Mucosal loss with increased expression of IL-6, IL-8, and COX-2 in a formula-feeding only neonatal rat model of necrotizing enterocolitis

Introduction

The aim of our study is to establish a reliable neonatal rat model by formula feeding only for evaluation of early surgical intervention on the course of experimental necrotizing enterocolitis (NEC).

Material and methods

Newborn Sprague–Dawley rats were divided into 50 breast-fed (group 1) and 38 formula fed (Similac/Esbilac, group 2) animals. The pups were sacrificed on the 4th, 5th, and 6th day of life and the terminal intestine examined for macroscopic and histologic changes as well as cytokine expression.

Results

The histological mucosal damage was significantly higher of group 2 compared to group 1. The area of the vital mucosa of group 2 was significantly (58.57%, p < 0.001) lower compared to group 1 (75.12%). The mRNA expression of the inflammatory cytokines IL-6, IL-8 and COX-2 was significantly 2-, 5- and 10-fold increased in group 2 compared to group 1.

Discussion

Formula fed newborn rats displayed an inflammatory enterocolitis similar to human NEC. Our study demonstrates a significant loss of mucosa in animals with NEC having increased expression levels of IL-6, IL-8 and COX-2. Mucosal loss appears to be a distinct feature of experimental NEC and has to be correlated with the human disease.     

Difficulties experienced in defining the microbial cause of pelvic inflammatory disease

Clinical assessment of women with pelvic pain was a poor indicator of disease seen at laparoscopy. Thus, of 109 women, 22 at laparoscopy had salpingitis, 19 had adhesions without salpingitis, 20 had endometriosis or ovarian pathology and 48 no observable abnormality. In all laparoscopic categories, Ureaplasma spp. and Mycoplasma hominis, but not Mycoplasma genitalium, were at least as common in the cervix/vagina as Chlamydia trachomatis and equally frequent in the endometrium. However, C. trachomatis had the greatest propensity for spread to the Fallopian tubes. Thus, of 28 women who had C. trachomatis organisms in the vagina/cervix, 13 had them in a Fallopian tube (ratio 2.2:1); the ratio was 6:1 for Neisseria gonorrhoeae, 8:1 for M. genitalium, 21:1 for M. hominis and 31:1 for Ureaplasma spp. M. hominis organisms in a large number were detected most often in women with salpingitis. The likelihood of spread of Ureaplasma urealyticum and U. parvum from the lower to the upper genital tract was about the same and they were detected only once each in a tube, which was not inflamed in either case. Multiple bacteria were often detected at a single site, making it difficult to establish the exact cause of disease. However N. gonorrhoeae was considered to be the sole cause of salpingitis in one woman and the primary or equal primary contributor in four others; C. trachomatis was involved in at least 11 women, mostly as the sole cause or as the primary contributor; M. genitalium was considered the cause in one woman and had possible involvement in three others; and M. hominis was a questionable sole cause in one woman and the primary or equal primary contributor in three. Serologically, C. trachomatis was related to adhesions, without salpingitis, more often (63%) than any other micro-organism. M. genitalium may have been implicated in one case. Serologically, a previous C. trachomatis infection was indicated in 40% of women without an observable laparoscopic abnormality. C. trachomatis in the endometrium and tubes of women without any laparoscopic abnormality suggests subclinical disease, endometritis or endosalpingitis. There was evidence for a smaller proportion (19%) of women without an abnormality having been infected previously with M. genitalium. To some extent this is consistent with the infrequency of acute M. genitalium infections in this cohort of women.     

Histone deacetylase inhibitors as potential therapeutic approaches for chordoma: An immunohistochemical and functional analysis

Chordomas are rare malignancies of the axial skeleton. Therapy is mainly restricted to surgery. This study investigates histone deacetylase (HDAC) inhibitors as potential therapeutics for chordomas. Immunohistochemistry (IHC) was performed using the HDAC 1–6 antibodies on 50 chordoma samples (34 primary tumors, 16 recurrences) from 44 patients (27 male, 17 female). Pan‐HDAC‐inhibitors Vorinostat (SAHA), Panobinostat (LBH‐589), and Belinostat (PXD101) were tested for their efficacy in the chordoma cell line MUG‐Chor1 via Western blot, cell cycle analysis, caspase 3/7 activity (MUG‐Chor1, UCh‐1), cleaved caspase‐3, and PARP cleavage. p‐Values below 0.05 were considered significant. IHC was negative for HDAC1, positive for HDAC2 in most (n = 36; 72%), and for HDACs 3–6 in all specimens available (n = 43; 86%). HDAC6 expression was strongest. SAHA and LBH‐589, but not PXD101 caused a significant increase of G2/M phase cells and of cleaved caspase‐3 (p = 0.0003, and p = 0.0014 after 72 h, respectively), and a peak of caspase 3/7 activity. PARP cleavage confirmed apoptosis. The presented chordoma series expressed HDACs 2–6 with strongest expression of HDAC6. SAHA and LBH‐589 significantly increased apoptosis and changed cell cycle distribution in vitro. HDAC‐inhibitors should be further evaluated as therapeutic options for chordoma. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1999–2005, 2013     

Effect of platelet‐rich plasma on the biologic activity of the human rotator‐cuff fibroblasts: A controlled in vitro study

To assess the in vitro effect of platelet‐rich plasma (PRP) on biological activity of the human rotator cuff fibroblasts and to describe the optimal dose‐response to maximize cellular stimulation while reducing potential risk. Rotator cuff (RC) fibroblasts of n = 6 patients (mean age of 65.2 years) undergoing arthroscopic cuff tear reconstruction were cultured in vitro for 21 days and stimulated with PRP in three different concentrations (1‐, 5‐, and 10‐fold). Samples were obtained for DNA and GAG measurement at 1, 7, 14, and 21 days. The biological outcomes were regressed on the PRP concentration. The application of PRP significantly influenced the fibroblast proliferation and activity of the human rotator cuff with elevated glycosaminoglycan (GAG) and DNA levels. The dosage of PRP had the significantly highest impact on this proliferation using a onefold or fivefold application. PRP has a significant effect on fibroblast proliferation of the human rotator cuff in vitro with an optimal benefit using a onefold or fivefold PRP concentration. This study justifies further in vivo investigations using PRP at the human rotator cuff. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1249–1253, 2013     

The rational of forehead lifting in patients with chronic facial paralysis

Background

The incidence of permanent facial sequels in patients with Bell’s palsy is about 30 % and results in impaired mimic expression of both midface and forehead in varying degrees. Even at rest, most patients experience an imbalance of their facial features. In this article, static correction of brow imbalance was evaluated in patients with sequels after unilateral facial palsy.

Methods

Thirty-one patients with sequels of Bell’s palsy underwent surgery with endoscopic forehead lift. Brow position was geometrically assessed pre- and postoperatively. The validated self-assessment instrument for quality of life [Short Form 36(SF-36)] was completed prior to and after surgery. The follow-up period was 12 months.

Results

A notable improvement in the position of the brows was demonstrated over time with lasting results. All patients experienced an improvement in facial symmetry and balance at rest. However, no significant difference could be shown using SF-36 pre- and postoperatively.

Conclusion

Endoscopic forehead lift combined or as an isolated procedure is a valuable instrument to correct sequels of Bell’s palsy. Level of Evidence: Level IV, therapeutic study.     

Increased radial glia quiescence,decreased reactivation upon injury and unaltered neuroblast behavior underlie decreased neurogenesis in the aging zebrafish telencephalon

The zebrafish has recently become a source of new data on the mechanisms of neural stem cell (NSC) maintenance and ongoing neurogenesis in adult brains. In this vertebrate, neurogenesis occurs at high levels in all ventricular regions of the brain, and brain injuries recover successfully, owing to the recruitment of radial glia, which function as NSCs. This new vertebrate model of adult neurogenesis is thus advancing our knowledge of the molecular cues in use for the activation of NSCs and fate of their progeny. Because the regenerative potential of somatic stem cells generally weakens with increasing age, it is important to assess the extent to which zebrafish NSC potential decreases or remains unaltered with age. We found that neurogenesis in the ventricular zone, in the olfactory bulb, and in a newly identified parenchymal zone of the telencephalon indeed declines as the fish ages and that oligodendrogenesis also declines. In the ventricular zone, the radial glial cell population remains largely unaltered morphologically but enters less frequently into the cell cycle and hence produces fewer neuroblasts. The neuroblasts themselves do not change their behavior with age and produce the same number of postmitotic neurons. Thus, decreased neurogenesis in the physiologically aging zebrafish brain is correlated with an increasing quiescence of radial glia. After injuries, radial glia in aged brains are reactivated, and the percentage of cell cycle entry is increased in the radial glia population. However, this reaction is far less pronounced than in younger animals, pointing to irreversible changes in aging zebrafish radial glia. J. Comp. Neurol. 521: 3099–3115, 2013. © 2013 Wiley Periodicals, Inc.     

Endoscopic neurosurgery in preterm and term newborn infants—a feasibility report

Objective

Neuroendoscopic procedures became essential in neurosurgical treatment of disturbed cerebrospinal fluid dynamics. While a vast number of papers report on the neuroendoscopic experience for adults and children, no series so far reported on techniques and indications for neonate infants. We present our experience for the feasibility of neuroendoscopic procedures in preterm and term newborn infants.

Methods

All preterm and term infants who underwent an endoscopic neurosurgical intervention prior to the 28th day after the previously estimated date of delivery were identified by retrospective review. Surgical procedures and techniques, complications, and further follow-up data are reported.

Results

During the study period, 14 infants (median age at surgery, 36+²/7 weeks of gestation) underwent 20 endoscopic procedures. The performed procedures included endoscopic septostomy (n?=?3), endoscopic shunt placement for multiloculated hydrocephalus (n?=?4), endoscopic transaqueductal stenting for isolated fourth ventricle (n?=?3), and endoscopic lavage for ventriculitis (n?=?4) or for intraventricular hemorrhage (n?=?6). No severe complications were seen, while two patients necessitating unexpected interventions during further follow-up (10 %).

Conclusions

Despite the fragility of preterm and term newborn infants, neuroendoscopic procedures may play an important role in the treatment of disturbed cerebrospinal fluid (CSF) dynamics also in this patient population. The neuroendoscopic approach may be curative in conditions like isolated lateral ventricle, may facilitate simplified and effective CSF diversion in multiloculated hydrocephalus or isolated fourth ventricle, and may be beneficial in the course of ventriculitis and intraventricular hemorrhage. Further studies must verify our experience with a bigger cohort of patients and on a multicenter basis.