Repair of Oronasal Fistulae by Interposition of Multilayered Amniotic Membrane Allograft

Background: Oronasal fistulas are a frequent complication after cleft palate surgery. Numerous repair methods have been described, but wound-healing problems occur often. The authors investigated, for the first time, the suitability of multilayered amniotic membrane allograft for fistula repair in a laboratory experiment (part A), a swine model (part B), and an initial patient series (part C). Methods: In part A, one-, two-, and four-layer porcine and human amniotic membranes (n = 20 each) were fixed in a digital towing device and the force needed for rupture was determined. In part B, iatrogenic oronasal fistulas in 18 piglets were repaired with amniotic membrane allograft, autofetal amniotic membrane, or small intestinal submucosa (n = 6 each). Healing was evaluated by probing and visual inflammation control (no/moderate/strong) on postoperative days 3, 7, 10, and 76. Histological analysis was performed to visualize tissue architecture. In part C, four patients (two women and two men, ages 21 to 51 years) were treated with multilayered amniotic membrane allograft. Results: In part A, forces needed for amniotic membrane rupture increased with additional layers (p < 0.001). Human amniotic membrane was stronger than porcine membrane (p < 0.001). In part B, fistula closure succeeded in all animals treated with amniotic membrane with less inflammation than in the small intestinal submucosa group. One fistula remained persistent in the small intestinal submucosa group. In part C, all fistulas healed completely without inflammation. Conclusions: Amniotic membrane is an easily available biomaterial and can be used successfully for oronasal fistula repair. The multilayer technique and protective plates should be utilized to prevent membrane ruptures

Sympathomimetic effects of chronic methamphetamine abuse on oral health: a cross-sectional study

Background: Methamphetamine, a highly addictive sympathomimetic stimulant, is currently widely abused worldwide and has been associated with devastating effects on oral health, resulting in the term "meth mouth". However, "meth mouth" pathology is primarily based on case reports with a lack of systematic clinical evaluation. Therefore, we have conducted a systematic study to investigate (1) the pharmacological impact of methamphetamine on oral health with regard to saliva function, including the parameters saliva flow rate and total saliva production (ml/5 min) and the buffering capacity of saliva;(2) the contribution of the symptoms of bruxism and muscle trismus to potential oral health damage. Methods: We assessed the data of 100 chronic methamphetamine abusers and 100 matched-pair comparison participants. Primarily, we conducted an anamnesis with all methamphetamine abusers with regard to saliva dysfunctions, jaw clenching and pain in the temporomandibular joint. Subsequently, in the first part of the clinical enquiry, we tested the saliva flow rate and the total saliva production (ml/5 min) by using the sialometry method and the buffer capacity of saliva by determining the pH-value. In the second part of the clinical enquiry, we evaluated bruxism symptoms with respect to generalized tooth attrition, dentine exposure and visible enamel cracks and examined a potential muscle trismus by measuring the maximal opening of the mouth. Results: The majority of methamphetamine abusers reported a dry mouth (72 %) and jaw clenching (68 %). Almost half of all methamphetamine abusers experienced pain in the temporomandibular joint (47 %). With regard to the clinical findings, methamphetamine abusers showed significantly lower total saliva production (ml/5 min) (p 0.05). Conclusions: The sympathomimetic effects of chronic methamphetamine abuse may lead to dry mouth and extensive bruxism and therefore can increase the risk for caries decay, periodontal lesions and tooth wear. Furthermore, a significant decline of saliva buffer capacity in methamphetamine abusers may trigger the risk for dental erosions. Methamphetamine abusers and practitioners should be aware of these symptoms

A common molecular mechanism for cognitive deficits and craving in alcoholism

Alcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. The medial prefrontal cortex, a key brain region for executive control, is prone to alcohol-induced neuroadaptations. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood. Here using a bi-directional neuromodulation approach we demonstrate a causal link for reduced prefrontal mGluR2 function and both impaired executive control and alcohol craving. By neuron-specific prefrontal knockdown of mGluR2 in rats, we generated a phenotype of reduced cognitive flexibility and excessive alcohol-seeking. Conversely, restoring prefrontal mGluR2 levels in alcohol-dependent rats rescued these pathological behaviors. Also targeting mGluR2 pharmacologically reduced relapse behavior. Finally, we developed a FDG-PET biomarker to identify those individuals that respond to mGluR2-based interventions. In conclusion, we identified a common molecular pathological mechanism for both executive dysfunction and alcohol craving, and provide a personalized mGluR2-mechanism-based intervention strategy for medication development of alcoholism

Repair of Oronasal Fistulae by Interposition of Multilayered Amniotic Membrane Allograft

Background: Oronasal fistulas are a frequent complication after cleft palate surgery. Numerous repair methods have been described, but wound-healing problems occur often. The authors investigated, for the first time, the suitability of multilayered amniotic membrane allograft for fistula repair in a laboratory experiment (part A), a swine model (part B), and an initial patient series (part C). Methods: In part A, one-, two-, and four-layer porcine and human amniotic membranes (n = 20 each) were fixed in a digital towing device and the force needed for rupture was determined. In part B, iatrogenic oronasal fistulas in 18 piglets were repaired with amniotic membrane allograft, autofetal amniotic membrane, or small intestinal submucosa (n = 6 each). Healing was evaluated by probing and visual inflammation control (no/moderate/strong) on postoperative days 3, 7, 10, and 76. Histological analysis was performed to visualize tissue architecture. In part C, four patients (two women and two men, ages 21 to 51 years) were treated with multilayered amniotic membrane allograft. Results: In part A, forces needed for amniotic membrane rupture increased with additional layers (p < 0.001). Human amniotic membrane was stronger than porcine membrane (p < 0.001). In part B, fistula closure succeeded in all animals treated with amniotic membrane with less inflammation than in the small intestinal submucosa group. One fistula remained persistent in the small intestinal submucosa group. In part C, all fistulas healed completely without inflammation. Conclusions: Amniotic membrane is an easily available biomaterial and can be used successfully for oronasal fistula repair. The multilayer technique and protective plates should be utilized to prevent membrane ruptures

Immunolocalization of antimicrobial and cytoskeletal components in the serous glands of human sinonasal mucosa

Secretory cells in the seromucous glands of paranasal sinuses secrete antibacterial proteins for innate immune mucosal integrity. We studied the localization of antimicrobial and cytoskeletal components of the human seromucous glands and respiratory epithelium of the maxillary sinus and the ethmoidal cells by immunohistochemical methods. The presence of a variety of defense proteins such as lysozyme, lactoferrin, cathelicidin, and defensin-1, -2, -3 point to a crucial role in the immune defense for the respiratory tract. Cytoskeletal proteins such as actin, myosin 2, cytokeratin 7 and 19, α- and β-tubulin, investigated for the first time in glands of paranasal sinuses, showed a stronger expression at the apical and lateral cell membrane. The localization of the cytoskeletal proteins might point to their participation in exocrine secretory processes and stabilizing effects

Evaluation of Human Amniotic Membrane as a Wound Dressing for Split-Thickness Skin-Graft Donor Sites

Human amniotic membrane (HAM) has been used as a biomaterial in various surgical procedures and exceeds some qualities of common materials. We evaluated HAM as wound dressing for split-thickness skin-graft (STSG) donor sites in a swine model (Part A) and a clinical trial (Part B). Part A: STSG donor sites in 4 piglets were treated with HAM or a clinically used conventional polyurethane (PU) foil (n=8 each). Biopsies were taken on days 5, 7, 10, 20, 40, and 60 and investigated immunohistochemically for alpha-smooth muscle actin (αSMA: wound contraction marker), von Willebrand factor (vWF: angiogenesis), Ki-67 (cell proliferation), and laminin (basement membrane integrity). Part B: STSG donor sites in 45 adult patients (16 female/29 male) were treated with HAM covered by PU foam, solely by PU foam, or PU foil/paraffin gauze (n=15 each). Part A revealed no difference in the rate of wound closure between groups. HAM showed improved esthetic results and inhibitory effects on cicatrization. Angioneogenesis was reduced, and basement membrane formation was accelerated in HAM group. Part B: no difference in re-epithelialization/infection rate was found. HAM caused less ichor exudation and less pruritus. HAM has no relevant advantage over conventional dressings but might be a cost-effective alternative

Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism

Alcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood, and new effective pharmacological treatments are desired. Here, using a bidirectional neuromodulation approach, we demonstrate a causal link between reduced prefrontal mGluR2 function and both impaired executive control and alcohol craving. A neuron-specific prefrontal mGluR2 knockdown in rats generated a phenotype of reduced cognitive flexibility and excessive alcohol seeking. Conversely, virally restoring prefrontal mGluR2 levels in alcohol-dependent rats rescued these pathological behaviors. In the search for a pharmacological intervention with high translational potential, psilocybin was capable of restoring mGluR2 expression and reducing relapse behavior. Last, we propose a FDG-PET biomarker strategy to identify mGluR2 treatment-responsive individuals. In conclusion, we identified a common molecular pathological mechanism for both executive dysfunction and alcohol craving and provided a personalized mGluR2 mechanism-based intervention strategy for medication development for alcoholism