Crossed-beam and theoretical studies of multichannel nonadiabatic reactions: branching fractions and role of intersystem crossing for O(3P) + 1,3-butadiene.

Atomic oxygen reactions can contribute significantly to the oxidation of unsaturated aliphatic and aromatic hydrocarbons. The reaction mechanism is started by electrophilic O atom addition to the unsaturated bond(s) to form "chemically activated" triplet oxy-intermediate(s), which can evolve adiabatically on the triplet potential energy surface (PES) and nonadiabatically via intersystem crossing on the singlet PES, forming intermediates that undergo unimolecular decomposition to a variety of bimolecular product channels. Here, we apply a combined crossed molecular beam (CMB)-theoretical approach to the study of the O(3P) + 1,3-butadiene reaction. Although the kinetics of this reaction have been extensively investigated, little is known about the primary products and their branching fractions (BFs). In the present work, a total of eight product channels were observed and characterized in a CMB experiment at a collision energy of 32.6 kJ mol-1. Synergic ab initio transition-state theory-based master equation simulations coupled with nonadiabatic transition-state theory on coupled triplet/singlet PESs were employed to compute the product BFs and assist the interpretation of the CMB experimental results. The good agreement found between the theoretical predictions and CMB experiments supported the use of the adopted methodology for the prediction of channel-specific rate constants as a function of temperature and pressure suitable to be used for the kinetic modeling of 1,3-butadiene oxidation and of systems where 1,3-butadiene is an important intermediate.

H-Abstraction reactions by OH, HO2, O, O2 and benzyl radical addition to O2 and their implications for kinetic modelling of toluene oxidation.

Alkylated aromatics constitute a significant fraction of the components commonly found in commercial fuels. Toluene is typically considered as a reference fuel. Together with n-heptane and iso-octane, it allows for realistic emulations of the behavior of real fuels by the means of surrogate mixture formulations. Moreover, it is a key precursor for the formation of poly-aromatic hydrocarbons, which are of relevance to understanding soot growth and oxidation mechanisms. In this study the POLIMI kinetic model is first updated based on the literature and on recent kinetic modelling studies of toluene pyrolysis and oxidation. Then, important reaction pathways are investigated by means of high-level theoretical methods, thereby advancing the present knowledge on toluene oxidation. H-Abstraction reactions by OH, HO2, O and O2, and the reactivity on the multi well benzyl-oxygen (C6H5CH2 + O2) potential energy surface (PES) were investigated using electronic structure calculations, transition state theory in its conventional, variational, and variable reaction coordinate forms (VRC-TST), and master equation calculations. Exploration of the effect on POLIMI model performance of literature rate constants and of the present calculations provides valuable guidelines for implementation of the new rate parameters in existing toluene kinetic models.

Efficacy of an emollient dermoprotective cream in the treatment of elderly skin affected by xerosis.

AIM: Xerosis cutis is a frequent condition in the elderly and the topical treatments are aimed to maintain a balance between the physiological components of the epidermis and an optimal moisturization. The aim was to evaluate the efficacy of a dermoprotective cream, glycerol and paraffin-based, in the treatment of individuals affected by senile xerosis. METHODS: The patients were recruited at the Professional Dermatology and Allergology Outpatient Clinic of the San Gallicano Dermatological Institute of Rome, between 1st January 2013 and 30th September 2014. To assess the efficacy of the cream, two different areas of treatment were identified in each patient upper the limbs. All patients were staged at baseline (T0) and evaluated after 14 days (T1) and 28 days (T2) of topical treatment, using five clinical parameters: scaling, sensation of skin tightness, presence of fissuring and excoriations from scratching and erythema. The itching degree was also evaluated using a 10-steps analogical scale. RESULTS: Fifty patients with xerosis, 25 with a severe and 25 with a moderate form, over 60 were recruited and evaluated. Median age was 65 years (IQR=61-70). After 28 day of topical administration of the cream, the 54.0% of patients showed the absence of signs of xerosis, the 44.0% a mild form and the 2.0% (one patient) a moderate form. Consistently, a progressive and significative reduction of itching and transepidermal water loss (TEWL), and an improvement in skin hydration was also measured. A good profile of tolerability and no episodes of undesirable side effects, was also observed. CONCLUSION: The topical daily use of a cream glycerol and paraffin-based, seem to able to control the xerosis in elderly patients, with a significant reduction of all associated signs and symptoms. Further additional data should be collected to better confirm the role of the topical treatment in the control of disease.

Immunologic biomarkers for clinical and therapeutic management of psoriasis.

BACKGROUND: The therapeutic management of psoriasis includes conventional treatments as well as the new generation of highly effective TNF-α inhibitors. However, psoriasis has proven to be a complex therapeutic challenge and treatment failures are not uncommon. Thus, laboratory biomarkers of disease progression/therapeutic efficacy may greatly help in the clinical management of psoriasis. AIMS: To identify laboratory biomarkers for clinical management and therapeutic monitoring of psoriasis. METHODS: An observational study performed on 59 patients, presenting moderate to severe psoriasis, undergoing treatment with anti-TNF-α agents (etanercept, adalimumab, and infliximab). Soluble and cellular immune/inflammatory parameters were assessed at baseline and after 12 and 24 weeks of treatment. RESULTS: Clinical efficacy was achieved in 88% of the subjects at 12 weeks, reaching 90% after 24 weeks. IL-6 and IL-22, which were elevated at baseline, were significantly reduced, in association with a significant decrease of CLA+ T cells and an increase of Treg lymphocytes. T, B, and NK cell subsets and T cell response to recall antigens did not show any evidence of immune suppression. CONCLUSIONS: Immune/inflammatory parameters including IL-6 and IL-22, CLA+ T cells, and Treg lymphocytes may prove to be valuable laboratory tools for the clinical and therapeutic monitoring of psoriasis.

Ultrastructural age-related changes in the sensory corpuscles of the human genital skin.

In human genital skin the majority of superficial sensory corpuscles is represented by glomerular corpuscles. These corpuscles show an own morphology. Our aim is to compare the ultra-structure of superficial sensory corpuscles in the penis skin of younger and older subjects. In this report the ultra-structure of the sensitive corpuscle in the penis skin of the younger and older subjects was compared, showing that the genital skin of the older humans contains more simple complexes than the younger ones. Our findings support the view that the age-related changes that can be observed in human glomerular genital corpuscles are consistent with an increase of the simple complexes and a strong decrease of the poly-lamellar one in the older people. These findings demonstrate that human genital corpuscles underwent age-related changes. Moreover our morphological findings can be correlated in relation to the clinical evolution of the sensitivity in the genital skin.

Cholinergic innervation of human mesenteric lymphatic vessels.

BACKGROUND: The cholinergic neurotransmission within the human mesenteric lymphatic vessels has been poorly studied. Therefore, our aim is to analyse the cholinergic nerve fibres of lymphatic vessels using the traditional enzymatic techniques of staining, plus the biochemical modifications of acetylcholinesterase (AChE) activity. MATERIALS AND METHODS: Specimens obtained from human mesenteric lymphatic vessels were subjected to the following experimental procedures: 1) drawing, cutting and staining of tissues; 2) staining of total nerve fibres; 3) enzymatic staining of cholinergic nerve fibres; 4) homogenisation of tissues; 5) biochemical amount of proteins; 6) biochemical amount of AChE activity; 6) quantitative analysis of images; 7) statistical analysis of data. RESULTS: The mesenteric lymphatic vessels show many AChE positive nerve fibres around their wall with an almost plexiform distribution. The incubation time was performed at 1 h (partial activity) and 6 h (total activity). Moreover, biochemical dosage of the same enzymatic activity confirms the results obtained with morphological methods. CONCLUSIONS: The homogenates of the studied tissues contain strong AChE activity. In our study, the lymphatic vessels appeared to contain few cholinergic nerve fibres. Therefore, it is expected that perivascular nerve stimulation stimulates cholinergic nerves innervating the mesenteric arteries to release the neurotransmitter AChE, which activates muscarinic or nicotinic receptors to modulate adrenergic neurotransmission. These results strongly suggest, that perivascular cholinergic nerves have little or no effect on the adrenergic nerve function in mesenteric arteries. The cholinergic nerves innervating mesenteric arteries do not mediate direct vascular responses.

Dopaminergic receptors in the human skin.

Dopamine is a neurotransmitter which plays an important role in many human organs including the skin. In this study we will examine the presence and the distribution of D1 and D2 dopamine receptors in a particular zone of the human skin. Samples of the human plantar skin were harvested during autopsies after the consent of relatives of the dead donors. In this study the following experimental procedures were performed: 1) drawing of the human plantar skin; 2) cutting of tissues; 3) staining of tissues; 4) staining of the nerve fibres; 5) radio-binding methods for labelling D1 and D2 dopamine receptors; 6) light microscope autoradiography; 7) quantitative analysis of images and 8) statistical analysis of data. The dopamine receptors D1 are distributed particularly in the dermis layer of the human plantar skin. They are numerous in lower epidermal layers (with exclusion of the corneal layer) and few in subcutaneous tissue. On the contrary D2 dopamine receptors are prominent in the subcutaneous tissue near the vessels. Quantitative analysis of images and statistical analysis of the data confirm all our results. The specific distribution of D1 and D2 dopamine receptors in the human plantar skin is in close relation with the functions of a particular zone of the human skin that supports the weight of all the body. Moreover the character of dopamine receptors distribution is very important for further understanding the role of these receptors in the human skin.

Density functional theory study of addition reactions of carbon-centered radicals to alkenes.

Addition reactions of carbon-centered radicals to unsaturated compounds have been studied using quantum chemistry. Following the review by Fischer and Radom (Angew. Chem., Int. Ed. 2001, 40, 1340.), the radicals were grouped in four different families, and the alkenes were selected from among those typical of polymer productions. All of the kinetic constants were calculated using density functional theory and classic transition state theory. Geometries of reactants, products, and transition states were determined at the B3LYP/6-311+G(d,p) level of theory, whereas reaction enthalpies, activation energies, and kinetic constants were estimated using different basis sets. By comparative evaluation of the results obtained with different basis sets, the best computational approach for each kinetic step was identified. As a result of this study, a computational methodology suitable for investigating a large number of kinetic pathways typical of free-radical polymerization processes is proposed.

Surgical technique to avoid bladder flap formation during cesarean section.

Cesarean section (CS) is now the most common major surgical procedure performed on women worldwide. A CS can be performed by either suturing or not suturing of the visceral peritoneum. Creation of the bladder flap is an integral step of the standard cesarean section. The bladder flap is made by superficially incising and dissecting the peritoneal lining to separate the urinary bladder from the lower uterine segment. It's still debated whether the formation of bladder flap is advantageous or not. If the uterine incision is made slightly above the vesicouterine peritoneal fold, the loose connective tissue between the uterus and the urinary bladder allows spontaneous descent of the bladder. Evidence on the role of the bladder flap in cesarean section is very limited. At present, it remains to be established whether there is any advantage in dissecting the bladder from the lower uterine segment during cesarean section.

The combination latanoprost-timolol versus twice daily 0.50% timolol administration either associated or not with latanoprost: efficacy and tolerability in the primary open-angle glaucoma.

AIMS: To evaluate the ocular hypotensive effects and tolerability of the once daily fixed combination latanoprost-timolol versus twice daily 0.50% timolol associated or not with once daily latanoprost in patients suffering from Primary Open-Angle Glaucoma (POAG). METHODS: We compared the effects of such a combination with those of 0.50% timolol alone twice daily in a group of 24 patients and with the effects of timolol 0.50% twice daily associated with once daily latanoprost in a second group of 20 patients with a follow-up of 24 months. RESULTS: In the first group of patients after one month the Intraocular Pressure (IOP) was reduced from a mean of 19.93 to a 17.04 mmHg. This reduction remained stable with a mean value of 17.00 mmHg at the third month, of 16.49 mmHg at the sixth month, of 17.04 at the twelfth month, 16.00 at the eighteenth month, and of 15.86 mmHg in the twenty-fourth month. In the second group there was a statistically significant reduction from 19.4 to 16.84 mmHg after one month. This reduction remained constant with mean values of 16.47 at the sixth month, of 16.20 at the twelfth month and of 16.00 mmHg at the twentyfourth month of treatment. CONCLUSIONS: The once daily latanoprost-timolol combination was shown to furtherly reduce the Intraocular Pressure (IOP) (p=0.001) and to maintain under control the intraocular pressure for the observation period (24 months). Both topical and systemic side-effects were scarse and tolerability was good.

Stickler syndrome in Pierre-Robin sequence prenatal ultrasonographic diagnosis and postnatal therapy: two cases report.

The Pierre-Robin Syndrome (PRS) is a rare congenital abnormality, with an approximately 1/30,000 estimated rate, characterized by the presence of the combination of mandibular hypoplasia (micrognathia or small jaw), glossoptosis (retrusion of the tongue into the pharyngeal airway) and, often, a posterior cleft of the secondary palate. It may be an isolated occurrence or part of a more complex syndrome and it is associated with long-term respiratory, nutritional, and developmental difficulties. Stickler syndrome (SS) is a rare autosomal dominant connective tissue disorder estimated to affect approximately 1/7500 newborns. It is diagnosed clinically and, at present, there is no consensus on a minimal clinical diagnostic criterion. The most frequent diagnosis in patients with syndromic Pierre Robin sequence is Stickler syndrome, which may be complicated by congenital high myopia and substantial risk of retinal detachment. However, cases of Stickler syndrome with probable visual complications are rarely identified among this group of patients by members of the cleft team. The patient had an acute unilateral hydrops, with a monolateral keratoconus. The ocular abnormalities included: severe myopia, abnormalities of the vitreous, and high risk of retinal detachment (with subsequent blindness). We report two extremely rare cases of prenatal diagnosis of PRS and SS, prematurely identified by prenatal ultrasonography and successively managed by oculists ophthalmogists.

[Pancreaticoduodenectomy for adenocarcinoma of the pancreatic head and papilla of Vater]. / Duodenocefalopancreatectomia per adenocarcinoma della testa del pancreas e della papilla di Vater.

AIM: The authors report their consecutive experience in the surgical management of adenocarcinoma (ADC) of head of pancreas and papilla of Vater, in order to review the available literature. METHODS: One hundred and seventy cases (131 in the head of pancreas and 39 in the papilla of Vater) were operated upon for ADC by radical pancreaticoduodenectomy in the period 1972-2005. The stomach was resected in 81 patients (47.7%) and the pylorus was preserved in 89 (52.3%). Follow-up was completed in all patients. RESULTS: Postoperative morbidity was reported in 66 patients (38.8%) and pancreatic fistulae were observed in 39 patients (22.9%). Postoperative mortality was 9.4% (16 patients), but in the last 10 years it was reduced to 4.1% (4/97 patients). Five-year survival for pancreatic ADC was 75% in stage IA, 43.9% in stage IB and IIA, 3.2% in stage IIB. In ADC of the papilla of Vater, for the same stages, the 5-year survival rates were 54.4%, 51.4%, 0% and 37.5%, respectively. None of the III-staged patients survived at a 5-year follow-up in both groups. CONCLUSIONS: Preoperative studies should include laparoscopy with cytological examination of peritoneal lavage, while preoperative biliary drainage is rarely indicated in case of obstructive jaundice. The Wirsung duct has to be anastomosed directly to the jejunum and the pancreatic section needs to be checked. Extended lymphadenectomy, in addition to the standard peripancreatic excision, is seldom indicated, there is no controindication to pylorus preservation and Wirsung drainage is not necessary. This operation should be performed in Centres with substantial experience.

EStokTP: Electronic Structure to Temperature- and Pressure-Dependent Rate Constants-A Code for Automatically Predicting the Thermal Kinetics of Reactions.

A priori rate predictions for gas phase reactions have undergone a gradual but dramatic transformation, with current predictions often rivaling the accuracy of the best available experimental data. The utility of such kinetic predictions would be greatly magnified if they could more readily be implemented for large numbers of systems. Here, we report the development of a new computational environment, namely, EStokTP, that reduces the human effort involved in the rate prediction for single channel reactions essentially to the specification of the methodology to be employed. The code can also be used to obtain all the necessary master equation building blocks for more complex reactions. In general, the prediction of rate constants involves two steps, with the first consisting of a set of electronic structure calculations and the second in the application of some form of kinetic solver, such as a transition state theory (TST)-based master equation solver. EStokTP provides a fully integrated treatment of both steps through calls to external codes to perform first the electronic structure and then the master equation calculations. It focuses on generating, extracting, and organizing the necessary structural properties from a sequence of calls to electronic structure codes, with robust automatic failure recovery options to limit human intervention. The code implements one or multidimensional hindered rotor treatments of internal torsional modes (with automated projection from the Hessian and with optional vibrationally adiabatic corrections), Eckart and multidimensional tunneling models (such as small curvature theory), and variational treatments (based on intrinsic reaction coordinate following). This focus on a robust implementation of high-level TST methods allows the code to be used in high accuracy studies of large sets of reactions, as illustrated here through sample studies of a few hundred reactions. At present, the following reaction types are implemented in EStokTP: abstraction, addition, isomerization, and beta-decomposition. Preliminary protocols for treating barrierless reactions and multiple-well and/or multiple-channel potential energy surfaces are also illustrated.

Acetylcholinesterase containing nerve fibres in coronary circulation.

The cholinergic innervation of coronary arteries and veins has been studied in the human. Structures resembling cholinergic nerve fibres are localised at the level of the extraparenchymal branches of the coronary arteries, organised in the adventitial plexus. Neither the coronary veins nor the intraparenchymal blood vessels are provided with a cholinergic innervation. Those findings are discussed.

The noradrenergic innervation of the ovary in old rats.

The influence of ageing on the noradrenergic innervation of the ovary was studied in female Wistar rats using high pressure liquid chromatography (HPLC) with electrochemical detection and catecholamine histofluorescence techniques. Old age was accompanied by a significant decrease in ovarian noradrenaline levels. In young animals (3-month-old) noradrenergic nerve fibres were distributed primarily to blood vessels and in lesser amounts to the interstitial glands. In aged animals (24-month-old) perivascular noradrenergic fibres were reduced by more than 40%; interstitial gland nerve fibres were reduced by approximately 20%. The possibility that impaired noradrenergic ovarian innervation occurring in old age may be in some way related with age-dependent failure in reproductive activity is discussed.

Nerve growth factor receptor immunoreactivity in the cerebellar cortex of aged rats: effect of choline alfoscerate treatment.

The rat cerebellar cortex represents an interesting animal model for the analysis of age-dependent changes in brain microanatomy and function. Moreover, the cerebellar cortex contains detectable amounts of nerve growth factor (NGF) and express NGF receptors, which are sensitive to aging. Previous studies of our group have shown that treatment with choline alfoscerate (alpha-glyceryl-phosphorylcholine) countered the loss of nerve cells and fibers occurring with age in the cerebellar cortex. The present study was designed to assess whether treatment for 6 months with a daily dose of 100 mg/kg of choline alfoscerate has any effect on the expression of NGF receptor immunoreactivity in male Wistar rats of 24 months of age. Twelve-month-old rats were used as an adult reference group. NGF receptor immunoreactivity which was developed in the 3 layers of the cerebellar cortex in adult rats was decreased in the neuropil of the molecular layer and in the cytoplasm of Purkinje neurons of rats of 24 months. The number of NGF receptor immunoreactive Purkinje neurons was also lower in the oldest age group, whereas the NGF receptor immunoreactivity in the cytoplasm of granule neurons was unchanged. Treatment with choline alfoscerate increased NGF receptor immunoreactivity in the molecular layer and in the cytoplasm of Purkinje neurons as well as the number of immunoreactive Purkinje neurons but was without effect on NGF receptor immunoreactivity in the granule neurons. These results suggest that choline alfoscerate treatment may increase the expression of NGF receptors in the rat cerebellar cortex.

Changes in glutathione content and localization in rat heart as a function of age.

The influence of aging on glutathione levels and distribution in the heart was studied in male Sprague-Dawley rats of 3 (young), 12 (adult) and 24 (old) months of age using biochemical and histofluorescence techniques, respectively. Biochemical assays of reduced glutathione (GSH) in the right and left ventricles and in the septum showed a significant decrease in GSH levels in adult in comparison with young animals. No further changes were noticeable between adult and old rats. GSH histofluorescence revealed a rather homogeneous distribution of the product of histochemical reaction within both right and left atria in 3-month-old rats. In 12-month-old rats a reduction of GSH histofluorescence in comparison with younger animals was noticeable. The loss is more consistent in the epicardial portion of the right atrium and in the endocardial region of the left atrium. In the atria of 24-month-old rats GSH reactivity was homogeneously distributed throughout the atrial wall and was significantly lower than in young or adult rats. In 3-month-old rats GSH histofluorescence was slightly lower in the epicardial than in the endocardial portions of both ventricles. In adult rats a significant decrease of GSH histofluorescence was noticeable in comparison with 3-month-old rats. The loss is particularly pronounced within the endocardial region of the left ventricle. In 24-month-old rats GSH histofluorescence showed no significant differences between adult rats. However, GSH was more homogeneously distributed throughout the ventricular wall than in adult animals. The significance of these data is discussed in relation to the role that GSH plays in protecting the myocytes against free radical damage.

Age-related changes of dopamine sensitive cyclic AMP generation in the rat frontal cortex.

The dopamine (DA) D-1 and D-2 receptors coupled to 3',5'-cyclic adenosine monophosphate (cAMP) generation were studied in membrane particles of the frontal cortex in young (3-month-old), adult (12-month-old) and aged (24-month-old) male Sprague-Dawley rats. Activation of D-1 receptors with DA, apomorphine or fenoldopam enhanced accumulation of cAMP in the frontal cortex of young rats. The stimulatory effect elicited by DA on cAMP generation declined by about 20% in adult rats. No further decline in cAMP accumulation was noticeable in aged animals. The response to dopaminergic agonists was blocked by the D-1 receptor antagonist SCH 29390 in the three age groups examined. The presence of D-2 receptors, negatively coupled to cAMP generation, was demonstrated by incubating frontal cortex membrane particles with SCH 23390 and then with DA. This inhibitory response, was also elicited with D-2 receptor agonists quinpirole or bromocriptine in the absence of SCH 23390 in which these compounds produced a decrease in cAMP. The decrease in cAMP caused following D-2 receptor stimulation was shown to be enhanced with age. No difference was observed between the three age groups of animals in the activation of cAMP production by forskolin. The present data suggest a selective decrease in the coupling between the D-1 receptor and cAMP generation in the frontal cortex of adult and aged rats and of an age-dependent increase in the coupling between the D-2 receptor and cAMP inhibition. The functional consequences of these biochemical changes may have important implications in the aging of the rat frontal cortex.

Occurrence of adrenergic nerve fibers and of noradrenaline in thymus gland of juvenile and aged rats.

Adrenergic nerve fibers (ANF) were studied in juvenile, adult and old rats by biochemical and morphological methods and by quantitative analysis of images (QAI). After chemical sympathectomy with neurotoxin 6-OH dopamine, the greater part of ANF disappeared. The whole thymus was drawn in juvenile normal or sympathectomized rats, in adult normal or sympathectomized rats and in old normal or sympathectomized rats. Thymuses from the above-mentioned animals were weighed, measured and dissected. Thymic slices were stained with eosin orange for the detection of the microanatomical details and with Bodian's method for the recognition of the whole nerve fibers. Histofluorescence microscopy was used for staining of ANF while immunofluorescence microscopy was employed for staining of neuropeptide Y (NPY)-like immunoreactivity. Biochemical dosage of proteins and of noradrenaline amount was performed. Finally, all morphological results were subjected to QAI. Our results suggest that: (1) total innervation of the thymus increases with age; (2) ANF do not change with age; (3) the content of noradrenaline in the thymus increases with age; and (4) NPY-like immunoreactive structures in the thymus decrease with age. Biochemical results are in accordance with the morphological ones and both are confirmed by means of QAI. The probable function of sympathetic innervation of rat thymus is also discussed.

Effect of interferon on human thymus microenvironment.

Interferon, a thymic immunostimulator, was used with the aim of assessing the importance of adrenergic nerve fibers (ANF) and/or AChE-positive nerve fibers (AChENF) in the regulation of some immunological functions in humans. Thymic normal control fragments and/or thymic fragments of immunostimulated patients were removed during surgical biopsies. Thymic slices were stained with eosin-orange (for the recognition of microanatomical details of the microenvironment) and with Bodian's method for staining of nerve fibers. Histofluorescence microscopy was employed for staining ANF. AChENFs were detected by means of the direct-coloring thiocholine method. All images were submitted to quantitative morphometrical analysis and statistical comparisons of data. Moreover, the amount of proteins and noradrenaline was measured on thymic homogenates of the same patients. Treatment with interferon induces substantial changes in the thymic microenvironment, on ANF, on AChENFs and on the total amount of proteins and noradrenaline in thymic tissue homogenates. In conclusion immunostimulation with interferon induces substantial changes in the whole thymus and in its microenvironment, involving both sympathetic and parasympathetic nerve fibers.