteon and placebo.ConclusionAfter a 5-h phase advance due to eastward jet travel, ramelteon 1 mg taken before bedtime for four nights reduced mean LPS relative to placebo in healthy adults.