A pilot study of evaluation of semi-rigid and flexible catheters for less invasive surfactant administration in preterm infants with respiratory distress syndrome-a randomized controlled trial.

BACKGROUND: In respiratory distress syndrome, many neonatology centers worldwide perform minimal invasive surfactant application in premature infants, using small-diameter catheters for endotracheal intubation and surfactant administration. METHODS: In this single-center, open-label, randomized-controlled trial, preterm infants requiring surfactant administration after birth, using a standardized minimal invasive protocol, were randomized to two different modes of endotracheal catheterization: Flexible charrière-4 feeding tube inserted using Magill forceps (group 1) and semi-rigid catheter (group 2). Primary outcome was duration of laryngoscopy. Secondary outcomes were complication rate (intraventricular hemorrhage, soft-tissue damage in first week of life) and vital parameters during laryngoscopy. Between 2019 and 2020, 31 infants were included in the study. Prior to in-vivo testing, laryngoscopy durations were studied on a neonatal airway mannequin in students, nurses and doctors. RESULTS: Mean gestational age and birth weight were 27 + 6/7 weeks and 1009 g; and 28 + 0/7 weeks and 1127 g for group 1 and 2, respectively. Length of laryngoscopy was similar in both groups (61.1 s and 64.9 s) overall (p.77) and adjusted for weight (p.70) or gestational age (p.95). Laryngoscopy failed seven times in group 1 (43.8%) and four times (26.7%) in group 2 (p.46). Longer laryngoscopy was associated with lower oxygen saturation with lowest levels occurring after failed laryngoscopy attempts. Secondary outcomes were similar in both groups. In vitro data on 40 students, 40 nurses and 12 neonatologists showed significant faster laryngoscopy in students and nurses group 2 (p < .0001) unlike in neonatologists (p.13). CONCLUSION: This study showed no difference in laryngoscopy duration in endotracheal catheterization when comparing semi-rigid and flexible catheters for minimal invasive surfactant application in preterm infants. In accordance with preliminary data and in contrast to published in-vitro trials, experienced neonatologists were able to perform endotracheal catheterization using both semi-rigid and flexible catheters at similar rates and ease, in vitro and in vivo. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05024435 Registered 27 August 2021-Retrospectively registered.

Introduction and feeding practices of solid food in preterm infants born in Salzburg!

BACKGROUND: It is shown that meeting the increased nutritional demand of preterm infants from birth is not only important for survival but essentially contributes to the infants` overall development and long-term health. While there are established guidelines for weaning term infants, evidence regarding preterm infants is scarce and less precise. The aim of this study was to identify the current practices on introducing solids to preterm infants amongst caregivers in Salzburg and determine potential reasons for early weaning. METHODS: Altogether 68 infants born between 24 0/7 and 36 6/7 weeks were recruited and detailed structured interviews with the caregivers were conducted at 17 weeks corrected age. Weight, height and head circumference were collected. RESULTS: 52% of the study group received solids before the recommended 17 weeks corrected age. For this group the mean age being 13.77 ± 1.11 weeks corrected age. Premature introduction of solids significantly correlates with exclusively and early formula-feeding. 34% were weaned due to recommendation by their paediatrician. 23% of the preterm infants even received solids before 12 weeks corrected age, putting them at risks for developing obesity, celiac disease and diabetes. CONCLUSIONS: This study shows the necessity for clear guidelines regarding the introduction of complementary feeding in preterm infants as well as the importance of their implementation. Caregivers should receive information on this topic early enough and they should fully understand the difference between chronological and corrected age.

Vedolizumab use after failure of TNF-α antagonists in children and adolescents with inflammatory bowel disease.

BACKGROUND: Vedolizumab is safe and effective in adult patients with Crohn's disease (CD) and ulcerative colitis (UC); however, data in children with inflammatory bowel disease (IBD) are scarce. Therefore, we evaluated vedolizumab use in a cohort of Austrian paediatric patients with IBD. METHODS: Twelve patients (7 female; 7 CD; 5 UC), aged 8-17 years (median, 15 years), with severe IBD who received vedolizumab after tumour necrosis factor α antagonist treatment were retrospectively analysed. Clinical activity scores, relevant laboratory parameters, and auxological measures were obtained at infusion visits. RESULTS: In the CD group, 1/7 patient discontinued therapy due to a severe systemic allergic reaction; 1/7 and 2/7 patients achieved complete and partial response, respectively, at week 14; and 3/7 patients discontinued therapy due to a primary non-response or loss of response. In the UC group, complete clinical remission was achieved at weeks 2, 6, and 14 in 2/5, 1/5 and 1/5 patients respectively; partial response was observed in one patient at week 2. CD activity scores did not significantly change from baseline to week 38 (median 47.5 vs. 40 points, p = 1,0), while median UC activity scores changed from 70 to 5 points (p < 0,001). Substantial weight gain and increased albumin and haemoglobin levels were observed in both groups. CONCLUSION: These results demonstrate that vedolizumab can be an effective treatment for individual paediatric patients with IBD who are unresponsive, intolerant, or experience a loss of efficacy in other therapies. However, vedolizumab appears to be more effective in paediatric UC than in paediatric CD.

Single Point Insulin Sensitivity Estimator in Pediatric Non-Alcoholic Fatty Liver Disease.

Background: Attenuated insulin-sensitivity (IS) is a central feature of pediatric non-alcoholic fatty liver disease (NAFLD). We recently developed a new index, single point insulin sensitivity estimator (SPISE), based on triglycerides, high-density-lipoprotein and body-mass-index (BMI), and validated by euglycemic-hyperinsulinemic clamp-test (EHCT) in adolescents. This study aims to assess the performance of SPISE as an estimation of hepatic insulin (in-)sensitivity. Our results introduce SPISE as a novel and inexpensive index of hepatic insulin resistance, superior to established indices in children and adolescents with obesity. Materials and Methods: Ninety-nine pubertal subjects with obesity (13.5 ± 2.0 years, 59.6% males, overall mean BMI-SDS + 2.8 ± 0.6) were stratified by MRI (magnetic resonance imaging) into a NAFLD (>5% liver-fat-content; male n=41, female n=16) and non-NAFLD (≤5%; male n=18, female n=24) group. Obesity was defined according to WHO criteria (> 2 BMI-SDS). EHCT were used to determine IS in a subgroup (n=17). Receiver-operating-characteristic (ROC)-curve was performed for diagnostic ability of SPISE, HOMA-IR (homeostatic model assessment for insulin resistance), and HIRI (hepatic insulin resistance index), assuming null hypothesis of no difference in area-under-the-curve (AUC) at 0.5. Results: SPISE was lower in NAFLD (male: 4.8 ± 1.2, female: 4.5 ± 1.1) than in non-NAFLD group (male 6.0 ± 1.6, female 5.6 ± 1.5; P< 0.05 {95% confidence interval [CI]: male NAFLD 4.5, 5.2; male non-NAFLD 5.2, 6.8; female NAFLD 4.0, 5.1, female non-NAFLD 5.0, 6.2}). In males, ROC-AUC was 0.71 for SPISE (P=0.006, 95% CI: 0.54, 0.87), 0.68 for HOMA-IR (P=0.038, 95% CI: 0.48, 0.88), and 0.50 for HIRI (P=0.543, 95% CI: 0.27, 0.74). In females, ROC-AUC was 0.74 for SPISE (P=0.006), 0.59 for HOMA-IR (P=0.214), and 0.68 for HIRI (P=0.072). The optimal cutoff-level for SPISE between NAFLD and non-NAFLD patients was 5.18 overall (Youden-index: 0.35; sensitivity 0.68%, specificity 0.67%). Conclusion: SPISE is significantly lower in juvenile patients with obesity-associated NAFLD. Our results suggest that SPISE indicates hepatic IR in pediatric NAFLD patients with sensitivity and specificity superior to established indices of hepatic IR.

Expression of Oxidative Phosphorylation Complexes and Mitochondrial Mass in Pediatric and Adult Inflammatory Bowel Disease.

INTRODUCTION: Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a multifactorial intestinal disorder but its precise etiology remains elusive. As the cells of the intestinal mucosa have high energy demands, mitochondria may play a role in IBD pathogenesis. The present study is aimed at evaluating the expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes in IBD. Material and Methods. 286 intestinal biopsy samples from the terminal ileum, ascending colon, and rectum from 124 probands (34 CD, 33 UC, and 57 controls) were stained immunohistochemically for all five OXPHOS complexes and the voltage-dependent anion-selective channel 1 protein (VDAC1 or porin). Expression levels were compared in multivariate models including disease stage (CD and UC compared to controls) and age (pediatric/adult). RESULTS: Analysis of the terminal ileum of CD patients revealed a significant reduction of complex II compared to controls, and a trend to lower levels was evident for VDAC1 and the other OXPHOS complexes except complex III. A similar pattern was found in the rectum of UC patients: VDAC1, complex I, complex II, and complex IV were all significantly reduced, and complex III and V showed a trend to lower levels. Reductions were more prominent in older patients compared to pediatric patients and more marked in UC than CD. CONCLUSION: A reduced mitochondrial mass is present in UC and CD compared to controls. This is potentially a result of alterations of mitochondrial biogenesis or mitophagy. Reductions were more pronounced in older patients compared to pediatric patients, and more prominent in UC than CD. Complex I and II are more severely compromised than the other OXPHOS complexes. This has potential therapeutic implications, since treatments boosting biogenesis or influencing mitophagy could be beneficial for IBD treatment. Additionally, substances specifically stimulating complex I activity should be tested in IBD treatment.

Determinants of hyperglucagonemia in pediatric non-alcoholic fatty liver disease.

Objective: Over the years, non-alcoholic fatty liver (NAFLD) disease has progressed to become the most frequent chronic liver disease in children and adolescents. The full pathology is not yet known, but disease progression leads to cirrhosis and hepatocellular carcinoma. Risk factors included hypercaloric diet, obesity, insulin resistance and genetics. Hyperglucagonemia appears to be a pathophysiological consequence of hepatic steatosis, thus, the hypothesis of the study is that hepatic fat accumulation leads to increased insulin resistance and impaired glucagon metabolism leading to hyperglucagonemia in pediatric NAFLD. Methods: 132 children and adolescents between 10 and 18 years, with varying degrees of obesity, were included in the study. Using Magnetic Resonance Imaging (MRI) average liver fat was determined, and patients were stratified as NAFLD (>5% liver fat content) and non-NAFLD (<5%). All patients underwent a standardized oral glucose tolerance test (OGTT). Additionally, anthropometric parameters (height, weight, BMI, waist circumference, hip circumference) such as lab data including lipid profile (triglycerides, HDL, LDL), liver function parameters (ALT, AST), uric acid, glucose metabolism (fasting insulin and glucagon, HbA1c, glucose 120 min) and indices evaluating insulin resistance (HIRI, SPISE, HOMA-IR, WBISI) were measured. Results: Children and adolescents with NAFLD had significantly higher fasting glucagon values compared to the non-NAFLD cohort (p=0.0079). In the NAFLD cohort univariate analysis of fasting glucagon was associated with BMI-SDS (p<0.01), visceral adipose tissue volume (VAT) (p<0.001), average liver fat content (p<0.001), fasting insulin concentration (p<0.001), triglycerides (p<0.001) and HDL (p=0.034). This correlation equally applied to all insulin indices HOMA-IR, WBISI, HIRI (all p<0.001) and SPISE (p<0.002). Multivariate analysis (R² adjusted 0.509) for the same subgroup identified HIRI (p=0.003) and VAT volume (p=0.017) as the best predictors for hyperglucagonemia. Average liver fat content is predictive in pediatric overweight and obesity but not NAFLD. Conclusions: Children and adolescents with NAFLD have significantly higher fasting plasma glucagon values, which were best predicted by hepatic insulin resistance and visceral adipose tissue, but not average liver fat content.

The Psychological and Biological Impact of "In-Person" vs. "Virtual" Choir Singing in Children and Adolescents: A Pilot Study Before and After the Acute Phase of the COVID-19 Outbreak in Austria.

Psychobiological responses to music have been examined previously in various naturalistic settings in adults. Choir singing seems to be associated with positive psychobiological outcomes in adults. However, evidence on the effectiveness of singing in children and adolescents is sparse. The COVID-19 outbreak is significantly affecting society now and in the future, including how individuals engage with music. The COVID-19 pandemic is occurring at a time when virtual participation in musical experiences such as singing in a virtual choir has become more prevalent. However, it remains unclear whether virtual singing leads to different responses in comparison with in-person singing. We evaluated the psychobiological effects of in-person choral singing (7 weeks, from January to March 2020, before the COVID-19 outbreak) in comparison with the effects of virtual choral singing (7 weeks, from May to July 2020, after schools partly re-opened in Austria) in a naturalistic pilot within-subject study. A group of children and young adolescents (N = 5, age range 10-13, female = 2) from a school in Salzburg, Austria were recruited to take part in the study. Subjective measures (momentary mood, stress) were taken pre- and post-singing sessions once a week. Additionally, salivary biomarkers (cortisol and alpha-amylase) and quantity of social contacts were assessed pre- and post-singing sessions every second week. Psychological stability, self-esteem, emotional competences, and chronic stress levels were measured at the beginning of in-person singing as well as at the beginning and the end of the virtual singing. We observed a positive impact on mood after both in-person and virtual singing. Over time, in-person singing showed a pre-post decrease in salivary cortisol, while virtual singing showed a moderate increase. Moreover, a greater reduction in stress, positive change in calmness, and higher values of social contacts could be observed for the in-person setting compared to the virtual one. In addition, we observed positive changes in psychological stability, maladaptive emotional competences, chronic stress levels, hair cortisol, self-contingency and quality of life. Our preliminary findings suggest that group singing may provide benefits for children and adolescents. In-person singing in particular seems to have a stronger psychobiological effect.

Changes in the expression of oxidative phosphorylation complexes in the aging intestinal mucosa.

OBJECTIVE: Mitochondria produce cellular energy via oxidative phosphorylation (OXPHOS), mediated by respiratory chain complexes I to IV and ATP synthase (complex V). Mitochondrial respiratory complexes have been shown to decline with age in several tissues. As the intestinal epithelium is a tissue with a high energy demand, the aim of the present study was to establish whether the expression profile of OXPHOS subunits in the intestinal mucosa changes during the aging process. DESIGN: Biopsies of intestinal mucosa with no evidence of endoscopic or histomorphologic abnormalities, taken from 55 patients (mean age 42 years, age range 4-82 years; 62% female), were divided into four age groups (4-19, 20-39, 40-59, ≥60 years). Sections from different intestinal segments (terminal ileum, ascending colon, and sigmoid colon/rectum) were stained immunohistochemically (IHC) for subunits of OXPHOS complexes I-V and the voltage-dependent anion-selective channel 1 protein (VDAC1, porin), a marker of mitochondrial mass. Scores for IHC staining were determined by multiplication of the staining intensity and the percentage of positive cells. In addition, the numbers of intestinal crypts staining positive, partly positive, and negative were assessed. RESULTS: The average protein expression levels of OXPHOS subunits increased continuously from childhood onward, peaked in persons aged 20 to 59 years, and declined thereafter. This was seen for complexes II to V in the terminal ileum, complexes I to V in the ascending colon, and complexes I to IV in the sigmoid colon/rectum. Across all age groups, no effect of age on expression of the porin subunit VDAC1 was detected. The number of complex I- and IV-negative crypts in different intestinal segments increased with age. CONCLUSION: The protein expression levels of OXPHOS complexes increases from childhood onward and declines in elderly individuals, while the numbers of crypts with partial or complete loss of expression of complexes I and IV increase continuously with age. These data suggest that the continued reductions in the levels of mitochondrial OXPHOS complexes in crypts might be compensated in adulthood, but that, ultimately, reduced expression levels occur in persons aged 60 years and older. These findings raise two important questions: first, can the process of aging could be delayed through (pharmacological) intervention of mitochondrial pathways, and second, pathophysiologically, are these findings associated with disorders of the intestinal mucosa, e.g. inflammation?

Serum Ferritin Correlates With Liver Fat in Male Adolescents With Obesity.

Non-alcoholic fatty liver disease (NAFLD) contributes essentially to the burden of obesity and can start in childhood. NAFLD can progress to cirrhosis and hepatocellular carcinoma. The early phase of NAFLD is crucial because during this time the disease is fully reversible. Pediatric NAFLD shows unique features of histology and pathophysiology compared to adults. Changes in serum iron parameters are common in adult NAFLD and have been termed dysmetabolic iron overload syndrome characterized by increased serum ferritin levels and normal transferrin saturation; however, the associations of serum ferritin, inflammation, and liver fat content have been incompletely investigated in children. As magnetic resonance imaging (MRI) is an excellent measure for the degree of liver steatosis, we applied this method herein to clarify the interaction between ferritin and fatty liver in male adolescents. For this study, one hundred fifty male pediatric patients with obesity and who are overweight were included. We studied a subgroup of male patients with (n = 44) and without (n = 18) NAFLD in whom we determined liver fat content, visceral adipose tissue, and subcutaneous adipose tissue extent with a 1.5T MRI (Philips NL). All patients underwent a standardized oral glucose tolerance test. We measured uric acid, triglycerides, HDL-, LDL-, total cholesterol, liver transaminases, high sensitive CRP (hsCRP), interleukin-6, HbA1c, and insulin. In univariate analysis, ferritin was associated with MRI liver fat, visceral adipose tissue content, hsCRP, AST, ALT, and GGT, while transferrin and soluble transferrin receptor were not associated with ferritin. Multivariate analysis identified hsCRP and liver fat content as independent predictors of serum ferritin in the pediatric male patients. Our data indicate that serum ferritin in male adolescents with obesity is mainly determined by liver fat content and inflammation but not by body iron status.

Consejos para escribir un artículo científico. Parte 1: la práctica de la escritura / Tips for Writing a Scientific Paper: The Practice of Writing

La escritura de artículos académicos es una competencia necesaria para la difusión del conocimiento científico y para el desarrollo profesional de quienes trabajan en diversas disciplinas. Sin embargo, a pesar de su importancia, esta habilidad compleja no suele ser enseñada en forma sistemática, lo que puede operar como una barrera para que los investigadores comuniquen los resultados de sus trabajos. En esta primera entrega, sintetizamos los principales consejos que han brindado expertos en la temática, añadiendo algunos de nuestra experiencia personal que consideramos útiles para facilitar el proceso de la escritura académica y el desarrollo de esta competencia en un contexto colaborativo. En una segunda entrega profundizaremos respecto de la problemática de la escritura de las diferentes secciones de un artículo científico y se ofrecerán consejos para optimizarla y volverla lo más eficaz posible. (AU)

Academic writing is essential for scientific knowledge dissemination and the professional development of those working in various disciplines. Yet, however important this complex skill is, it is not usually taught systematically, a fact that can act as a barrier for researchers to communicate the results of their work. In this first part, we synthesize the main tips provided by experts in the field, adding some of our personal experiences that they consider relevant to facilitate the process of academic writing and develop this skill in a collaborative context. In a second article, we will go deeper into the problem of writing the different sections of a scientific article and offer advice on ways to optimize it and make it as effective as possible. (AU)

The effect of local injection of botulinum toxin A on the immunoreactivity of nNOS in the rat submandibular gland: an immunohistochemical study.

PURPOSE: In our study, we intend to investigate the influence of local injections of botulinum toxin A on the activity of neuronal nitric oxide synthase (nNOS) in submandibular glands of adult rats. Since interest has been focused on the role of nitric oxide (NO) as a possible neuromodulator of secretory regulation processes in the upper aerodigestive tract, it was the aim of the present study to show that the toxin also interferes with the metabolic actions of NO on investigated rat submandibular glands. It is of great clinical interest whether the NO pathway is able to influence salivary gland secretion. Increasing of knowledge in this field maybe helpful to treat sialorrhoea, especially in juvenile otolaryngologic and neurologic patients. MATERIALS AND METHODS: We performed immunohistochemical reaction of neuronal nitric oxide synthase (nNOS) in the submandibular gland of female adult Wistar rats, both in native (untreated) glands and after intraglandular injection of botulinum toxin A under general anesthesia. The immunoreactivity of nNOS was investigated on different times after injection. RESULTS: Other than in the untreated glands, there was a significant decrease of nNOS in the treated organs, which became stronger with extended toxin exposure time. The present study shows explicit data on the effect of botulinum toxin A injection on a higher number of examined submandibular glands and is able to analyze a time course of the effect duration. CONCLUSION: In our study, it was shown that botulinum toxin A had an influence on the immunoreactivity of neuronal nitric oxide synthase (nNOS) in submandibular glands. Therefore, the participation of nitric oxide (NO) in the regulation of secretion from these organs seems to be evident. It might be assumed that the influence of botulinum toxin A on nNOS in the submandibular gland of the rat is able to explain the sometimes longer duration of toxin effect at the neuroglandular junction than at the motor endplate.

Uso de bifosfonatos en pacientes con osteopenia / Biphosphonates in patients with osteopenia

La osteopenia, una disminución de la densidad mineral ósea de menor severidad que la osteoporosis, definida por valores de T-score entre -1,0 y -2,5 en la densitometría ósea , podría asociarse con un mayor riesgo de fracturas. Motivado por el pedido de una paciente con osteopenia que solicita a su médico algún medicamento que le ayude a disminuir su riesgo de fracturas, el autor se pregunta si los bifosfonatos podrían ser beneficiosos para las pacientes con este factor de riesgo. Luego de realizar una búsqueda bibliográfica y seleccionar la evidencia más reciente y de mejor calidad, se concluye que estos fármacos podrían ser útiles para prevenir fracturas en mujeres mayores de 65 años con elevado riesgo de fractura,independientemente del resultado de la densitometría. (AU)

Osteopenia, a minor decrease in bone mineral density, defined by T-score values between -1.0 and -2.5 in a bone densitometry, is associated with an increased risk of fractures. Moved by the request of a patient with osteopenia who asks her doctor for any medication that may help her reduce his risk of fractures, the author wonders if bisphosphonates could be beneficial for patients with this condition. After conducting a bibliographic search and selecting the most recent and best quality evidence, he concluded that these drugs could be useful to prevent fractures in women older than 65 years with ahigh risk of fracture, regardless of densitometry results. (AU)

Uso de pregabalina en el tratamiento de la lumbociatalgia / Pregabalin for treatment of low back pain

La lumbociatalgia es un problema clínico común, que en la mayoría de los casos se autolimita y se puede tratar en forma conservadora, usando medidas no farmacológicas y analgésicos como paracetamol o los antiinflamatorios no esteroi-deos. Otro medicamento muy utilizado en nuestro medio es la pregabalina, a pesar de que no se encuentra aprobada para dicha indicación. En este trabajo, el autor se pregunta acerca de la utilidad clínica de la pregabalina y luego de hacer una búsqueda bibliográfica sobre la evidencia más actualizada y de mejor calidad acerca del tema, concluye que no es efectiva para lumbociatalgia y que se acompaña de efectos adversos significativos. Esto coincide con las recomenda-ciones de las guías internacionales, que en su mayoría desaconsejan el uso de anticonvulsivantes para la lumbalgia. (AU)

Sciatica is a common clinical situation, in most cases self-limited and which can be managed conservatively with nonpharmaco-logic treatment and analgesics, such as paracetamol or nonsteroidal anti-inflammatory drugs. Pregabalin is also commonly used, despite not being approved for this indication. In this article, the author queries about the clinical usefulness of pregabalin, and after carrying out a bibliographic search of the most recent and best-quality evidence, concludes that it is not effective in sciatica while it causes significant adverse effects. This is in line with the recommendations of most international guidelines,that do not recommend the use of anticonvulsivants drugs for the treatment of lumbalgia. (AU)

Immunohistochemical investigations of the influence of botulinum toxin A on the immunoreactivity of nNOS in the parotid gland of the rat.

PURPOSE: We wanted to prove the hypothesis that local injections of botulinum toxin A have an influence on the immunoreactivity of neuronal nitric oxide synthase (nNOS) in parotid glands of adult rats. MATERIALS AND METHODS: Our group carried out immunohistochemical reaction of neuronal nitric oxide synthase (nNOS) in the parotid gland of female adult Wistar rats, in native (untreated) glands and after intraglandular injection of botulinum toxin A under general anesthesia. The immunoreactivity of nNOS was investigated on different times after injection. RESULTS: Compared with the untreated glands, there was a significant decrease of nNOS in the treated organs that became stronger with extended toxin exposure time. After our laboratory in a pilot study had already shown in general a decrease of nNOS immunoreactivity after injection of botulinum toxin A into the cephalic salivary glands of the rat, the present study shows more explicit data on the effect of botulinum toxin A injection on a higher number of examined parotid glands and analyzes a time course of the effect duration. CONCLUSIONS: In our study, it was shown that botulinum toxin A had an influence on the immunoreactivity of neuronal nitric oxide synthase (nNOS) in parotid glands. Participation of nitric oxide (NO) in the regulation of secretion from the parotid gland of the rat seems to be likely. It might be assumed that the influence of botulinum toxin A on nNOS in the parotid gland of the rat is able to explain the sometimes longer duration of toxin effect at the neuroglandular junction than at the motor endplate.

Immunohistochemical evidence of nNOS and changes after intraglandular application of botulinum toxin A in cephalic salivary glands of adult rats.

The purpose of our study was to investigate the possible influence of local injections of botulinum toxin A on the activity of neuronal nitric oxide synthase (nNOS) in cephalic salivary glands of adult rats. The role of nitric oxide (NO) as a possible neuromodulator of vascular regulation and in particular regulation of secretion in the upper respiratory and aerodigestive tract is discussed. We present immunohistochemical evidence of nNOS in the salivary glands of female adult Wistar rats, both in native (untreated) glands and after intraglandular injection of botulinum toxin A under general anesthesia. Other than in the untreated glands, there was a significant decrease in nNOS in the treated organs which became stronger with extended toxin exposure time. After our laboratory had already shown a decrease in acetylcholinesterase immunoreactivity after injection of botulinum toxin A into the cephalic salivary glands of the rat, the present study discusses a possible participation of NO in the regulation of secretion from these organs. As a conclusion, it might be assumed that the influence of botulinum toxin A on nNOS in the cephalic salivary glands of the rat is able to explain the sometimes longer duration of the toxin effect at the neuroglandular junction than at the motor endplate.