Biomedical subjects
Publications and source records attributed to P Poggi.
The Authors report two cases of splenectomy for trauma, followed by heterotopic autotransplantation of splenic tissue in omental pockets. A follow-up nuclear scan and ultrasonography showed function and growth of the splenic implants. The pertinent surgical literature is reviewed.
The characteristics of the lymphatic vessel endothelial wall have been investigated in human normal and inflamed dental pulps. In normal pulps the endothelial wall is characterized by the presence of micropinocytotic vesicles and intraparietal channels. In the inflamed pulpal tissue, where an increase in interstitial fluid pressure occurs, the distended endothelial wall presents open junctions between endothelial cells and the openings of the intraparietal channels. Moreover the micropinocytotic vesicles disappear. The cytoplasm of the endothelial cells is characterized by the presence of numerous Weibel-Palade bodies, which increase in number in the dilated vessels. In the fibrillar apparatus surrounding the lymphatic vessel wall collagen fibrils are the prevalent component, while elastic fibers are not present. The different morphological properties of the lymphatic vessels are compared and discussed with regard to the variation of the functional conditions of the tissue.
The immotile-cilia syndrome (ICS) is a congenital disorder characterized by dysmotility or even complete immotility of the cilia in the ciliated epithelia. The most frequent consequences include recurrent airway infections from early childhood. Neonatal asphyxia often occurs. Males are usually sterile, whereas females may be fertile or infertile. The disease is inherited as an autosomal recessive trait, but previous attempts to localize the ICS susceptibility gene have so far been unsuccessful. Here, we present the case of two sib pairs affected by ICS from two unrelated families. The electron microscopic investigation of nasal biopsies showed structural anomalies of the cilia, characterized by single microtubules or doublets, arranged randomly in the axoneme. Histocompatibility antigen (HLA)-genotyping of all family members revealed: 1) a significant association of ICS with the HLA-DR7; DQW2 haplotype, which is shared by all the affected sibs (P = 0.0099; RR = 25.94); 2) a possible linkage of the ICS susceptibility gene with HLA, both the affected sibs being HLA-identical, the healthy brother in family B being HLA-different (sib-pair analysis: P less than 0.001).
Myotonic dystrophy is an hereditary disorder of several organ systems. Skeletal muscle is a principal target organ, but abnormalities also occur in the peripheral microcirculation. Because morphological and functional changes in the dermal blood microcirculation may affect interstitial fluid drainage of the skin, we examined dermal lymphatic morphology in adult patients with myotonic dystrophy. Skin biopsies were taken from the big toe from patients with myotonic dystrophy (age 18-50 years) and subjected to light and electron microscopy; five healthy subjects served as controls. The salient findings in myotonic dystrophy were ultrastructural changes of the lymphatic endothelial cells and the fibrillar elements that surround the lymphatic wall. These abnormal lymphatic findings are interpreted in light of changes in the blood microvasculature and loose connective tissue in this disorder.
The production of oxygen-free radicals has been proposed as a determinant of the delayed toxicity of doxorubicin. The aim of the present investigation was to evaluate the potential cardioprotective effect of superoxide dismutase (SOD) and catalase (CAT) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a rat model. Female Sprague Dawley rats received 3 mg/kg of DXR intravenously weekly for 4 weeks. SOD or CAT were administered intravenously at the dose of 10000 U/kg 2 min before and 30 min after each DXR administration. Cardiac toxicity was monitored by means of electrocardiography (QaT interval) and by light and electron microscopy evaluation of left ventricle fragments. DXR treated rats showed, in comparison with control animals, a decrease of body weight gain, a progressive and irreversible prolongation of QaT and significant morphologic lesions consisting in myocyte vacuolization and myofibrillar loss. SOD significantly prevented the impairment of body weight gain and QaT prolongation. Moreover, morphologic lesions were significantly reduced in rats receiving DXR + SOD. On the contrary, CAT seems to be completely devoid of protective effect.
A case of an undetected myocardial infarction in a patient with diabetes mellitus in which the first clinical sign was a syncope due to rupture of the left ventricular inferior wall is described. Survival was enhanced by a fast diagnosis (aided by the availability of an ECO 2D in the emergency room), by emergency pericardiocentesis with temporary haemodynamic stabilization and by prompt access to the Cardiosurgical Unit. A prompt diagnosis and treatment can allow the survival of patients, even in the extreme case that the ventricular wall rupture represents the first clinical manifestation of the myocardial infarction. The left ventricular free wall rupture in the course of myocardial infarction has a subacute pattern in about 30%, due to various mechanisms such as thrombosis or pericardial adherence over the ruptured wall.
The distribution in oral tissues of endothelin, a multifunctional peptide originally identified within endothelial cells, and subsequently in some epithelial cells, neurons and neuroendocrine cells, has not been investigated yet. We have studied the localization of endothelin-like immunoreactivity in human tooth germ and mature dental pulp by immunohistochemical techniques. Such immunoreactivity was detected only within endothelial cells in both mature dental pulp and developing tooth. Arteries and veins of various sizes as well as small thin vessels displayed endothelin-like immunoreactivity. In the tooth germ, the cells of the enamel organ or the precursors of the odontoblasts were found unreactive. In the mature pulp, no cells of the stroma or nerves displayed endothelin-like immunoreactivity. These findings suggest that vascular endothelium may be the only source of endothelin in human dental tissues. It is tentatively proposed that endothelin released in mature tooth pulp may participate in the regulation of the pulpal blood flow. Although the possible role of endothelin in developing tissues is far from being clear, the mitogenic effects and the proto-oncogenes expression induced by endothelin in some cells raise the possibility that this peptide might also play a role during tooth development.
The aim of the present investigation was to evaluate the potential cardioprotective effect of reduced glutathione (GSH) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a well-documented rat model. DXR was administered i.v. at a weekly dose of 3 mg/kg for a total of 4 doses; 250 or 500 mg/kg of GSH was given i.v. 10 min before and 2 h after each DXR injection, resulting in a total weekly dose of 500 or 1000 mg/kg, respectively. The development of cardiotoxicity was monitored in vivo by means of electrocardiography (QaT duration), and was evaluated by measuring the contractile performance of isolated atria and by light and electron microscopy of left ventricular samples excised 5 weeks after the last DXR administration. DXR was found to impair body weight gain and to produce an irreversible and time-dependent prolongation of QaT, a decrease in myocardial contractility of isolated atria and typical morphologic alterations, including myocyte vacuolization and myofibrillar loss. Pretreatment with GSH at a dose of 500 mg/kg x 2, but not at 250 mg/kg x 2, partially prevented the impairment of body weight gain, QaT prolongation in ECG and the decrease in myocardial contractility of isolated atria induced by DXR. Alterations of the morphologic pattern were also significantly reduced in animals receiving the higher dose of GSH. Determinations of the cardiac non-protein sulfhydryl group content showed that GSH, at doses higher than or equal to 500 mg/kg, significantly increased this parameter, irrespective of the presence of DXR. In conclusion, the present data indirectly support the hypothesis that oxidative damage is involved in DXR cardiotoxicity and indicate that maintenance of the reduced thiol pool could be an important issue in myocardial protection.
The calcium antagonist flunarizine (FLN) was tested for its ability to prevent doxorubicin (DXR)-induced cardiotoxicity in the rat. A cumulative dose of 9.0 mg/kg of DXR was administered i.v. over a period of 1 week. FLN (10 mg/kg/day i.p., 6 days/week) was administered according to two different time schedules, covering respectively the first and last 4 weeks after the beginning of DXR treatment. The two schedules were adopted to assess whether early and/or delayed DXR-induced cardiotoxic effects were affected by FLN. The development of cardiac toxicity was monitored by ECG recordings. The animals were sacrificed 8 weeks after the beginning of DXR treatment. The contractile performance of isolated atria and the morphological pattern of left ventricular fragments were subsequently evaluated. The early administration schedule of FLN was shown to be ineffective in preventing DXR-induced cardiotoxicity and in some cases was actually found to potentiate the effects of DXR. In contrast, the histological evaluation of ventricular preparations from rats treated with DXR and FLN according to the delayed time schedule showed a significant improvement with respect to hearts from animals treated with DXR alone. An inhibition of the delayed calcium overload occurring after DXR administration has been proposed as a possible mechanism for this protective action.
The lymphatic vessels of the dental pulp have been studied in non-carious teeth of young people. A network of lymphatic vessels drains the pulpal tissue. The lymphatic capillaries are characterized by a thin wall with an irregular profile. Cellular projections rise from the endothelial cells. Micropinocytotic vesicles and intercellular adjoining structures are the main mechanisms for the lymph formation. Multivesicular structures, Weibel-Palade bodies and paracrystalline inclusions have been observed.
Diaphragms of fetal, neonatal and young albino rats have been observed both under light and electron microscopes to examine the presence and distribution of lymphatic vessels and their morphological features. In fetal diaphragms of between 18 and 22 days of gestation, no normal lymphatic vessels can be seen; only after birth, specifically in neonatal and 2-day-old rats, small lymphatic vessels appear; they are in close proximity to the blood vessels in the inner areas of the muscle. As the rats get older, lymphatic vessels are also observed in the subserosa where an abundant connective tissue is present. The fine structure of diaphragmatic lymphatic vessels is different at different ages. In neonatal rats of up to 2 days, the endothelial wall is very thin and often holed. The relationships between contiguous endothelial cells are characterized by simple end-to-end or overlapping structures. The basement membrane is virtually absent. Within the first week of life, the endothelial wall becomes more complex; along the wall, complex interdigitations between two contiguous endothelial cells often touch. A discontinuous basement membrane and collagen and elastic fibers surround the vessels. In the older rats (from 14 to 25 to 140 days), next to the complex interdigitations which characterize the junction between two contiguous endothelial cells, cellular flaps interdigitate forming a channel which opens out either to the exterior or the interior of the vessel. Dense bundles of elastic and collagen fibers are closely apposed to the endothelial wall.
The production of oxygen free radicals during anthracycline therapy has been proposed as a determinant of the toxicity of anthracyclines. Oxygen radical generation might specifically affect the myocardium because of the low antioxidant defense systems in cardiac tissue. The aim of the present investigations was to evaluate the potential cardioprotective effect of superoxide dismutase (SOD) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a rat model. Female Sprague Dawley rats received 3 mg/kg of DXR intravenously weekly for 4 weeks. SOD was administered intravenously at the dose of 10,000 U/Kg one minute before and 30 minutes after each DXR administration. Cardiac toxicity was monitored in vivo by means of electrocardiography (QaT interval), by determining the contractile properties of isolated atria, and by light and electron microscopy evaluation of left ventricle fragments excised 5 weeks after the last DXR administration. The degree of morphologic lesions was quantitated according to the score system proposed by E. Billingham. DXR treated rats showed, in comparison with control animals treated with saline a decrease of body weight gain, a progressive and irreversible prolongation of QaT, decrease of contractility of isolated atria, and significant morphologic lesions consisting in myocyte vacuolization and myofibrillar loss. SOD significantly prevented the impairment of body weight gain, QaT prolongation and the impairment of myocardial contractility. Moreover morphologic lesions were significantly reduced in rats receiving DXR + SOD. The present data indicate that SOD could represent an important issue in myocardial protection against DXR cardiotoxicity.
The ultrastructural characteristics of the lymphatic capillaries of the rabbit heart were examined by scanning and transmission electron microscopy (SEM and TEM) using similar technical preparation. SEM defined the interrelationships between endothelial cells including the pocket-like structures formed by overlapping between cells and the corresponding intercellular bridges. Except for rare spindle cells apposed on the luminal surface of the endothelium seen only on SEM, these features were confirmed by TEM. On the abluminal side of the lymphatic capillary wall, a rich network of filaments and fibrils was detectable using both ultrastructural techniques. These two modalities (SEM and TEM) complement one another in defining the microanatomy of the lymphatic capillary.
The peptidergic innervation of human dental pulp was studied with indirect immunofluorescence and immunoperoxidase techniques. Pulpal nerve fibres displaying immunoreactivity for cholecystokinin, calcitonin gene-related peptide, C-terminal flanking peptide of neuropeptide tyrosine, leucine-enkephalin, methionine-enkephalin, neuropeptide K, neuropeptide tyrosine, peptide with N-terminal histidine and C-terminal isoleucine, somatostatin-28, substance P and vasoactive intestinal polypeptide were observed. Immunoreactive axon varicosities were detectable within radicular and coronal nerve trunks and within the nerve plexus of Raschkow in the para-odontoblastic region. Many peptidergic nerve fibres were observed in association with blood vessels of various sizes. Substance P- and calcitonin-gene-related peptide-immunoreactive axons were visible in the odontoblastic layer. The occurrence of VIP- and PHI-immunoreactive fibres lends support to the hypothesis that human tooth may be supplied by parasympathetic nerves. The immunocytochemical results here shown provide a morphological basis to previous experimental studies concerning the possible roles of neuropeptides in nociception mechanisms, control of the blood flow and modulation of the inflammatory response in dental tissues.
A 35 year old homosexual man showed clinical features of myopathy, with progressive muscular weakness of proximal muscles. EMG demonstrated a myopathic pattern; serum CPK was mildly elevated and CSF examination revealed antibodies to HIV and a blood-brain barrier damage. An open biopsy of the quadriceps femoris muscle showed myopathic changes with inflammatory features including a marked variation in fiber size, necrotic fibers and phagocytosis, a profusion of internal nuclei. Fiber type analysis with myosin ATPase reaction revealed that myopathic changes involved both fiber types. Changes in the oxidative enzyme activities were also observed in the degenerating muscle fibers. Electron microscopy showed patterns of myofibrillar degeneration and characteristic rod bodies in 30% of fibers. The close resemblance of the present morphological results with those recently observed in some HIV antibody positive men seems to indicate the existence of a specific structural myopathy associated with AIDS.
The occurrence and distribution of protein p38 (synaptophysin) were investigated by immunofluorescence. Immunoreactivity for protein p38-like antigen was detected within axons of radicular nerve trunks entering the tooth and within nerve terminals close to blood vessels. Immunoreactive structures were also observed in the para-odontoblastic region. It is proposed that protein p38, translocated within small synaptic vesicles from neuronal perikarya along the axons, may be a reliable marker for detection of nerve endings in human tooth.
Nerve fibres displaying such immunoreactivity were revealed by indirect immunofluorescence. Neuropeptide K-like immunoreactive fibres, entering the pulp within large nerve trunks, were distributed around blood vessels as well as in the stroma. Some immunoreactive fibres were also observed in the para-odontoblastic region. In view of the biological activity of neuropeptide K, it is tentatively proposed that it may act in the dental pulp as a regulatory peptide involved in neurogenic inflammation, blood flow regulation and sensory transmission.
Doxorubicin (DXR), administered iv in rats at the weekly dose of 3 mg/kg for 5 weeks, significantly impaired body weight gain and induced irreversible ECG alterations, mainly consisting of a progressive prolongation of ST and QT intervals. Five weeks after the last DXR administration, the contractile performance of atria isolated from treated animals was significantly reduced. At the same time, relevant morphologic lesions, consisting of myocyte vacuolization and myofibrillar loss, were also present in the myocardium of the same rats. The study showed that ICRF-187, administered ip at a dose of 125 mg/kg, significantly prevented body weight loss. QT and ST prolongation, and the decreased contractile force induced by DXR. In addition, ICRF-187 caused a significant reduction in incidence and severity of myocardial lesions. The cardioprotective effect of ICRF-187 is not mediated by a modification in DXR pharmacokinetics in heart, since the drug was actually found to increase DXR uptake in myocardial cells.