Hypoalbuminemia in COVID-19: assessing the hypothesis for underlying pulmonary capillary leakage.

BACKGROUND: Since the first observations of patients with COVID-19, significant hypoalbuminaemia was detected. Its causes have not been investigated yet. OBJECTIVE: We hypothesized that pulmonary capillary leakage affects the severity of respiratory failure, causing a shift of fluids and proteins through the epithelial-endothelial barrier. METHODS: One hundred seventy-four COVID-19 patients with respiratory symptoms, 92 admitted to the intermediate medicine ward (IMW) and 82 to the intensive care unit (ICU) at Luigi Sacco Hospital in Milan, were studied. RESULTS: Baseline characteristics at admission were considered. Proteins, interleukin 8 (IL-8) and interleukin 10 (IL-10) in bronchoalveolar lavage fluid (BALF) were analysed in 26 ICU patients. In addition, ten autopsy ultrastructural lung studies were performed in patients with COVID-19 and compared with postmortem findings in a control group (bacterial pneumonia-ARDS and H1N1-ARDS). ICU patients had lower serum albumin than IMW patients [20 (18-23) vs 28 (24-33) g L-1 , P < 0.001]. Serum albumin was lower in more compromised groups (lower PaO2 -to-FiO2 ratio and worst chest X-ray findings) and was associated with 30 days of probability of survival. Protein concentration was correlated with IL-8 and IL-10 levels in BALF. Electron microscopy examinations of eight out of ten COVID-19 lung tissues showed loosening of junctional complexes, quantitatively more pronounced than in controls, and direct viral infection of type 2 pneumocytes and endothelial cells. CONCLUSION: Hypoalbuminaemia may serve as severity marker of epithelial-endothelial damage in patients with COVID-19. There are clues that pulmonary capillary leak syndrome plays a key role in the pathogenesis of COVID-19 and might be a potential therapeutic target.

Liver infection and COVID-19: the electron microscopy proof and revision of the literature.

OBJECTIVE: COVID-19, the newly emerging infectious disease, has been associated with acute liver injury, often related to progression to severe pneumonia. The association between moderate-severe liver injury and more severe clinical course of COVID-19 has suggested that liver injury is prevalent in severe than in mild cases of COVID-19, while no difference in liver involvement has been reported between survivors and non-survivors. The spectrum of liver involvement during COVID-19 ranges from an asymptomatic elevation of liver enzymes to severe hepatitis. Only rarely, cases with acute hepatitis have been reported in the absence of respiratory symptoms. Both epithelial and biliary cells possess the angiotensin-converting enzyme-2 receptors that SARS-CoV-2 uses to be internalized. However, to our knowledge, no ultrastructural identification of the virus in liver cells has been reported to date. Here we provide evidence of SARS-CoV-2 in the liver of two patients, a 34-year-old woman and a 60-year-old man with COVID-19. PATIENTS AND METHODS: We investigated two patients with COVID-19 showing several virions within cytoplasmic vacuoles of cholangiocytes and in endothelial cells of hepatic sinusoids. In both patients, we performed histological and ultrastructural examinations by liver biopsy. After two months, both patients were free of symptoms, and the SARS-CoV-2 infection had resolved. RESULTS: Liver biopsy histological and ultrastructural examination showed liver injury and several virions within cytoplasmic vacuoles of cholangiocytes and in endothelial cells of hepatic sinusoids. CONCLUSIONS: Although most studies in COVID-19 have been focused on the lungs, recently, cholestatic liver pathology has been introduced in the spectrum of pathological changes related to COVID-19. To the best of our knowledge, those presented in this paper are the first images of hepatic SARS-CoV-2 infected liver cells. Our findings suggest a role for cholangiocytes and biliary structures in the COVID-19.

Glomerular lesions in HIV-positive patients: a 20-year biopsy experience from Northern Italy.

AIM: Glomerular involvement in HIV-positive patients is quite heterogeneous. In the present paper we reviewed 73 renal biopsies performed during a period of more than 20 years in a single Nephrology Unit, Milan, Northern Italy, in order to evaluate the aspects of single types of glomerular lesions (including HIV associated nephropathy-HIVAN), grouped according to histological patterns and clinical presentation. Moreover, in the group of non-HIVAN patients, the possible differences in histological characteristics from non-HIV lesions were investigated. MATERIALS AND METHODS: Renal tissues were obtained by percutaneous biopsies and were studied by light microscopy, immunofluorescence and electron microscopy. For the histological description three histological groups were identified: HIVAN, immune complex glomerulonephritis (GN) and glomerulopathies not related to immune-mediated mechanisms (so-called "various" glomerulopathies). RESULTS: HIVAN was observed in 9 cases, immune complex GNs in 40 cases (10 mesangial proliferative GN, 8 membranoproliferative GN, 5 lupus-like GN, 4 "acute" GN, 2 crescentic GN, 4 IgA nephropathy, 4 membranous GN and 3 immunotactoid GN) and "various" glomerulopathies in 24 cases (13 non-collapsing focal segmental glomerulosclerosis, 3 minimal changes, 3 end-stage renal disease, 4 diabetic nephropathy and one amyloidosis). CONCLUSIONS: Our 20-year biopsy series of HIV-related glomerular involvement confirmed the heterogeneity of lesions. In our series, the vast majority of HIV-related GN are the so-called immune complex GNs, with some peculiar aspects, as multiple site location of deposits and a frequent tendency towards sclerosis, in agreement with experimental data regarding HIV and fibrosis.

Inflammatory reaction and implantation: the new entries PTX3 and D6.

Successful embryonic implantation implies anchoring the conceptus in the maternal uterine wall, establishing a vascular supply to enable optimal growth and development of the conceptus, and promoting tolerance of fetal alloantigens encoded by paternal genes. To achieve these goals, complex molecular dialogues take place among the maternal endometrium, the conceptus, and the placenta. Several factors are involved in the fetal-maternal interaction, including hormones, growth factors, cytokines, chemokines, adhesion molecules, extracellular matrix components, and matrix-degrading enzymes. This complex cross-talk results in the induction of a local inflammatory response and a state of systemic inflammation, as revealed by leukocytosis, endothelium activation, increased activity of innate immune cells, and increased levels of inflammatory cytokines and chemokines. The enriched cytokine milieu associated to implantation is likely to control trophoblast migration and differentiation, leukocyte influx and activation, complement activation, as well as angiogenic and angiostatic processes in the implantation site. Finally, these mediators play a key role in tuning the immune responses to protect the fetus from infections as well as from maternal rejection. Here, the role of pro-inflammatory networks activated in implantation will be discussed. In particular, emphasis will be put on two new players involved in regulating inflammation at the maternal-fetal interface: the long pentraxin PTX3 and the decoy receptor for inflammatory chemokines D6.

Beta amyloid precursor protein and patterns of HIV p24 immunohistochemistry in different brain areas of AIDS patients.

OBJECTIVES: To evaluate the correlation between immunohistochemical positive patterns (globular and filamentous structures) of beta-amyloid precursor protein (beta-APP), used as a marker of axonal damage, and the different distribution of HIV p24 antigens, in three different brain areas of AIDS patients. METHODS: Eighteen AIDS patients with HIV-related brain lesions were included in the study. Forty-nine sections from basal ganglia, frontal cortex and hippocampus were selected. After microwave oven pre-treatment, the sections were incubated with anti-HIV p24 and anti-beta-APP monoclonal antibodies; the reactions were developed with peroxidase/3,3'diaminobenzidine. The positivity was graded by semi-quantitative scores. Double immunohistochemical staining was used to evaluate the co-localization of the antigens. RESULTS: HIV p24 immunohistochemistry was positive in 44 of 49 sections (89%), with a prevalence of interstitial positive cells and positive microglial nodules in 27 and 13 sections respectively. beta-APP-positive structures were demonstrated in 23 of 44 sections (52%) with HIV-related lesions, and were absent from the five sections without viral expression. Globular and filamentous lesions were observed in 21 of 23 sections and 10 of 23 lesions respectively. Moreover, a high grade of globular type lesion was related to an elevated presence of diffuse interstitial HIV p24-positive cells in basal ganglia; double immunohistochemical reactions demonstrated the co-localization of beta-APP globules and HIV p24 antigens. CONCLUSIONS: The data obtained confirm the coexpression of beta-APP and viral antigens in particular areas of the brain with HIV-related lesions; there is a strict correlation between beta-APP globules (indicating chronic cerebral damage) and the interstitial pattern of HIV p24 immunohistochemistry.

Predictors of cytomegalovirus disease, natural history and autopsy findings in a cohort of patients with AIDS.

OBJECTIVE: To identify the predictors of acquiring cytomegalovirus (CMV) disease, and to describe natural history, therapeutic management and autopsy findings in affected patients. DESIGN: Observational study of a consecutive cohort of AIDS patient diagnosed and followed in the same institution. METHODS: All of the patients with CMV were included. Statistical analyses were performed to establish the risk of acquiring the disease at or after AIDS presentation, survival, and the occurrence and time of relapses in relation to maintenance therapy. The presence of CMV infection at autopsy was also investigated. RESULTS: CMV disease was diagnosed in 304 (24.8%) out of 1,227 patients, its incidence increasing according to the year of AIDS diagnosis. Women, homosexual men, patients given zidovudine and Pneumocystis carinii pneumonia (PCP) prophylaxis before AIDS, and severely immunodepressed patients were at higher risk for the disease. CMV disease was an independent factor of worse survival (hazard ratio, 1.7 versus PCP; 95% confidence intervals, 1.28-2.13). Patients untreated during the acute phase had a 4.3 higher risk of dying than those treated. Relapses occurred less frequently and later in patients given continuous maintenance treatment (23 out of 113; 17 months) than in untreated patients (13 out of 16; 3 months) or those given discontinuous therapy (22 out of 40; 7 months), whereas survival was independent from treatment. CMV infection was found in 97 out of 134 patients at autopsy, but was unassociated with relapse. CONCLUSIONS: CMV is a severe disease whose frequency is higher in severely immunodepressed patients. Continuous treatment leads to a lower relapse rate even if it does not change survival or eradicate the infection.

Comprehensive study on structure-activity relationships of rifamycins: discussion of molecular and crystal structure and spectroscopic and thermochemical properties of rifamycin O.

The mechanism of action of rifamycins against bacterial DNA-dependent RNA polymerase has been explained on the basis of the spatial arrangement of four oxygens which can form hydrogen bonds with the enzyme. Structural descriptors are derived from X-ray diffraction crystal structures of 25 active and nonactive rifamycins. Principal component analysis is used to find the combination of structural parameters which better discriminate between active and nonactive rifamycins. Two possible mechanisms of molecular rearrangement are described which can convert nonactive into active conformations. The energy involved for conformational rearrangements is studied by molecular modeling techniques. Methyl C34 is found to play a key role for determining the geometry of the pharmacophore. Rifamycin O, reported to be active, is obtained by oxidation of rifamycin B and is studied by X-ray single-crystal diffractometry, by solution IR and NMR spectroscopy, and by thermal analysis. Surprisingly the oxidation process is totally stereospecific, and an explanation is given based on solution spectroscopic evidence. The conformation found in the solid state is typical of nonactive compounds, and molecular mechanics calculations show that a molecular rearrangement to the active conformation would require about 15 kcal/mol. Thermal analysis confirms that rifamycin O has a sterically constrained conformation. Therefore, it is likely that the antibiotic activity of rifamycin O is due either to chemical modification prior to reaching the enzyme or to conformational activation.

Nested polymerase chain reaction for Mycobacterium tuberculosis IS6110 sequence on formalin-fixed paraffin-embedded tissues with granulomatous diseases for rapid diagnosis of tuberculosis.

We evaluated the sensitivity and specificity of a nested polymerase chain reaction (PCR) to the Mycobacterium tuberculosis IS6110 sequence on formalin-fixed paraffin-embedded tissue samples from patients with tubercular and other granulomatous lesions. Five groups of patients and samples were studied: (1) 28 samples from HIV-positive patients with tuberculosis, (2) 8 samples from HIV-negative patients with histologically suspected tuberculosis (confirmed by culture in 5 cases), (3) lymph nodes from 5 HIV-positive patients with Mycobacterium avium-intracellulare infection, (4) lymph nodes from 30 patients with sarcoidosis, and (5) specimens from 17 patients with other granulomatous diseases. The DNA was extracted from sections with a total thickness of 60 microm, and PCR amplified an internal fragment of 123 base pairs. All of the cases with M. tuberculosis infection were PCR-positive, although this sensitivity was partially related to the initial concentration of the DNA used for amplification. Two of the group 4 samples also were repeatedly positive, thus reducing the specificity of the method. All of the cases with granulomatous diseases other than sarcoidosis were negative. We propose a simplified and highly sensitive nested PCR for the diagnosis of M. tuberculosis infection on archived material in HIV-positive and HIV-negative patients.

Molecular characterization and sequence analysis of polyomavirus strains isolated from needle biopsy specimens of kidney allograft recipients.

We retrospectively examined 29 renal allograft biopsy specimens from 42 kidney transplant recipients by means of molecular biologic techniques (nested polymerase chain reaction), immunohistochemical analysis (anti-SV40 antibody), and histologic examination to evaluate the presence of polyomaviruses (PVs), viral genotypes, genomic mutations, and their pathologic significance. PV genomes were found in six cases (21%); restriction fragment length polymorphism analysis characterized 4 as JC virus (JCV) and 2 as BK virus (BKV). The latter also were positively stained immunohistochemically and showed histologically typical intranuclear viral inclusions; JCV cases were negative. DNA sequence analysis revealed only minor changes in the 4 JCV cases (3 archetypes and 1 JCV type 3, not associated with a known pathogenic genotype) but identified 2 specific variants in the BKV isolates (AS and WW strains). Given the different histologic findings (mixed inflammatory infiltration in the AS and no inflammation in the WW strain), we speculate that different BKV strains may cause differential damage in transplanted kidneys. Finally, the negative histologic and immunohistochemical JCV results, as well as the absence of viral mutations, indicate that JCV renal infection is latent in transplant recipients.

Hepatic histology of patients with HIV infection and chronic hepatitis C treated with interferon.

AIMS: To evaluate the histological changes seen in liver biopsies after interferon (IFN) treatment in patients with chronic hepatitis C and human immunodeficiency virus (HIV) infection. METHODS: Twenty four intravenous drug users with chronic hepatitis C were investigated histologically before beginning a 12 month course of IFN treatment and 18 months later. Twelve were HIV positive, without opportunistic or other viral infections (group A), and 12 were HIV negative (group B). RESULTS: According to alanine amino-transferase concentrations, four sustained responders and eight non-responders were found in group A; six sustained responders, five relapsers, and one non-responder were found in group B. HCV RNA became negative in one sustained responder of group A and in the six sustained responders of group B. When histological findings of biopsies performed before therapy and 18 months later were compared, no significant changes in the mean value of Knodell's index and subindices were found in group A, whereas in group B Knodell's index, piecemeal necrosis, and focal hepatocellular necrosis decreased significantly. CONCLUSIONS: In chronic hepatitis C, coinfection with HIV showed a tendency towards a lower response to IFN, although this did not reach statistical significance; however, none of the HIV positive patients developed cirrhosis during the follow up and this should be considered in clinical management of such patients.

Renal Encephalitozoon (Septata) intestinalis infection in a patient with AIDS. Post-mortem identification by means of transmission electron microscopy and PCR.

We describe the occurrence of renal Encephalitozoon (Septata) intestinalis infection in a 35-year-old AIDS patient who died with disseminated tuberculosis. The patient did not complain of specific symptoms involving the kidney or lower urinary tract during life, but at autopsy, light microscopic examination of the kidney revealed numerous small round or oval bodies in the tubules and tubular cell cytoplasm that were interpreted as intracellular protozoa. Transmission electron microscopy of tissue retrieved from paraffin-embedded samples identified these organisms as microsporidia belonging to the Encephalitozoonidae family, but did not allow definitive identification of the species of infecting parasite. This was made possible only by means of Southern blot hybridization after the polymerase chain reaction, which recognized the micro-organism as E. intestinalis.

Extracellular matrix globules in renal oncocytoma.

Extracellular hyaline globules resulting from abnormal accumulation of matrix components have been described in several pathological conditions, including renal tumors. We studied 16 renal oncocytomas and observed these bodies in 11 of them. In these tumors, they showed a homogeneous texture as well as roundish, smooth contours, and were easily detected in hematoxylin-eosin sections in five cases. PAS staining greatly facilitated the identification of globules in the remaining six cases, where they were fewer in number. Immunohistochemically, they appeared to be composed primarily of basement membrane material, being strongly reactive to antibodies for type IV collagen, laminin, and heparan sulphate proteoglycan. In addition, a weak immunoreactivity for type I and type III collagen, and fibronectin was observed in some cases, whereas no globule stained for tenascin. We also analyzed 89 renal cell carcinomas, and found somewhat similar bodies in 10 of them. However, they were more scanty in the latter tumors, and displayed a more irregular configuration with granular or smudged contours. We conclude that, although the mere presence of extracellular hyaline globules does not justify a distinction between renal oncocytoma and renal cell carcinoma, the detection of a large number of well-demarcated, roundish extracellular bodies with smooth contours suggests renal oncocytoma.

Antibiotic GE2270 a: a novel inhibitor of bacterial protein synthesis. II. Structure elucidation.

GE2270 A, produced by Planobispora rosea ATCC 53773, inhibits Gram-positive bacteria and anaerobes by acting on the bacterial protein synthesis. The structure has been determined by physico-chemical methods applied to the intact molecule and to the main hydrolysis products. Characterization by UV, IR, NMR (double quantum filter COSY), acid-base ionization, elemental analysis and FAB-MS indicated that GE2270 A is a highly modified peptide having MW 1,289 and formula C56H55N15O10S6, and a weak basic function, and that it belongs to the thiazolyl peptide group of antibiotics. Acid hydrolysis yielded a main product (MW 634), responsible for the chromophoric absorption, and a number of hydrolyzed products of lower MW. 13C NMR inverse techniques and MS studies (EI, positive ion chemical ionization, and collision induced dissociation FAB-MS-MS experiments) on GE2270 A, the chromophoric compound, and the other hydrolysis products led to the complete identification of the various amino acid residues and their sequence. Two out of the six chiral centers have been determined. The structure is thought to originate from modification of a chain of 14 amino acids in a process which creates 6 thiazole rings and one pyridine. The modification process also closes the linear polypeptide to form a cyclic part with an attached side-chain. GE2270 A plausibly has a similar biosynthetic origin to that of other thiazolyl peptide antibiotics such as nosiheptide and micrococcin.

Rantes distribution and cellular localization in the brain of HIV-infected patients.

OBJECTIVE: To study the immunochemical distribution ofRantes chemokine and its correlation with HIV-p24 expression, in brains with HIV-related lesions. MATERIAL AND METHODS: 17 HIV-positive cases of HIV-related brain lesions, 7 HIV-positive cases without cerebral HIV-related lesions (5 with opportunistic brain diseases), and 7 HIV-negative cases as controls (4 with brain lesion) were selected. RESULTS: High expression of Rantes was observed in the cases with inflammatory brain lesions (22/24 HIV-positive and 2/7 HIV-negative patients). Positivity was observed in the diffuse and nodular microglial cells and lymphocytes. In the patients with HIV-related lesions, the presence of Rantes-stained microglia did not correlate with that of HIV-p24-positive cells. Positive astrocytes were only found in the HIV-positive patients. Multinucleated giant cells were always Rantes-negative. CONCLUSIONS: Our results seem to demonstrate the role of Rantes chemokine in inducing inflammatory brain perivascular and microglial reactions both in HIV-positive and -negative patients.

BK virus renal infection in a patient with the acquired immunodeficiency syndrome.

BACKGROUND: We describe herein a patient with the acquired immunodeficiency syndrome and renal failure due to biopsy-proven BK virus (BKV) infection. Three months after the diagnosis of the renal viral infection, his condition remained unchanged. Although BKV has previously been shown to be associated with ureteral stenosis and renal damage in renal transplant patients, to our knowledge, the literature contains only 3 cases describing the presence of BKV lesions in the kidneys of immunosuppressed patients who had not undergone transplantation. METHODS: The presence of BKV infection was demonstrated by means of histology, immunohistochemistry with polyclonal anti-SV40 antibody, immunoelectron microscopy, polymerase chain reaction, and enzymatic cleavage with BamHI. RESULTS: Histologic examination revealed interstitial inflammatory infiltrates and tubules with enlarged and eosinophilic nuclei. CONCLUSIONS: The high frequency of latent BKV infection and its reactivation during immunosuppression suggest that the possibility of its involvement in renal damage should be considered in immunocompromised patients.

Hepatic metastases from medullary thyroid carcinoma appearing twelve years after the eradication of primitive tumor: cytological and radiological aspects.

We report on radiological and cytological findings from a case of medullary thyroid carcinoma (MTC) metastatizing to the liver 12 yr after the eradication of the primary neoplasm. This behavior has never before been described in a sporadic form of MTC.

Cytologic and biomolecular diagnosis of polyomavirus infection in urine specimens of HIV-positive patients.

OBJECTIVE: To evaluate the frequency of human polyomavirus reactivation in urine specimens from HIV-positive patients; compare the sensitivity of cytology, immunohistochemistry and molecular biology; differentiate viral genotypes; and correlate the results with urinary cytologic abnormalities. STUDY DESIGN: Urine specimens from 78 unselected HIV-positive patients were evaluated by means of cytology, immunohistochemistry and nested polymerase chain reaction (n-PCR) to evaluate the presence of polyomaviruses. Restriction fragment length polymorphism (RFLP) was carried out in positive cases in order to differentiate BK virus (BKV) from JC virus (JCV). CD4 cells and serum creatinine levels were evaluated as indices of immune status and renal function, respectively, whereas the presence of red blood cells was used as an index of urogenital damage. RESULTS: Cytologic evidence of polyomavirus infection was found in 17 samples and immunohistochemically confirmed in 9; another 6 cytologically negative cases were detected by means of immunohistochemistry. In all cases, only one or two cells showed typical viral inclusions or positive staining. n-PCR identified 44 positive samples, thus confirming all of the cytologically and immunohistochemically positive cases and detecting polyomavirus genome in a further 21. RFLP detected 39 JCV, 1 BKV and 4 JCV-BKV infections. No correlation was found between the presence or type of polyomavirus and immune status, but red blood cells were found more frequently in the positive than in the negative samples. Serum creatinine levels fell within the normal range in all cases. CONCLUSION: Molecular biology is the most sensitive tool for detecting polyomavirus urinary infection in HIV-positive patients and the only reliable method of differentiating JCV and BKV viral genotypes.

Evolution of renal pathology in Fabry disease.

UNLABELLED: Fabry disease is a rare lysosomal storage disorder which results from deficient activity of the enzyme alpha-galactosidase A. The resultant deposition and progressive accumulation of glycosphingolipids in all types of body tissue leads to severe clinical manifestations involving the heart, CNS and kidney. Renal manifestations are observed relatively early in the course of the disease, and progression to end-stage renal failure is common in hemizygous males in the third to fifth decades of life. Renal biopsy specimens reveal evidence of diffuse intracytoplasmic glycosphingolipid accumulation, mainly affecting podocytes and epithelial cells of distal tubules, which are strikingly enlarged and vacuolated. On electron microscopy the deposits appear as typical osmiophilic inclusion bodies in the cytoplasm of all kinds of renal cells, and show a characteristic 'onion skin' or 'zebra' appearance. These pathological features are also evident in heterozygous females. Deposits occur before the development of renal impairment. As patients age, the disease progresses in cells throughout the kidney, and is associated with increasing glycosphingolipid accumulation. CONCLUSION: The age-related evolution of renal pathology in Fabry disease is closely correlated with progressive intracellular deposition of glycosphingolipid and ultimately leads to end-stage renal failure.

[Thermoanalytic techniques for the study of pharmaceutical products]. / Tecnich termoanalitiche per lo studio di prodotti farmaceutici.

During the past years, there have been frequent demonstrations that thermoanalytical methods have found wide-spread use in pharmacy. Analysts have developed these techniques in pharmaceutical field in the estimation of impurities, in quality control procedures, in preformulation studies, in the active principle identification, in accelerated stability and in production process optimization. Wide-spread use of thermal methods is devoted to the identification of solid state of drugs (polymorphism, solvate, inclusion compound,...) due to its possible implication on bioavailability or on the stability of a final dosage form. Some examples of thermoanalytical applications are reported.

PTX3 as a potential endothelial dysfunction biomarker for severity of preeclampsia and IUGR.

Endothelial dysfunction typical of preeclampsia (PE) is the result of an excessive maternal inflammatory response to pregnancy. We investigated PTX3 in maternal, fetal and placental compartments in complicated pregnancies. Maternal blood samples were collected during the third trimester in 53 PE, 43 IUGR (intrauterine growth restriction) and 50 normal pregnancies. Fetal samples were collected from the umbilical vein in 26 PE, 23 IUGR and 26 normal pregnancies at elective cesarean section. Pattern and site of expression of PTX3 were studied by immunohistochemistry (IHC) on placenta, decidual bed and maternal peritoneum. PE and IUGR pregnancies had significantly higher maternal PTX3 levels compared to normal pregnancies, with IUGR significantly lower than PE. Maternal peritoneum expressed a significantly higher signal in the endothelium of pathological compared to normal pregnancies. The maternal increase of PTX3 correlated with the severity of disease with higher PTX3 concentrations in severe PE. Increased PTX3 levels in PE and IUGR mothers, together with IHC data represent the expression of altered endothelial function on the maternal side. IUGR fetuses had higher PTX3 values than controls and the increase was related to IUGR severity, likely reflecting the hypoxic environment. These data confirm the relevance of PTX3 in support the hypothesis that PE is a disease associated with altered maternal endothelial function. The PTX3 increase in IUGR fetuses deserves further investigation.