Comparison of botulinum toxin type A and aprotinin monotherapy with combination therapy in healing of burn wounds in an animal model

Burns are one of the most common injuries that are complicated by many challenges including infection, severe inflammatory response, excessive expression of proteases, and scar formation. The aim of this study was to investigate the effect of botulinum toxin type A (BO) and aprotinin (AP) separately or in combination (BO-AP) in healing process. Four burn wounds were created in each rat and randomly filled with silver sulfadiazine (SSD), BO, AP and BO-AP. The rats were euthanized after 7, 14, and 28 days, and their harvested wound samples were evaluated by gross pathology, histopathology, gene expression, biochemical testing, and scanning electron microscopy. Both BO and AP significantly reduced expression of interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) at the 7th post wounding day. Moreover, they inhibited scar formation by reducing the TGF-β1 level and increasing basic fibroblast growth factor (bFGF) at the 28th day. AP by decreasing protease production showed more effective role than BO in wound regeneration. AP increased tissue organization and maturation and improved cosmetic appearance of wounds, at 28 days. The best results gained when combination of BO and AP were used in healing of burn wounds. Treatment by BO-AP significantly subsided inflammation compared to the BO, AP, and SSD treated wounds. Treatment with BO-AP also reduced collagen density and led to minimal scar formation. Combination of botulinum toxin type A and aprotinin considerably increased structural and functional properties of the healing wounds by reducing scar formation and decreasing production of proteases.

     

Retrospective analysis of reconstruction techniques after periocular basalioma excision

The paper presents our approach to reconstruction after periocular basalioma (pBCC) excision, especially of large lower lid (LL) and medial canthal (MC) pBCC. Retrospective analysis of data of 123 patients with pBCC, confirmed on histologic examination (HE), operated in period from 1998 to 2006, was performed. Oncologic safety margins of 3 mm were marked after local anesthesia was administered. Reconstruction was done in time of surgery. In pBCC away from a lid margin, adjacent myocutaneous flaps were used. For lid margin involving (LM) pBCC, size of 10 mm and less in horizontal diameter (HD), full-thickness lid excision was performed, combined with lateral canthotomy and/or Tenzel or McGregor flap. When size of LM pBCC was more than 10 mm in HD and it was on a LL, ipsilateral upper lid (UL) tarsoconjunctival (TC) graft combined with single pedicle transposition myocutaneous flap were used. The same size of LM pBCC on a UL required ipsilateral full-thickness LL "switch" flap and/or contralateral LL Hübner graft. In MC pBCC combined approach was used. The follow-up was up to 5 years. The 19 patients (15.4%) had positive tumor margin on HE. Five of them refused further surgery, but only two had recurrence. The rest of 121 patients had no recurrence during follow-up. In 5/14 patients, who underwent additional surgery, no tumor cells were found on HE. The 10/123 patients (8.1%) had complications. The imperative of our approach to reconstruction after pBCC was good functional and cosmetic result, avoiding prolonged lid closure. Accordingly, in large LL LM pBCC we used ipsilateral UL TC graft combined with single pedicle transposition myocutaneous flap. In MC pBCC combined approach was mandatory.     

Role of histone modification and DNA methylation in signaling pathways involved in diabetic retinopathy

Retinopathy, characterized by an alteration of the retinal microvasculature, is a common complication of diabetes mellitus. These changes can cause increased permeability and alter endothelial cell proliferation, edema, and abnormal neovascularization and eventually result in blindness. The pathogenesis of diabetic retinopathy (DR) is complicated, involving many factors/mediators such as genetic susceptibility, microRNAs, and cytokines. One of the factors involved in DR pathogenesis is epigenetic changes that can have a key role in the regulation of gene expression; these include microRNAs, histone modifications, and methylation of DNA. The main epigenetic modifications are DNA methylation and posttranslational modifications of the histones. Generally, the studies on epigenetics can provide new opportunities to investigate the molecular basis of diseases with complicated pathogenesis, including DR, and provide essential insights into the potential design of strategies for its treatment. The aim of this study is an investigation of DR pathogenesis and epigenetic modifications that involve in DR development.     

Kefir Accelerates Burn Wound Healing Through Inducing Fibroblast Cell Migration In Vitro and Modulating the Expression of IL-1ß, TGF-ß1, and bFGF Genes In Vivo

Probiotics and Antimicrobial Proteins - Kefir is a natural probiotic compound with a long history of health benefits which can improve wound healing. This study investigated the regeneration...     

Use of in silico tools for classification of novel missense mutations identified in dystrophin gene in developing countries

DMD gene which is composed of 79 exons is the largest known gene located on X chromosome (Xp21). Point mutations in the dystrophin gene are responsible for 30–35% of cases with DMD/BMD. Mutation analysis of all the exons of the DMD gene is costly in developing countries, therefore, a few of the exons are selected to be analyzed routinely in clinical laboratories. In this study, direct sequencing was used for detection of point mutations in 10 exons of dystrophin gene in patients affected with DMD without detectable large rearrangements. Freely available programs were used to predict the damaging effects of the mutations. Point mutations were successfully detected in three patients. Three novel mutations, two missense mutations located on nonconservative domains and a single nucleotide deletion, were detected. Missense mutations were predicted to change splicing efficiency. Detection of point mutations by DNA analysis followed by prediction of the pathogenecity by using bioinformatic tool might be an asset to provide proper diagnosis or genetic counseling to patients and their family.     

Does superparasitism improve host suitability for parasitoid development? A case study in the Microplitis rufiventris-Spodoptera littoralis system

Superparasitism refers to the oviposition behavior of parasitoid females who lay their eggs in an already parasitized host. Recent studies have shown that allocation of additional eggs to an already parasitized host may be beneficial under certain conditions. In the present work, mortality of Microplitis rufiventris wasps was significantly influenced by both host instar of Spodoptera littoralis larvae at parasitism and level of parasitism. In single parasitization, all host instars (first through sixth) were not equally suitable. Percentage of emergence success of wasp larvae was very high in parasitized first through third (highly suitable hosts), fell to 60% in the fourth instar (moderate suitable) and sharply decreased in the penultimate (5th) instars (marginally suitable). Singly parasitized sixth (last) instar hosts produced no wasp larvae (entirely unsuitable), pupated and eclosed to apparently normal adult moths. The scenario was different under superparasitism, whereas supernumerary individuals in the highly suitable hosts were almost always killed as first instars, superparasitization in unsuitable hosts (4th through 6th) had significant increase in number of emergence success of wasp larvae. Also, significantly greater number of parasitoid larvae successfully developed in unsuitable hosts containing three wasp eggs than counterparts containing two wasp eggs. Moreover, the development of surplus wasp larvae was siblicidal in earlier instars and nonsiblicidal gregarious one in the penultimate and last “sixth” instars. It is suggested that the optimal way for M. rufiventris to deal with high quality hosts (early instars) is to lay a single egg, while the optimal way to deal with low quality hosts (late instars) might be to superparasitize these hosts.     

Tetramethylpyrazine Ameliorates Rotenone-Induced Parkinson’s Disease in Rats: Involvement of Its Anti-Inflammatory and Anti-Apoptotic Actions

Parkinson’s disease (PD) is a slowly progressive neurodegenerative movement disorder. Apoptosis, neuroinflammation, and oxidative stress are the current hypothesized mechanisms for PD pathogenesis. Tetramethylpyrazine (TMP), the major bioactive component of Ligusticum wallichii Franchat (ChuanXiong), Family Apiaceae, reportedly has anti-apoptotic, anti-inflammatory and antioxidant effects. This study investigated the role of ‘TMP’ in preventing rotenone-induced neurobiological and behavioral sequelae. A preliminary dose–response study was conducted where rats received TMP (10, 20, and 40 mg/kg, i.p.) concomitantly with rotenone (2 mg/kg, s.c.) for 4 weeks. Catalepsy, locomotor activity, striatal dopamine content, and tyrosine hydroxylase “TH” and α-synuclein immunoreactivity were evaluated. The selected TMP dose (20 mg/kg) was used for western blot analysis of Bax, Bcl2, and DJ-1, immunohistochemical detection of nuclear factor kappa B (NF-кB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and glial fibrillary acidic protein (GFAP) expression, in addition to biochemical analysis of caspase-3 activity, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) levels. Results showed that TMP (20 mg/kg) significantly improved midbrain and striatal TH expression and striatal dopamine content as well as the motor deficits, compared to rotenone-treated group. These results were correlated with reduction in caspase-3 activity and α-synuclein expression, along with improvement of midbrain and striatal Bax/Bcl2 ratio compared to rotenone-treated group. TMP also attenuated rotenone-induced upregulation of Nrf2/HO-1 pathway. Furthermore, TMP downregulated rotenone-induced neuroinflammation markers: NF-кB, iNOS, COX2, and GFAP expression in both the midbrain and striatum. Taken together, the current study suggests that TMP is entitled to, at least partially, preventing PD neurobiological and behavioral deficits by virtue of its anti-apoptotic, anti-inflammatory, and antioxidant actions.     

Modified operative technique for involutional lower lid entropion

The paper presents a modified operative technique for involutional lower lid entropion. The prospective noncomparative study of 101 lower eyelids of 88 patients undergoing surgery for involutional lower lid entropion was conducted in period from September 2005 until March 2012. Indication for the surgery was entropion, previously untreated, with moderate to severe horizontal lid laxity and no clinically relevant medial and lateral canthal tendon laxity. The operative technique is our modification of Quickert and Jones procedures. Photo was taken preoperatively and one month after surgery. Clinical follow-up was at 7th postoperative day, one month and six months after surgery and in case of the recurrence. Long-term follow-up was obtained via telephone interviews. There were 44 male (50%) and 44 female (50%) patients included in the study. The age of patients was in average 73.27 +/- 8.1 years (range 53-90 years). Early postoperative complication was localized lid swelling found in two patients starting 4-6 weeks postoperatively at the area of absorbable suture. It resolved spontaneously in two and three weeks respectively. There was recurrence of entropion in 11 eyelids (10.89%) of 10 patients. The mean interval between primary surgery and the recurrence was 17.45 +/- 14.84 months (range 4-48 months). In these eyelids Jones procedure was performed. However in four eyelids of four patients from the recurrent group an additional surgery needed to be performed after 6, 12, 12 and 17 months respectively. Our modification of surgical treatment for involutional lower lid entropion was effective in 89.11% of eyelids. Complications of the procedure were scarce.     

Repigmentation in vitiligo: position paper of the Vitiligo Global Issues Consensus Conference

The Vitiligo Global Issues Consensus Conference (VGICC), through an international e‐Delphi consensus, concluded that ‘repigmentation’ and ‘maintenance of gained repigmentation’ are essential core outcome measures in future vitiligo trials. This VGICC position paper addresses these core topics in two sections and includes an atlas depicting vitiligo repigmentation patterns and color match. The first section delineates mechanisms and characteristics of vitiligo repigmentation, and the second section summarizes the outcomes of international meeting discussions and two e‐surveys on vitiligo repigmentation, which had been carried out over 3 yr. Treatment is defined as successful if repigmentation exceeds 80% and at least 80% of the gained repigmentation is maintained for over 6 months. No agreement was found on the best outcome measure for assessing target or global repigmentation, therefore highlighting the limitations of e‐surveys in addressing clinical measurements. Until there is a clear consensus, existing tools should be selected according to the specific needs of each study. A workshop will be conducted to address the remaining issues so as to achieve a consensus.