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Reinke’s edema is a benign disease of the human vocal fold, which mainly affects the sub-epithelial layer of the vocal fold. Micro­scopic observations show a strongly oedematous epithelium with loosened intercellular junctions, a disruption of the extracellular connections between mucosal epithelium and connective tissue, closely adherent to the thyroarytenoid muscle. Thickening of the basal layer of epithelium, known as Reinke’s space, high deposition of fibronectin and chronic inflammatory infiltration it is also visible. We analyzed, together with the hepatocyte growth factor (HGF), the expression level of MIB-1 in samples harvested from patients affected by Reinke’s edema, in order to define its biological role and consider it as a possible prognostic factor in the follow-up after surgical treatment. We observed a moderate expression of HGF in the lamina propria of the human vocal fold and in the basal membrane of the mucosal epithelium. Our finding suggests that this growth factor acts as an anti – fibrotic agent in Reinke’s space and affects the fibronectin deposition in the lamina propria. MIB-1, on the contrary, showed a weak expression in the basement membrane of the mucosal epithelium and a total absence in the lamina propria deep layer, thus suggesting that only the superficial layer is actively involved in the reparatory process with a high regenerative capacity, together with a high deposition of fibronectin. The latter is necessary for the cellular connections reconstruction, after the inflammatory infiltration.

Gallbladder carcinoma is the most common biliary tract tumor and the fifth most common gastrointestinal tract cancer .The prognosis of gallbladder carcinoma is poor and less than 5% of the patients are still alive five years postoperatively.1 Gallbladder specimens were obtained during surgical operations performed in eleven patients for resection of a gallbladder carcinoma, and during five autopsies (control cases selected among patients who died from for other causes, excluding those suffering from biliary or hepatic diseases). Immunohistochemical characterization and distribution of neurotrophins, with their respective receptors, were analyzed. The actual role played by these neurotrophic factors in the general regulation, vascular permeability, algic responsiveness, release of locally active substances and potential tumorigenesis in the gallbladder and biliary ducts compartment remains controversial. Our study revealed an increased immunohistochemical expression of NGF and TrKA in the epithelium and in the epithelial glands of the gallbladder carcinoma together with an evident immunoreactivity for BDNF in the same neoplastic areas. An evident immunoreactivity for NGF, TrKA and BDNF was observed in control specimens of gallbladder obtained during autopsies, whereas a weak or quite absent immunoreactivity was observed in the same specimens for NT4, TrKC and p75. On the contrary an appreciable immunoreactivity for p75 was observed in the specimens harvested from patients with gallbladder carcinoma. We also investigated the expression of some known tumor markers such as MIB-1 (anti Ki-67), CD34 and CA15-3, to identify a possible correlation between the expression of these molecular factors and the prognosis of gallbladder carcinoma. They resulted highly expressed in the stroma (CD34 and CA 15-3) and in the epithelium/epithelial glands (MIB-1) of the neoplastic areas and appeared to be almost absent in the control cases, suggesting that these markers, taken together, could be adopted as a panel of prognostic factors in the evaluation of the gallbladder carcinoma.

Objective: The lower limbs are frequently involved in neurovascular compression syndromes, owing to their anatomical, vascular and muscular characteristics and to the orthostatic position. These syndromes were identified by exclusion, using neuroimaging techniques and treated by microsurgical techniques., Methods: Eight patients with a neurovascular compression syndrome due to venous vascular lesions in the lower limbs (popliteal fossa, proximal and medial third of the inferior limb, tarsal tunnel) were selected. The symptomatology was characterized by pain, Tinel's sign, hyperalgesia, allodynia, numbness along the nerve course and foot weakness: all were exacerbated by the standing position, thus suggesting a neurovascular compression syndrome. Diagnostic tools comprised Doppler ultrasonography, Electromyography, CT 3D and MRI. Treatment consisted of microsurgery with neurovascular dissection., Results: Following surgical treatment, rapid pain relief and a partial recovery of neurological deficits (including the ability to walk) was observed within 8-10 months., Conclusion: An early diagnosis of NCS using various neuroimaging techniques and prompt treatment may improve the response to surgical therapy. The aim of the case studies described is to improve understanding of these pathologies thus enabling correct clinical decisions.

Jugulo-tympanic paragangliomas are the most common primary neoplasm of the middle ear, but little is still known about the histological features differentiating the benign and malignant forms. We investigated, with an immunohistochemical procedure, the expression of neurotrophins with their receptors, in fifteen samples of paragangliomas, and MIB-1 in order to consider them as prognostic factors of malignancy. We observed a general positivity for NGF - TrKA - NT4 - TrKC in the cytoplasm, and a strong expression for BDNF in the extracellular space. MIB-1 was moderate in the nucleus of neoplastic cells, weak in the cytoplasm and totally absent in the extracellular space. The comparison between the clinical recurrences and the rate of cytoplasmatic neurotrophins showed strong immunoreactivity in recurrent patients. It should be emphasized that 2 of the 3 recurrences had a wider distribution of the neutrophins, leading to hypothesize the involvement of these substances in the cell proliferation of glomus tumors. Malignant forms of these rare glomus tumors cannot be clearly identified using MIB-1 as a prognostic marker, although we can affirm that neurotrophins and their receptors can be considered as a panel of potential diagnostic markers to monitor the development of such malignancies. Although the small number of patients does not allow definitive conclusions to be made, our findings showed a possible trend towards significance which requires a more powerful study to evaluate this further.

Atherosclerosis is a degenerative disease whose role in the onset and development of cardiovascular pathologies and complications is of importance. Due to its silent but progressive development, and considering the endothelial, immunological and inflammatory processes that are involved in its clinical course, this still relatively unknown pathological condition has been and continues to be a matter of investigation worldwide. Our experience with previous studies on atherosclerosis led us to investigate the possible influence of a low molecular weight heparin (LMWH) - Parnaparin® on the development and clinical course of atherosclerosis in double knock-out laboratory animals (ApoE-/- mice). Our experiments demonstrated a possible role of Parnaparin (PNP) in the control of atherogenic disease. In fact, in treated mice vs. untreated ones, PNP reduced the number and the size of atherosclerotic lesions in the aortic wall, as well as the development of liver steatosis, which was massive in untreated animals and moderate in treated ones. These preliminary observations require further clinical studies, but demonstrate a possible role of Parnaparin in the control of the development and clinical evolution of atherosclerosis and liver steatosis in laboratory animals.

The immunohistochemical profile of neurotrophins and their receptors in the human cranial dura mater was studied by examining certain dural zones in specimens harvested from different regions (frontal, temporal, parietal and occipital). Dural specimens were obtained during neurosurgical operations performed in ten patients for surgical treatment of intracranial lesions (meningiomas, traumas, gliomas, vascular malformations). The dural fragments were taken from the area of the craniotomy at least 8 cm from the lesion as well as from the area in which the meningioma had its dural attachment. Immunohistochemical characterization and distribution of neurotrophins, with their receptors, were analyzed. The concrete role played by these neurotrophic factors in general regulation, vascular permeability, algic responsivity and release of locally active substances in the human dura mater is still controversial. Our study revealed a general structural alteration of dural tissue due to the invasivity of meningiomatous lesions, together with an improved expression of brain derived neurotrophic factor (BDNF) in highly proliferating neoplastic cells and an evident production of nerve growth factor (NGF) in inflammatory cells, suggesting that BDNF has a role in supporting the proliferation rate of neoplastic cells, while NGF is involved in the activation of a chronic inflammatory response in neoplastic areas.

Lymphoid organs are supplied by many nerve endings associated with different kinds of cells and macrophages. The role of this innervation on the release of locally active molecules is still unclear. Lingual tonsils belong to Waldeyer's Ring, in close association with palatine tonsils and nasopharyngeal (adenoids) tonsils, thus constituting part of NALT (nasal-associated lymphoid tissue) together with the tubal tonsils and lateral pharyngeal bands. In this study, we focused our attention on the expression of some neurotrophins (NTs) and their high- and low-affinity receptors in human lingual tonsils. Light immunohistochemistry showed that human tonsillar samples were generally positive for all the NTs investigated (NGF, BDNF, NT-3, NT-4) and their receptors (TrKA, TrKB, TrKC and p75) with some different expression levels. NGF and TrKC were strongly expressed in macrophages, but weakly in lymphocytes. However, BDNF and TrKB was highly expressed in lymphocytes and weaker in macrophages. The low-affinity receptor for NGF, p75, was mainly moderately expressed in the analysed samples. These results suggest the presence of a pattern of neurotrophin innervation in the human lingual tonsil which may play a role in sustaining inflammatory conditions and in modulating a close interaction between the nervous system and the different immune cellular subtypes.

Compared to the normal epidermal epithelium, cholesteatomas have altered growth properties characterized by the excessive growth of keratinocytes leading to mucosal destruction. Either congenital or acquired, these lesions, which grow in the middle ear space, the petrous apex or the mastoid of temporal bones, are mostly considered benign skin tumoral lesions. However, many questions remain concerning their pathophysiology. Numerous studies have been proposed to identify those cholesteatoma lesions at risk of recurrence, a possible event that may cause hearing loss. We examined patients with petrous apex or mastoid cholesteatoma in order to analyze the expression of various neurotransmitters, neurotrophins and their receptors and the Ki-67 antigen for identification of a possible relationship between clinical outcome and histopathological behaviour in terms of the proliferative activity of cholesteatomas. Expression of the analyzed molecules was studied using immunohistochemical methods in seven adult patients with petrous apex cholesteatoma who underwent surgical removal of the lesion. Our results, in accordance with published data, confirm that Molecular Immunology Borstel-1 (MIB-1) and certain neurotransmitters could be useful in the prognostic evaluation of the risk of recurrence of aggressive forms of cholesteatoma.