Neurotensin receptor 1 immunoreactivity in the peripheral ganglia and carotid body

In the present study we investigated, through immunohistochemistry, the presence and location of neurotensin receptor 1 (NTR1) in the peripheral ganglia and carotid body of 16 humans and 5 rats. In both humans and rats, NTR1 immunostained ganglion cells were found in superior cervical ganglia (57.4±11.6% and 72.4±11.4%, respectively, p<0.05), enteric ganglia (51.9±10.4% and 64.6±6.1%, p<0.05), sensory ganglia (69.2±10.7% and 73.0±13.1%, p>0.05) and parasympathetic ganglia (52.1±14.1% and 59.4±14.0%, p>0.05), supporting a modulatory role for NT in these ganglia. Positivity was also detected in 45.6±9.2% and 50.8±6.8% of human and rat type I glomic cells, respectively, whereas type II cells were negative. Our findings suggest that NT produced by type I cells acts in an autocrine or paracrine way on the same cell type, playing a modulatory role on chemoception

pPKCα mediated-HIF-1α activation related to the morphological modifications occurring in neonatal myocardial tissue in response to severe and mild hyperoxia

In premature babies birth an high oxygen level exposure can occur and newborn hyperoxia exposure can be associated with free radical oxygen release with impairment of myocardial function, while in adult animal models short exposure to hyperoxia seems to protect heart against ischemic injury. Thus, the mechanisms and consequences which take place after hyperoxia exposure are different and related to animals age. The aim of our work has been to analyze the role played by HIF-1α in the occurrence of the morphological modifications upon hyperoxia exposure in neonatal rat heart. Hyperoxia exposure induces connective compartment increase which seems to allow enhanced blood vessels growth. An increased hypoxia inducible factor-1α (HIF-1α) translocation and vascular endothelial growth factor (VEGF) expression has been found upon 95% oxygen exposure to induce morphological modifications. Upstream pPKC-α expression increase in newborn rats exposed to 95% oxygen can suggest PKC involvement in HIF-1α activation. Since nitric oxide synthase (NOS) are involved in heart vascular regulation, endothelial NOS (e-NOS) and inducible NOS (i-NOS) expression has been investigated: a lower eNOS and an higher iNOS expression has been found in newborn rats exposed to 95% oxygen related to the evidence that hyperoxia provokes a systemic vasoconstriction and to the iNOS pro-apoptotic action, respectively. The occurrence of apoptotic events, evaluated by TUNEL and Bax expression analyses, seems more evident in sample exposed to severe hyperoxia. All in all such results suggest that in newborn rats hyperoxia can trigger oxygen free radical mediated membrane injury through a pPKCα mediated HIF-1α signalling system, even though specificity of such response could be obtained by in vivo administration to the rats of specific inhibitors of PKCα. This intracellular signalling can switch molecular events leading to blood vessels development in parallel to pro-apoptotic events due to an immature anti-oxidant defensive system in newborn rat hearts

Olfactory Marker Protein in the Human Carotid Body

Background: Transduction mechanisms of the hypoxic chemoreflex elicited by carotid body (CB) chemoreceptor cells remain unclear. Recent studies direct attention to the plausible link between CB and olfactory chemoreceptor functions.Methods: Here we used immunohistochemistry to investigate the distribution and localization of olfactory marker protein (OMP) in human CB. Carotid bodies were collected post-mortem from hospital patients aged 27-76 years who died from reasons unre-lated to chronic pulmonary or cardiovascular disorders. We used specific antibodies to selectively identify CB cells and OMP in tissue sections. The binding of antibodies to target antigens was visualized with the Ultra Vision detection system.Results: We show that OMP is abundantly present in the cytoplasm of CB chemoreceptor cells. The presence of OMP in these cells indicates that the olfactory system may participate in shaping the chemosensory CB function.Conclusions: The findings support the notion that the transduction mechanisms of chemoreceptive systems contain a degree of homology, irrespective of the anatomical localization and the functional role these systems fulfill. The ectopic presence of OMP in CB broadens the current understanding of the mechanisms underlying chemosensory responses

KISS1 and KISS1R expression in the human and rat carotid body and superior cervical ganglion

KISS1 and its receptor, KISS1R, have both been found to be expressed in central nervous system, but few data are present in the literature about their distribution in peripheral nervous structures. Thus, the aim of the present study was to investigate, through immunohistochemistry, the expression and distribution of KISS1 and KISS1R in the rat and human carotid bodies and superior cervical ganglia, also with particular reference to the different cellular populations. Materials consisted of carotid bodies and superior cervical ganglia were obtained at autopsy from 10 adult subjects and sampled from 10 adult Sprague-Dawley rats. Immunohistochemistry revealed diffuse expression of KISS1 and KISS1R in type I cells of both human and rat carotid bodies, whereas type II cells were negative. In both human and rat superior cervical ganglia positive anti-KISS1 and -KISS1R immunostainings were also selectively found in ganglion cells, satellite cells being negative. Endothelial cells also showed moderate immunostaining for both KISS1 and KISS1R. The expression of both kisspeptins and kisspeptin receptors in glomic type I cells and sympathetic ganglion cells supports a modulatory role of KISS1 on peripheral chemoreception and sympathetic function. Moreover, local changes in blood flow have been considered to be involved in carotid body chemoreceptor discharge and kisspeptins and kisspeptin receptors have also been found in the endothelial cells. As a consequence, a possible role of kisspeptins in the regulation of carotid body blood flow and, indirectly, in chemoreceptor discharge may also be hypothesized

Anatomical basis of erector spinae plane block: a dissection and histotopographic pilot study

Purpose: Erector spinae plane (ESP) block is an interfascial blockade used in different clinical scenarios. This study investigated the ventral extent of dye diffusion in ESP block. Methods: The ultrasound-guided ESP block was bilaterally performed with an injection at the T5 vertebral level (21-Gauge, 50\ua0mm needle), using diluted black tissue marking dye (20\ua0mL; 1:4 ratio with standard saline solution) instead of local anesthetic on two fresh-frozen corpses within the body donation program of the University of Padova. Subsequently, the gross anatomical dissection was performed by a combined posterior plus anterior approach, and the histotopographic examination completed. Results: Macroscopically by gross anatomical dissection, the dye spreading ranged on the dorsal side of the chest from T2/3 to T10/11 with an extension up to 10\ua0cm laterally, and on the ventral side of the chest from T2/3\u2013T9/10. Microscopically by histotopographic examination, the dye diffused ventrally to the intercostal spaces (2\u20133 and 5\u20136 spaces on the right and left, respectively) by following the blood vessels coupled to the dorsal nerve passing through the costotransverse foramen. Conclusions: The anterior pathway of dye diffusion from the site of injection within the erector spinae muscle group during an ESP block seems to follow the blood vessels and dorsal rami of spinal nerves, suggesting the passing through the costotransverse foramen to reach the anterior paravertebral space and the intercostal nerves. These findings display an anterior histotopographic diffusion of dye resembling a paravertebral block

A light on the dark side: In vivo endoscopic anatomy of the posterior third ventricle and its variations in hydrocephalus

Objective: Despite the technological advancements of neurosurgery, the posterior part of the third ventricle has always been the "dark side"of the ventricle. However, flexible endoscopy offers the opportunity for a direct, in vivo inspection and detailed description of the posterior third ventricle in physiological and pathological conditions. The purposes of this study were to describe the posterior wall of the third ventricle, detailing its normal anatomy and surgical landmarks, and to assess the effect of chronic hydrocephalus on the anatomy of this hidden region. Methods: The authors reviewed the video recordings of 59 in vivo endoscopic explorations of the posterior third ventricle to describe every identifiable anatomical landmark. Patients were divided into 2 groups based on the absence or presence of a chronic dilation of the third ventricle. The first group provided the basis for the description of normal anatomy. Results: The following anatomical structures were identified in all cases: adytum of the cerebral aqueduct, posterior commissure, pineal recess, habenular commissure, and suprapineal recess. Comparing the 2 groups of patients, the authors were able to detect significant variations in the shape of the adytum of the cerebral aqueduct and in the thickness of the habenular and posterior commissures. Exploration with sodium fluorescein excluded the presence of any fluorescent area in the posterior third ventricle, other than the subependymal vascular network. Conclusions: The use of a flexible scope allows the complete inspection of the posterior third ventricle. The anatomical variations caused by chronic hydrocephalus might be clinically relevant, in light of the commissure functions

A proposed design for the evaluation of change in a small reference group.

Herpes Simplex Virus type 1 (HSV-1), a neurotropic pathogen widespread in human population, infects the enteric nervous system (ENS) in humans and rodents and causes intestinal neuromuscular dysfunction in rats. Although infiltration of inflammatory cells in the myenteric plexus and neurodegeneration of enteric nerves are common features of patients suffering from functional intestinal disorders, the proof of a pathogenic link with HSV-1 is still unsettled mainly because the underlying mechanisms are largely unknown. In this study we demonstrated that following intragastrical administration HSV-1 infects neurons within the myenteric plexus resulting in functional and structural alterations of the ENS. By infecting mice with HSV-1 replication-defective strain we revealed that gastrointestinal neuromuscular anomalies were however independent of viral replication. Indeed, enteric neurons exposed to UV-inactivated HSV-1 produced monocyte chemoattractant protein-1 (MCP-1/CCL2) to recruit activated macrophages in the longitudinal muscle myenteric plexus. Infiltrating macrophages produced reactive oxygen and nitrogen species and directly harmed enteric neurons resulting in gastrointestinal dysmotility. In HSV-1 infected mice intestinal neuromuscular dysfunctions were ameliorated by in vivo administration of (i) liposomes containing dichloromethylene bisphosphonic acid (clodronate) to deplete tissue macrophages, (ii) CCR2 chemokine receptor antagonist RS504393 to block the CCL2/CCR2 pathway, (iii) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and AR-C 102222 to quench production of nitrogen reactive species produced via iNOS. Overall these data demonstrate that HSV-1 infection makes enteric neurons recruit macrophages via production of a specific chemoattractant factor. The resulting inflammatory reaction is mandatory for intestinal dysmotility. These findings provide insights into the neuro-immune communication that occurs in the ENS following HSV-1 infection and allow recognition of an original pathophysiologic mechanism underlying gastrointestinal diseases as well as identification of novel therapeutic targets

The human area postrema and other nuclei related to the emetic reflex express cAMP phosphodiesterases 4B and 4D

Phosphodiesterase 4 (PDE4) inhibitors, i.e. rolipram, are being extensively investigated as therapeutic agents in several diseases. Emesis is one of the most common side effects of PDE4 inhibitors. Given the fact that the area postrema is considered the chemoreceptor trigger zone for vomiting, the present study investigates the regional distribution and cellular localization of the four gene transcripts of the PDE4 subfamily (PDE4A, PDE4B, PDE4C and PDE4D) in human brainstem. In situ hybridization histochemistry was used to locate the mRNA distribution of the four PDE4 subfamilies in the area postrema and related nuclei of human postmortem brainstem. We have found that in the brainstem PDE4B and PDE4D mRNA expression is abundant and distributed not only in neuronal cells, but also in glial cells, and on blood vessels. The hybridization signals for PDE4B and PDE4D mRNAs in the area postrema were stronger than those in any other nuclei in the brainstem. They were also found in vomiting-related nuclei such as the nucleus of the solitary tract and the dorsal vagal motor nucleus. These findings suggest that cAMP signaling modification in the area postrema could mediate the emetic effects of PDE4 inhibitors in human brainstem.This work was supported by grants from Ministerio de Educación y Ciencia and Fondo Europeo de Desarrollo Regional (SAF2006-10243). F.M. was on sabbatical leave from Hirosaki University School of Medicine. S.P.-T. was recipient of a predoctoral fellowship from CIRIT (Generalitat de Catalunya).Peer Reviewe

Hallux valgus and fusion of the middle phalange of V ray

Hallux valgus (HV) is a foot deformity commonly seen in medical practice, often accompanied by significant functional disability and foot pain. Its prevalence in the adult population is in 23% in adults (18-65 years) and 35.7% in elderly people (over 65 years) and is higher in females (30% compared to males 13%). The anatomical variation of the lateral rays has been ascribed to the process of involution of the feet and of its functions and actions. The intermediate phalanges of the V ray can be fused or also reduced in volume. The aim of the study was to evaluate a possible association between HV and anatomical variation of V ray. The standard radiographs of 100 patients (M 21, F 79, mean age 53y) with clinical diagnosis of HV were analysed. The HV angle was 29.84 (range 16.9 - 62,5), the 1-2 intermetatarsal angle was 10.92 (range 6.93-16.63) and the hallux interphalangeal angle was 10.55 (range 1,8 – 35.3). In 98% of cases there was the presence of fusion of the phalanges. A series of 100 consecutive patients (M 25, F 75, mean age 48y) were also analysed and basing on the review of the standard radiographs the fusion of the middle phalange was found in 42% of cases. There are conflicting notions about aetiology of HV as well. Occupation, shoe wear, genetic predisposition, and pes planus have been implicated. Our study show a strong association between the HV and fusion of the middle phalange. The presence of an anatomical variation of the V ray could modify the biodynamic of the walk and consequently influence the development and progression of the HV

Anatomical study and clinical implication of perivascular fascia of the radial artery

The characteristics of the fascial tissue that surround a vascular bundle are rarely described in any anatomical textbook and often neglected in the histological description of a vascular structure. The ability of a vascular structure to adapt to any body movement, to maintain its calibre against external pressure preserving its functional role is guarantee by this perivascular fascia. Wrist ganglions are the most common masses localized on the dorsal and volar aspect of the wrist. The herniation of the synovial sac or a split in the synovial epithelium of the volar wrist joint produce a ganglion that is able to distort and compress the radial artery. Authors present the case of 24 years old man with a mucinous cyst originated from the volar wrist joint that was grown inside the vascular fascia of the radial artery and extended up to the middle portion of the forearm. Clinical sintomatology of pain and tenderness was justify by the temporary partial decrease of the arterial lumen and occlusion of the satellite veins. To better understand the clinical relevance of these fascial tissue a microscopical study of serial sections of the radial artery in 20 cadaveric upper limbs was performed (EE, Azan-Mallory, Weigert). The mean area of the perivascular fascia was 13596,3 mm, the mean minimum and maximum thickness of this area was 73 and 389 micron. The mean thickness of the fibrous tissue of the perivascular fascia was 26,21 micron. During the raising of a forearm pedicled radial artery flap or during the surgical excision of volar wrist ganglions the surgeon has to mobilize the radial artery thanks to the integrity of its perivascular fascia. The fascia surrounding the radial artery and satellite veins represented a inestensive sleeve that compelled the mucinous cyst to grow flattened proximally until its complete erniation and superficial radial nerve dislocation in the middle of the forearm. Other clinical implications of the alteration of the radial perivascular fascia are described