Overview of procalcitonin in pregnancy and in pre-eclampsia.

Procalcitonin (PCT), a precursor for calcitonin, is a prohormone involved in the inflammatory processes, which has been poorly studied in the context of pregnancy. During severe inflammation, PCT derives from almost all cell types, including monocytes and parenchymal tissues, making it a good predictive and diagnostic marker of an inflammatory state with rapidly increased serum levels in inflammation or sepsis. In normal pregnancy, PCT is basally expressed at very low level by decidual cells, even if decidual macrophages, which in normal pregnancy are skewed to M2 macrophages, are resistant to lipopolysaccharide (LPS)-induced production of PCT. As PCT increase is associated with an inflammatory state, several research groups investigated whether PCT can be considered a marker of pre-eclampsia, a pregnancy disease characterized by systemic inflammation. The first aim of this review is to summarize what is already known about the tissues synthesizing PCT, about the stimuli that cause the increase of circulating PCT levels and how PCT acts as a proinflammatory stimulus by itself. Secondly, we will describe the role of this prohormone in normal pregnancy and in pregnancies complicated by pre-eclampsia, highlighting the involvement of the decidual macrophages and the proinflammatory cytokine tumor necrosis factor-α in the modulation of PCT expression in the decidual microenvironment.

The combination of N-acetyl cysteine, alpha-lipoic acid, and bromelain shows high anti-inflammatory properties in novel in vivo and in vitro models of endometriosis.

To evaluate the efficacy of an association of N-acetyl cystein, alpha-lipoic acid, and bromelain (NAC/LA/Br) in the treatment of endometriosis we set up a new in vivo murine model. We explored the anti-inflammatory and proapoptotic effect of this combination on human endometriotic endothelial cells (EECs) and on endothelial cells isolated from normal uterus (UtMECs). We implanted fragments of human endometriotic cysts intraperitoneally into SCID mice to evaluate the efficacy of NAC/LA/Br treatment. UtMECs and EECs, untreated or treated with NAC/LA/Br, were activated with the proinflammatory stimulus TNF-α and their response in terms of VCAM1 expression was evaluated. The proapoptotic effect of higher doses of NAC/LA/Br on UtMECs and EECs was measured with a fluorogenic substrate for activated caspases 3 and 7. The preincubation of EECs with NAC/LA/Br prior to cell stimulation with TNF-α prevents the upregulation of the expression of the inflammatory "marker" VCAM1. Furthermore NAC/LA/Br were able to induce EEC, but not UtMEC, apoptosis. Finally, the novel mouse model allowed us to demonstrate that mice treated with NAC/LA/Br presented a lower number of cysts, smaller in size, compared to untreated mice. Our findings suggest that these dietary supplements may have potential therapeutic uses in the treatment of chronic inflammatory diseases like endometriosis.

Superficial siderosis of the CNS: MR diagnosis and clinical findings.

PURPOSE: To report the clinical and neuroradiologic findings of superficial siderosis of the CNS, due to chronic subarachnoid bleeding of unknown origin. MATERIALS AND METHODS: We observed seven cases. The main clinical manifestations were progressive deafness and ataxia. Four patients had had previous cranial or cervical trauma, with root avulsion in two, many years before onset of deafness and ataxia. Neuroradiologic studies included MR (0.5 T in four and 1.5 T in three) and angiography of the brain in all cases, CT in six cases, MR of the spine in six, and myelography in four. RESULTS: MR demonstrated a rim of marked hypointensity in T2-weighted images, consistent with hemosiderin deposits, on the surface of cerebellum, brain stem, inferior part of cerebral hemispheres, and spinal cord. CT showed cerebellar atrophy in five cases, and a rim of mild hyperdensity around the brain stem in two. Angiographic studies were negative. Myelography showed cervical nerve root avulsion in two cases and a cervicodorsal extradural cyst in one. Cerebrospinal fluid contained RBCs in all the six examined cases. CONCLUSION: Although CT may occasionally suggest the diagnosis of superficial siderosis, MR demonstrates this abnormality to better advantage.

Superficial siderosis of the central nervous system after brachial plexus injury. Case report.

Superficial siderosis is a rare condition characterized by deposition of hemosiderin in the leptomeninges and in the subpial layers of the brain and spinal cord. It is associated with cerebrospinal fluid abnormalities consistent with recurrent bleeding into the subarachnoid space. The usual symptoms are hearing loss, ataxia, spastic paraparesis, sensory and sphincter deficits, and mental deterioration. A case is presented of severe superficial siderosis of the central nervous system in a 51-year-old man who had suffered a brachial plexus injury at the age of 20 years. The diagnosis was made by means of magnetic resonance imaging 16 years after the initial symptoms, which comprised bilateral hearing loss and anosmia. Subarachnoid bleeding was due to traumatic pseudomeningocele of the brachial plexus, a very unusual cause of superficial siderosis. This case is interesting insofar as the surgical treatment prevented further bleeding and possibly progression of the disease.

Immunomodulation mediated by a herbal syrup containing a standardized Echinacea root extract: a pilot study in healthy human subjects on cytokine gene expression.

In this study, the immunomodulatory effect of a triply standardized Echinacea angustifolia root extract (Polinacea(®)) was evaluated in 10 healthy subjects. Ten ml of syrup containing one hundred mg of extract (corresponding to 4.7 mg of Echinacoside and 8.0mg of a high molecular weight-20,000 Da- polysaccharide) were administered as a herbal syrup once a day for one month. The immunomodulatory effect was evaluated before and after herbal syrup administration evaluating the expression levels of the cytokines IL-2, IL-8, IL-6 and TNF-α. Cytokine expression was studied in lympho-monocytes and in plasma samples measuring the mRNA and protein levels, respectively. The results were analysed by ANOVA and non-parametric Friedman rank sum tests; when possible it was adopted a pair-wise comparisons at different post-treatment times, using the paired t-tests with Holm correction. The correlation between the variations of cytokine plasma levels and the respective mRNA was carried out using a linear regression model. In lympho-monocytes our data indicate the up-regulation of the mRNA levels of IL-2 and IL-8 and the down regulation of the mRNA levels of the pro-inflammatory cytokines TNF-α and IL6. The differential regulation was maximal after 14 days of treatment. IL-2 up-regulation and IL-6 down-regulation were also confirmed at the protein level in plasma. Finally, the up-regulation of the mRNA of IL-2/IL-8 and the down-regulation of IL-6 positively correlated with the protein levels detected in the plasma. In conclusion, this pilot study suggests a relevant role for the standardized Echinacea angustifolia root extract in the control of cytokine expression. This first demonstration of the immuno-modulating activity of Echinacea angustifolia root extract in the healthy subject, supports at least in part the common use of such products as health promoting supplement.

Bacterial LPS differently modulates inflammasome gene expression and IL-1ß secretion in trophoblast cells, decidual stromal cells, and decidual endothelial cells.

Three Nod-like receptors (NLR family, pyrin domain containing 1/NLRP1, NLR family, pyrin domain containing 3/NLRP3, NLR family, CARD domain containing 4/NLRC4) and the adaptor molecule PYD and CARD domain containing protein/PYCARD are involved in the assembling of multiprotein complexes known as inflammasomes, leading to caspase 1 activation and consequent interleukin (IL)-1ß secretion. Considering that inflammasomes are involved in sensing pathogens and in triggering inflammatory and immune response, we hypothesized that they could also act in the placenta as an efficient innate mechanism during pregnancy infections. For this reason the activation of inflammasome was tested in 3 human placental cell populations in the presence of a common gram-negative compound (lipopolysaccharide [LPS]). The transcription of NLRP1, NLRP3, NLRC4, PYCARD, CASP1, and IL1B genes and the secretion of IL-1ß were evaluated in human first trimester cytotrophoblasts (CTBs), decidual stromal cells (DSCs), and endothelial cells (DECs) stimulated with LPS. In CTBs and DSCs, LPS induced an augmented expression of CASP1 and IL1B and the specific upregulation of NLRP3 within the 3 NLRs tested. Moreover, LPS induced secretion of IL-1ß from CTBs and DSCs. These results suggest the involvement of NLRP3 inflammasome in the placental innate response. The LPS did not affect inflammasome gene transcription and IL-1ß production in DECs. Bacterial LPS enhances NLRP3 inflammasome components in trophoblast and DSCs, suggesting that this innate immune complex could play a key role in placental immune defense.

Mannose-binding lectin is produced by vaginal epithelial cells and its level in the vaginal fluid is influenced by progesterone.

Mannose-binding lectin (MBL) is a recognition molecule of the complement (C) system and binds to carbohydrate ligands present on a wide range of pathogenic bacteria, viruses, fungi, and parasites. MBL has been detected in the cervico-vaginal cavity where it can provide a first-line defence against infectious agents colonizing the lower tract of the reproductive system. Analysis of the cervico-vaginal lavage (CVL) obtained from 11 normal cycling women at different phases of the menstrual cycle revealed increased levels of MBL in the secretive phase. Part of this MBL derives from the circulation as indicated by the presence of transferrin in CVL tested as a marker of vascular and tissue permeability. The local synthesis of MBL is suggested by the finding that its level is substantially higher than that of transferrin in the secretive phase. The contribution of endometrium is negligible since the MBL level did not change before and after hysterectomy. RT-PCR and in situ RT-PCR analysis showed that the vaginal tissue, and in particular the basal layer of the epithelium, is a source of MBL which binds to the basal membrane and to cells of the outer layers of the epithelium. In conclusion, we have shown that MBL detected in CVL derives both from plasma as result of transudation and from local synthesis and its level is progesterone dependent increasing in the secretive phase of the menstrual cycle.

Hiperparatiroidismo secundario a adenoma paratiroideo mediastinal / Hyperparathyroidism due to mediastinal parathyroid adenoma

Las glándulas paratiroides se localizan en el cuello, en la cara posterior de la glándula tiroides. Tienen como función secretar PTH, la cual está regulada por la concentración extracelular de calcio. Se define como hiperparatiroidismo a la producción excesiva de PTH por las glándulas paratiroideas, siendo el 85 % aproximadamente de los casos producto de un adenoma; un 12 % debido a hiperplasia y menos del 1 % por carcinomas. El hiperparatiroidismo primario ectápico se presenta en el 10 % de los pacientes, de los cuales del 1 al 2 % corresponde a la localización mediastinal(1). Presentamos una paciente de 38 años, internada en nuestra institución por hipercalcemia sintomática, comprobándose niveles plasmáticos elevados de PTH. Se le realizá una gammagrafía con tecnecio 99 MIBI que evidenció una imagen hipercaptante a nivel de mediastino anterior. Fue intervenida quirúrgicamente, obteniendo como resultado de la anatomía patolágica un adenoma paratiroideo.

The parathyroid glands are located in the neck, on the back of the thyroid gland. Their function is to secrete PTH, which is regulated by extracellular calcium concentration. Hyperparathyroidism is defined as the excessive production of PTH by the parathyroid glands; approximately 85 % of the cases are caused by an adenoma, 12 % due to hyperplasia and less than 1 % by carcinomas. Ectopic Primary hyperparathyroidism occurs in 10 % of the patients, of which from 1 to 2 % are of mediastinal location(1). We report the case of a 38-year-old patient hospitalized in our institution for symptomatic hypercalcemia. During her hospitalization elevated plasma levéis of PTH were found with image MIBI technetium 99 high uptake in the anterior mediastinum. She underwent surgery, and the pathology report showed parathyroid adenoma.

Large demyelinating brain lesion mimicking a herniating tumor.

We describe the case of a large brain lesion whose computed tomography appearance and clinical evolution mimicked a herniating tumor. The patient progressed to coma within 6 days of hospitalization despite high-dose steroid treatment. Emergency excision of the lesion was carried out. Histological analysis showed massive demyelination, axon preservation and no tumor cells. No lesion recurrence was seen during a 55-month follow-up. Recognition of such lesions through magnetic resonance imaging or spectroscopy may spare unnecessary surgery or biopsy. However, our case shows that such lesions may still require resection in the face of a rapid clinical progression and poor response to medical treatment.

Hemimegalencephaly in hypomelanosis of Ito: early sonographic pattern and peculiar MR findings in a newborn.

Sonography is a reliable tool for the evaluation of the most severe congenital abnormalities of the brain; in the present case it provided an early demonstration of hemimegalencephaly in hypomelanosis of Ito in a newborn affected by body hemihypertrophy and skin lesions. Serial magnetic resonance (MR) examinations confirmed the asymmetry of the cerebral hemispheres, and documented the evolution of the hemispheric growth and the presence of unusual aspects.

Spontaneous dissection of carotid and coronary arteries.

The authors report a case of spontaneous dissection of both carotid arteries, followed by spontaneous dissection of the left anterior descending coronary artery after a few days. No major abnormalities of collagen production were found. This case may be underlain by a dysplasia of common precursors of the carotid and coronary walls.

Dementia after first stroke.

BACKGROUND AND PURPOSE: Cognitive deficits may significantly worsen the quality of life after stroke. Our aim was to determine the frequency of dementia in a consecutive series of previously nondemented patients between the ages of 40 and 79 years at 3 months after a first ischemic stroke. METHODS: All patients admitted to our department during an 18-month period who met the above criteria were visited and tested and underwent a CT scan 3 months after their stroke. Dementia was diagnosed according to criteria of the National Institute of Neurological Disorders and Stroke and AIREN, but cases with aphasia were not excluded. RESULTS: Of 304 patients admitted for stroke, 146 were eligible for study. Eleven refused to participate, 25 were dead at 3 months, and 110 were tested. Fifteen patients were demented (13.6%; 95% confidence interval [CI], 7.8% to 21.5%), and six had severe isolated aphasia, neglect, or memory deficit (5.4%). Excluding patients with aphasia, 5.0% of cases showed dementia (95% CI, 1.6% to 11.3%). The frequency of dementia was 24.6% (95% CI, 14.5% to 37.3%), considering only patients with supratentorial lesions and with residual deficits of elementary functions (paresis, sensory deficits) at the time of examination. Demented patients had significantly more diabetes (P<.029), atrial fibrillation (P=.032), aphasia at entry (P<.001), large middle cerebral artery infarctions (P=.001), and a more severe neurological deficit at entry (P=.003) and at 3 months (P=.001). At CT scan, demented patients had a larger mean volume of the recent lesion (P<.001) and more lesions in the frontal lobe (P=.041). An exploratory multivariate analysis selected age between 60 and 69 years (odds ratio [OR], 45.8; 95% CI, 2.9 to 726.0), diabetes (OR 59.4; 95% CI, 4.3 to 821.0), aphasia (OR, 14.8; 95% CI, 2.0 to 111.0), a large middle cerebral artery infarction (OR, 30.0; 95% CI, 2.7 to 334.0), and lesions of the frontal lobe (OR, 9.8; 95% CI, 1.3 to 72.8) as significant independent correlates of poststroke dementia. CONCLUSIONS: Dementia is relatively frequent after a clinical first stroke in persons younger than 80 years, and aphasia is very often associated with poststroke dementia. If aphasic patients are not considered, it may be necessary to screen a very large number of subjects to collect an adequate sample of demented cases.