Increased hexosamine biosynthetic pathway flux alters cell-cell adhesion in INS-1E cells and murine islets.

PURPOSE: In type 2 Diabetes, ß-cell failure is caused by loss of cell mass, mostly by apoptosis, but also by simple dysfunction (dedifferentiation, decline of glucose-stimulated insulin secretion). Apoptosis and dysfunction are caused, at least in part, by glucotoxicity, in which increased flux of glucose in the hexosamine biosynthetic pathway plays a role. In this study, we sought to clarify whether increased hexosamine biosynthetic pathway flux affects another important aspect of ß-cell physiology, that is ß-cell-ß-cell homotypic interactions. METHODS: We used INS-1E cells and murine islets. The expression and cellular distribution of E-cadherin and ß-catenin was evaluated by immunofluorescence, immunohistochemistry and western blot. Cell-cell adhesion was examined by the hanging-drop aggregation assay, islet architecture by isolation and microscopic observation. RESULTS: E-cadherin expression was not changed by increased hexosamine biosynthetic pathway flux, however, there was a decrease of cell surface, and an increase in intracellular E-cadherin. Moreover, intracellular E-cadherin delocalized, at least in part, from the Golgi complex to the endoplasmic reticulum. Beta-catenin was found to parallel the E-cadherin redistribution, showing a dislocation from the plasmamembrane to the cytosol. These changes had as a phenotypic consequence a decreased ability of INS-1E to aggregate. Finally, in ex vivo experiments, glucosamine was able to alter islet structure and to decrease surface abundandance of E-cadherin and ß-catenin. CONCLUSION: Increased hexosamine biosynthetic pathway flux alters E-cadherin cellular localization both in INS-1E cells and murine islets and affects cell-cell adhesion and islet morphology. These changes are likely caused by alterations of E-cadherin function, highlighting a new potential target to counteract the consequences of glucotoxicity on ß-cells.

Inflammatory Response Modulation by Vitamin C in an MPTP Mouse Model of Parkinson's Disease.

Vitamin C (Vit C) is anutrient present in many foods, particularly citrus fruits, green vegetables, tomatoes, and potatoes. Vit C is studied for its applications in the prevention and management of different pathologies, including neurodegenerative diseases. Neuroinflammation is a defense mechanism activated by a stimulus or an insult that is aimed at the preservation of the brain by promoting tissue repair and removing cellular debris; however, persistent inflammatory responses are detrimental and may lead to the pathogenesis and progression of neurodegenerative diseases like Parkinson's disease (PD) and Alzheimer's disease. PD is one of the most common chronic progressive neurodegenerative disorders, and oxidative stress is one of the most important factors involved in its pathogenesis and progression.Due to this, research on antioxidant and anti-inflammatory compounds is an important target for counteracting neurodegenerative diseases, including PD. In the central nervous system, the presence of Vit C in the brain is higher than in other body districts, but why and how this occurs is still unknown. In this research, Vit C, with its anti-inflammatory and anti-oxidative properties, is studied to better understand its contribution to brain protection; in particular, we have investigated the neuroprotective effects of Vit C in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of PD and its role in the modulation of neuroinflammation. First, we observed that Vit C significantly decreased the MPTP-induced loss of tyrosine hydroxylase (TH)-positive dopaminergic neuronal cells in the substantia nigra, as well as microglial cell activation and astrogliosis. Furthermore, gait and spontaneous locomotor activity, evaluated by an automated treadmill and the Open Field test, respectively, were partially ameliorated by Vit C treatment in MPTP-intoxicated animals. In relation to neuroinflammation, results show that Vit C reduced the protein and mRNA expression of inflammatory cytokines such as IL-6, TLR4, TNF-α, iNOS, and CD40, while anti-inflammatory proteins such as IL-10, CD163, TGF-ß, and IL-4 increased. Interestingly, we show for the first time that Vit C reduces neuroinflammation by modulating microglial polarization and astrocyte activation. Moreover, Vit C was able to reduce NLRP3 activation, which is linked to the pathogenesis of many inflammatory diseases, including neuroinflammatory disorders. In conclusion, our study provides evidence that Vit C may represent a new promising dietary supplement for the prevention and alleviation of the inflammatory cascade of PD, thus contributing to neuroprotection.

Autism Spectrum Disorder and Prenatal or Early Life Exposure to Pesticides: A Short Review.

Background: Autism spectrum disorder (ASD) diagnoses have rapidly increased globally. Both environmental and genetic factors appear to contribute to the development of ASD. Several studies have shown a potential association between prenatal or postnatal pesticide exposure and the risk of developing ASD. Methods: We reviewed the available literature concerning the relationship between early life exposure to pesticides used in agriculture, such as organochlorines, organophosphates and pyrethroids, and ASD onset in childhood. We searched on Medline and Scopus for cohort or case-control studies published in English from 1977 to 2020. Results: A total of seven articles were selected for the review. We found a remarkable association between the maternal exposure to pyrethroid, as well as the exposure to organophosphate during pregnancy or in the first years of childhood, and the risk of ASD onset. This association was found to be less evident with organochlorine pesticides. Pregnancy seems to be the time when pesticide exposure appears to have the greatest impact on the onset of ASD in children. Conclusions: Among the different environmental pollutants, pesticides should be considered as emerging risk factors for ASD. The potential association identified between the exposure to pesticides and ASD needs to be implemented and confirmed by further epidemiological studies based on individual assessment both in outdoor and indoor conditions, including multiple confounding factors, and using statistical models that take into account single and multiple pesticide residues.

Formyl Peptide Receptor (FPR)1 Modulation by Resveratrol in an LPS-Induced Neuroinflammatory Animal Model.

Among therapeutic approaches that have been investigated, targeting of receptors implicated in managing neuroinflammation has been described. One such family of receptors comprises the formyl peptide receptors (FPRs) whose ligands could play a role in host defense. The murine FPR gene family includes at least six members while in humans there are only three. The two most important members are the Fpr1 and Fpr2. Fpr1encodes murine FPR1, which is considered the murine orthologue of human FPR. Resveratrol, a non-flavonoid polyphenol rich in red wine and grapes, apart from its beneficial health effects and anti-inflammatory properties, has been reported to reduce neuroinflammation in different neurodegenerative disease models. Resveratrol anti-inflammatory responses involve the activation of the protein deacetylase sirtuin 1 (SIRT1) gene. In this work we have investigated in an LPS-based murine model of neuroinflammation the role of FPR1, examining not only if this receptor undergoes a reduction of its expression during neuroinflammation, but also whether treatment with resveratrol was able to modulate its expression leading to an amelioration of neuroinflammatory picture in a murine model of neuroinflammation. Results of this work showed that FPR1 together with SIRT1 resulted upregulated by resveratrol treatment and that this increase is associated with an amelioration of the neuroinflammatory picture, as demonstrated by the induction of IL-10 and IL1-RA expression and the downregulation of proinflammatory mediators, such as TNF-α and IL-1ß. The expression and the modulation of FPR1 by resveratrol may be evaluated in order to propose a novel anti-inflammatory and pro-resolving therapeutic approach for the reduction of the detrimental effects associated with neuro-inflammation based neurodegenerative diseases and also as a promising strategy to promote human health by a diet rich in antioxidative bioactive compounds.

A specific lipid metabolic profile is associated with the epithelial mesenchymal transition program.

Several studies have identified a specific metabolic program that is associated with the process of epithelial-mesenchymal transition (EMT). Whereas much is known about the association between glucose metabolism and EMT, the contribution of lipid metabolism is not still completely understood. Here, we studied epithelial and mesenchymal breast cancer cells by proteomic and lipidomic approaches and identified significant differences that characterised these models concerning specific metabolic enzymes and metabolites including fatty acids and phospholipids. Higher levels of monounsaturated fatty acids together with increased expression of enzymes of de novo fatty acid synthesis is the distinct signature of epithelial with respect to mesenchymal cells that, on the contrary, show reduced lipogenesis, higher polyunsaturated fatty acids level and increased expression of genes involved in the triacylglycerol (TAG) synthesis and lipid droplets formation. In the mesenchymal model, the diacylglycerol acyltransferase (DGAT)-1 appears to be the major enzyme involved in TAG synthesis and inhibition of DGAT1, but not DGAT2, drastically reduces the incorporation of labeled palmitate into TAG. Moreover, knockdown of ß-catenin demonstrated that this metabolic phenotype in under the control of a network of transcriptional factors and that ß-catenin has a specific role in the regulation of lipid metabolism in mesenchymal cells.

Potential Role of OERP as Early Marker of Mild Cognitive Impairment.

Olfactory impairment is present in up to 90% of patients with Alzheimer's disease (AD) and is present in certain cases of mild cognitive impairment (MCI), a transient phase between normal aging and dementia. Subjects affected by MCI have a higher risk of developing dementia compared to the general population, and studies have found that olfactory deficits could be an indicator of whether such a conversion might happen. Following these assumptions, aim of this study was to investigate olfactory perception in MCI patients. We recruited 12 MCI subjects (mean age 70 ± 6.7 years) through the Alzheimer Assessment Unit (UVA Unite) of ASL Lecce (Italy), and 12 healthy geriatric volunteers (HS) as the control group (mean age 64 ± 6.0 years), all of whom were first evaluated via a panel of neuropsychological tests. Subjects were asked to perform an olfactory recognition task involving two scents: rose and eucalyptus, administrated in the context of an oddball task during EEG recordings. Olfactory event-related potential (OERP) components N1 and Late Positive Potential (LPC) were then analyzed as measures of the sensorial and perceptive aspects of the olfactory response, respectively. It was determined that, in the MCI group, both the N1 and LPC components were significantly different compared to those of the HS group during the execution of the oddball task. In particular, the N1 amplitude, was reduced, while the LPC amplitude was increased, indicating that a degree of perceptive compensation can occur when sensorial function is impaired. Further, a correlation analysis, involving OERP components and neuropsychological battery scores, indicated that impairment of olfactory perception may share common pathways with impairments of the spatial system and long-term memory processing.

Radio Electric Asymmetric Conveyer Technology Modulates Neuroinflammation in a Mouse Model of Neurodegeneration.

In this study, the effects of Radio Electric Asymmetric Conveyer (REAC), a non-invasive physical treatment, on neuroinflammatory responses in a mouse model of parkinsonism induced by intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were investigated in vivo. We found that the REAC tissue optimization treatment specific for neuro-regenerative purposes (REAC TO-RGN-N) attenuated the inflammatory picture evoked by MPTP-induced nigro-striatal damage in mice, decreasing the levels of pro-inflammatory molecules and increasing anti-inflammatory mediators. Besides, there was a significant reduction of both astrocyte and microglial activation in MPTP-treated mice exposed to REAC TO-RGN-N. These results indicated that REAC TO-RGN-N treatment modulates the pro-inflammatory responses and reduces neuronal damage in MPTP-induced parkinsonism.

Highly Selective Cyclooxygenase-1 Inhibitors P6 and Mofezolac Counteract Inflammatory State both In Vitro and In Vivo Models of Neuroinflammation.

Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose accumulation contributes to neuronal damages. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2), which play a critical role in the inflammation, are the pharmacological targets of non-steroidal anti-inflammatory drugs, used to treat pain and inflammation. Since it was reported that COX-1 is the major player in mediating the brain inflammatory response, the aim of this study was to evaluate the effects of highly selective COX-1 inhibitors, such as P6 and mofezolac, in neuroinflammation models. Lipopolysaccharide (LPS)-activated mouse BV-2 microglial cells and LPS intracerebroventricular-injected mice as in vitro and in vivo neuroinflammation models, respectively, were used to probe the antiinflammatory efficacy of P6 and mofezolac. Both P6 and mofezolac reduce COX-1 expression in LPS-activated BV-2 cells. This reduction was accompanied with PGE2 release reduction and NF-kB activation downregulation. Coextensively, in the in vivo model, both glial fibrillary acidic protein and ionized calcium-binding adapter molecule-1 expression, two markers of inflammation, were reduced by mofezolac to a rank depending on the encephalon area analyzed. The increase of COX-1 expression observed in all the brain sections of LPS-treated mice was selectively downregulated by the in vivo treatment with mofezolac as well as PGE2 release and Ikßα phosphorylation amount assayed in the brain areas tested. These results indicate the capability of P6 and mofezolac to modulate the NF-kB signaling pathway, emphasizing the neuroprotective effect and therapeutic potential of COX-1 inhibitors in the control of neuroinflammatory diseases.

Vitamin D Treatment Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in an Animal Model of Parkinson's Disease, Shifting M1 to M2 Microglia Responses.

Microglia-mediated neuroinflammation has been described as a common hallmark of Parkinson's disease (PD) and is believed to further exacerbate the progressive degeneration of dopaminergic neurons. Current therapies are unable to prevent the disease progression. A significant association has been demonstrated between PD and low levels of vitamin D in patients serum, and vitamin D supplement appears to have a beneficial clinical effect. Herein, we investigated whether vitamin D administered orally in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced preclinical animal model of PD protects against glia-mediated inflammation and nigrostriatal neurodegeneration. Vitamin D significantly attenuated the MPTP-induced loss of tyrosine hydrlase (TH)-positive neuronal cells, microglial cell activation (Iba1-immunoreactive), inducible nitric oxide synthase (iNOS) and TLR-4 expression, typical hallmarks of the pro-inflammatory (M1) activation of microglia. Additionally, Vitamin D was able to decrease pro-inflammatory cytokines mRNA expression in distinct brain areas of the MPTP mouse. Importantly, we also assessed the anti-inflammatory property of vitamin D in the MPTP mouse, in which it upregulated the anti-inflammatory cytokines (IL-10, IL-4 and TGF-ß) mRNA expression as well as increasing the expression of CD163, CD206 and CD204, typical hallmarks of alternative activation of microglia for anti-inflammatory signalling (M2). Collectively, these results demonstrate that vitamin D exhibits substantial neuroprotective effects in this PD animal model, by attenuating pro-inflammatory and up-regulating anti-inflammatory processes.

A rapid and simple method for the determination of 3,4-dihydroxyphenylacetic acid, norepinephrine, dopamine, and serotonin in mouse brain homogenate by HPLC with fluorimetric detection.

A fast and simple isocratic high-performance liquid chromatography method for the determination of 3,4-dihydroxyphenylacetic acid (DOPAC), norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in homogenate samples of mouse striatum employing the direct fluorescence of the neurotransmitters is described. The method has been optimized and validated. The analytes were separated in 15min on a reversed-phase column (C18) with acetate buffer (pH 4.0, 12mM)-methanol (86:14, v/v) as mobile phase; the flow rate was 1ml/min. The fluorescence measurements were carried out at 320nm with excitation at 279nm. The calibration curve for DA was linear up to about 2.5µg/ml, with a coefficient of determination (r(2)) of 0.9995 with a lower limit of quantification of 0.031µg/ml. Since the procedure does not involve sample pre-purification or derivatisation, the recovery ranged from 97% to 102% and relative standard deviation (RSD) was better than 2.9%, the use of the internal standard is not mandatory, further simplifying the method. Similar performance was obtained for the other analytes. As a result, thanks to its simplicity, rapidity and adequate working range, the method can be used for the determination of 3,4-dihydroxyphenylacetic acid, dopamine, norepinephrine and serotonin in animal tissues. An experimental 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson-like disease has been used to demonstrate the method is fit-for-purpose.

A combined ultrasound and histologic approach for analysis of uterine fibroid pseudocapsule thickness.

Authors investigated 75 patients with uterine myomas, appraising whether fibroid pseudocapsule (FP) thickness varies depending on fibroid location, by a prospective cohort trial (level of evidence II-2) settled in University-affiliated Hospitals. Uteri were scanned via bidimensional and power Doppler ultrasound (US) to map the fibroids and record the FP thickness, prior to hysterectomy for symptomatic uterine fibroids. After hysterectomy, FP specimens were sampled and analyzed by pathologists. Ultrasound and histology data were matched. Pseudocapsule thickness of 108 fibroids was measured: subserosal fibroids (SSFs), intramural fibroids (IMFs), and fibroids near the endometrial cavity (FEC). The FEC's pseudocapsules were considerably thicker than those of IMF and SSF measured by US and histology (P = .001). A clear cutoff existed between FEC pseudocapsule thickness and all other pseudocapsules, with significant differences observed at 2 mm (P = .001). Similarity between histological and US measurements was observed only with IMF pseudocapsules, whereas FEC or SSF showed significant differences. The pseudocapsule of fibroids is considerably thicker near the endometrial cavity when compared to those of both IMFs and SSFs. Since fibroids closest to the endometrial cavity are the most involved in fertility and infertility and FP is considerably thicker near the endometrial cavity, it is possible to hypothesize an involvement of FP of fibroid near the endometrium since FP contains many neuropeptides and neurotransmitters that are physiologically active, even if these data may take on a broader meaning in a study on a larger number of patients.

Transient covalent interactions of newly synthesized thyroglobulin with oxidoreductases of the endoplasmic reticulum.

Newly synthesized thyroglobulin (Tg), the thyroid prohormone, forms detectable high molecular weight mixed disulfide adducts: until now, only Tg "adduct B" was identified as primarily engaging the endoplasmic reticulum oxidoreductases ERp57 and protein disulfide isomerase. Here, we demonstrate that the faster migrating Tg adduct C primarily engages the CaBP1/P5 oxidoreductase, whereas the slower migrating Tg adduct A primarily engages ERp72. Upon siRNA-mediated knockdown of CaBP1/P5 or ERp72, adducts C or A, respectively, are decreased. Within the three Tg adduct bands that do not exhibit a precursor-product relationship, Tg exhibits distinct oxidation patterns. We present evidence suggesting that disulfide maturation occurs within Tg monomers engaged in each of the adduct bands. Moreover, the same Tg substrate molecules can form simultaneous mixed disulfides with both CaBP1/P5 and protein disulfide isomerase, although these are generally viewed as components of distinct oxidoreductase-chaperone protein complexes. Such substrate-oxidoreductase combinations offer Tg the potential for simultaneous oxidative maturation along different parallel tracks leading to the native state.

Neuroprotective effects of resveratrol in an MPTP mouse model of Parkinson's-like disease: possible role of SOCS-1 in reducing pro-inflammatory responses.

In the present study we used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model to analyze resveratrol neuroprotective effects. The MPTP-induced PD model is characterized by chronic inflammation, oxidative stress and loss of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). We observed that resveratrol treatment significantly reduced glial activation, decreasing the levels of IL-1ß, IL-6 and TNF-α, as well as their respective receptors in the SNpc of MPTP-treated mice, as demonstrated by Western blotting, RT-PCR and quantitative PCR analysis. This reduction is related to possible neuroprotection as we also observed that resveratrol administration limited the decline of tyrosine hydroxylase-immunoreactivity induced in the striatum and SNpc by MPTP injection. Consistent with these data, resveratrol treatment up-regulated the expression of the suppressor of cytokine signaling-1 (SOCS-1), supporting the hypothesis that resveratrol protects DA neurons of the SNpc against MPTP-induced cell loss by regulating inflammatory reactions, possibly through SOCS-1 induction.

The opioid neuropeptides in uterine fibroid pseudocapsules: a putative association with cervical integrity in human reproduction.

The myoma pseudocapsule (MP) is a fibro-vascular network rich of neurotransmitters, as a neurovascular bundle, surrounding fibroid and separating myoma from myometrium. We investigated the distribution of the opioid neuropeptides, as enkephalin (ENK) and oxytocin (OXT), in the nerve fibers within MP and their possible influence in human reproduction in 57 women. An histological and immunofluorescent staining of OXT and ENK was performed on nerve fibers of MP samples from the fundus, corpus and isthmian-cervical regions, with a successive morphometric quantification of OXT and ENK. None of the nerve fibers in the uterine fundus and corpus MPs contained ENK and the nerve fibers in the isthmian-cervical region demonstrated an ENK value of up to 94 ± 0.7 CU. A comparatively lower number of OXT-positive nerve fibers were found in the fundal MP (6.3 ± 0.8 CU). OXT-positive nerve fibers with OXT were marginally increased in corporal MP (15.0 ± 1.4 CU) and were substantially higher in the isthmian-cervical region MP (72.1 ± 5.1 CU) (p < 0.01). The distribution of OXY neurofibers showed a slight into the uterine corpus, while are highly present into the cervico-isthmic area, with influence on reproductive system and sexual disorders manifesting after surgical procedures on the cervix.

NT, NPY and PGP 9.5 presence in myomeytrium and in fibroid pseudocapsule and their possible impact on muscular physiology.

The uterine myoma pseudocapsule is a neurovascular bundle surrounding fibroid, containing neuropeptides, probably involved in uterine scar healing. We studied neurotensin (NT), neuropeptide tyrosine (NPY), and protein gene product 9.5 (PGP 9.5) nerve fibres in the pseudocapsule neurovascular bundle of intramural uterine fibroids on 67 no pregnant women by intracapsular myomectomy sparing the neurovascular bundle, sampling full thickness specimens of the pseudocapsule of uterine fibroids (PUF) and normal myometrium (NM) obtained from the fundus uteri (FU) and the uterine body (UB). The samples were sent for histological and immunofluorescent analyses and compared by morphometrical quantification. The Conventional Unit (C.U.) difference of NT, NPY, and PGP 9.5 nerve fibres was statistically analyzed. Our results showed that NT, NPY, and PGP 9.5 neurofibers are almost equally present in PUF as in NM of a no pregnant uterus. As all of these neuropeptides are present in the uterine muscle and can affect muscle contractility, uterine peristalsis and muscular healing. A myomectomy respecting the pseudocapsule neurofibers should facilitate smooth muscle scarring and promote restoration of normal uterine peristalsis with a possible positive influence on fertility.

Chronic obstructive pulmonary disease phenotype desaturator with hypoxic vascular remodelling and pulmonary hypertension obtained by cluster analysis.

Significant heterogeneity of clinical presentation and disease progression exists within chronic obstructive pulmonary disease (COPD). This article discusses and refines the concept of desaturator phenotypes in COPD with pulmonary hypertension (PH) obtained by cluster analysis and presents a pattern of phenotypic markers that could be used as a framework for future diagnosis and research. Nocturnal oxygen desaturation results in sleep disturbances which predispose to nocturnal cardiac dysrhythmias, PH and possibly nocturnal death, particularly during acute exacerbations. We assume that in patients with COPD at least two factors play a role in PH: the severity of pulmonary impairment, and the severity of systemic nocturnal hypoxaemia due to reduced pulmonary functions. Establishing a common language for future research will facilitate our understanding and management of such a disease. This knowledge could lead to different pharmacological treatments and other interventions directed at specific phenotypic groups.

Ultrasound evaluation of uterine healing after laparoscopic intracapsular myomectomy: an observational study.

STUDY QUESTION: Can uterine scar healing after laparoscopic intracapsular myomectomy (LIM) be adequately monitored by traditional two-dimensional (2D) ultrasound (US) and Doppler velocimetry? SUMMARY ANSWER: The myometrial area of the scar after LIM can be followed by 2D US and Doppler velocimetry. WHAT IS KNOWN ALREADY: Apart from post-surgical adhesions, the main concern linked to laparoscopic myomectomy is the quality of healing of the myometrial incision: it has been suggested that US could be useful for assessing uterine scars after myomectomy. However, no diagnostic method has yet been widely accepted to assess the healing process. STUDY DESIGN, SIZE, DURATION: A cohort prospective study (level of evidence II-2), run in University-affiliated hospitals: 149 women with symptomatic uterine fibroids (UFs) underwent LIM, between January 2007 and October 2011. During follow up 13 patients withdrew from the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: After LIM, all patients were followed by traditional 2D US scanning and Doppler velocimetry on Days: 0, 1, 7, 30 and 45. Authors evaluated: number, size and location of UFs, scar diameter and Doppler velocimetry and resistance index (RI) of the uterine arteries, at their ascending branch. MAIN RESULTS AND THE ROLE OF CHANCE: The uterine examination showed a significant (P < 0.05) progressive reduction of uterine scar area from 78% of the previous UF location on the first day, to 19% on 30th day, and <4% on the 45th day. There was no correlation with the size of the fibroid or the relative reduction in the size of the scar, on both Days 1 and 45. There was a significant (P < 0.05) increase in the RI of the ipsilateral uterine arteries from 0.65 on the first post-operative day to 0.83 after 7 days followed by a decrease to 0.71 on the 30th and 0.61 on the 45th post-operative day. LIMITATIONS, REASONS FOR CAUTION: This is a cohort investigation on a limited number of patients and it does not surgically compare LIM and 'classic' myomectomy in the scar US follow up. WIDER IMPLICATIONS OF THE FINDINGS: LIM avoided intraoperative bleeding and excessive tissue damage, as post-operative US follow up showed, with just two intra-myometrial hematomas (1.5%). The 2D US and Doppler velocimetry, a non-invasive safe method to check the myometrium after LIM, can detect post-operative hematoma and disechogenic, heterogeneous or ill-defined scar area, all unfavorable signs for myometrial scarring. Moreover, Doppler transvaginal monitoring, evaluating the pulsatility index (PI) and RI of the uterine arteries at their ascending branch, could identify patients with altered PI and RI parameters, possible markers of impaired wound healing.

Uterine fibroid pseudocapsule studied by transmission electron microscopy.

OBJECTIVE: The fibroid pseudocapsule is a structure which surrounds the uterine fibroid, separates it from the uterine tissue and contains a vascular network rich in neurotransmitters like a neurovascular bundle. The authors examined the composition of the fibroid pseudocapsule using electron microscopy. STUDY DESIGN: Twenty non-pregnant patients were submitted to laparoscopic myomectomy by the intracapsular method and samples of the removed pseudocapsules were analyzed using transmission electron microscopy. RESULTS: At the ultrastructural level the pseudocapsule cells have the features of smooth muscle cells similar to the myometrium. So, the pseudocapsules are part of the myometrium which compresses the leiomyoma. CONCLUSION: This ultrastructural feature suggests that when removing fibroids their pseudocapsules should be preserved. This study confirms preliminary evidence that pseudocapsules contain neuropeptides together with their related fibers, as a neurovascular bundle. The surgeon's behavior should be directed to carefully control and spare this muscular surrounding tissue during fibroid excision, in order to preserve the myometrium as much as possible.

Use of cluster analysis to describe desaturator phenotypes in COPD: correlations between pulmonary function tests and nocturnal oxygen desaturation.

BACKGROUND: Significant heterogeneity of clinical presentation and disease progression exists within chronic obstructive pulmonary disease (COPD). Although forced expiratory volume in 1 second (FEV(1)) inadequately describes this heterogeneity, a clear alternative has not emerged. This article discusses and refines the concept of phenotyping desaturators in COPD and shows a possible pattern which could be used as a framework for future research. RECENT FINDINGS: COPD is a complex condition with pulmonary and extrapulmonary manifestations. We suggest that COPD phenotypes should be associated with clinically meaningful outcomes. The innovation of COPD phenotyping is defined as COPD desaturators. Sleep-related hypoxemia and hypercapnia are well recognized in COPD and the development of systemic inflammation during sleep. These sleep-related changes predispose to nocturnal cardiac arrhythmias, pulmonary hypertension, and possibly death, particularly during acute exacerbations. CONCLUSION: A more focused definition makes possible a classification of patients into two distinct subgroups for both clinical and research purposes. Establishing a common language for future research will facilitate our understanding and management of such diseases. Even if different treatment strategies have different outcomes for these groups, we will have confirmation, or otherwise, of the clinical value of cluster analysis. This knowledge could lead to pharmacological treatment and other interventions directed to specific phenotypic groups.

Effects of nCPAP therapy on cardiorespiratory outcomes in obstructive sleep apnea syndrome: compliance and technological advancements.

Obstructive sleep apnea syndrome (OSAS) is an independent and modifiable risk factor for cardiovascular diseases; however, the pathophysiological mechanisms underlying this association are not yet fully understood. Intermittent hypoxemia, one of the physiological markers of OSAS, is characterized by transient periods of oxygen desaturation followed by reoxygenation. The hypoxia-reoxygenation cycles are associated with oxidative stress that, in turn, triggers the activation of pathways that lead to cardiovascular damage. The results of several studies show that OSAS causes oxidative stress and that nasal continuous positive airway pressure therapy normalizes these biological abnormalities. In conclusion, treatment of OSAS with continuous positive airway pressure may lower cardiovascular risk by reducing sympathetic nerve activity, ambulatory blood pressure and arterial stiffness, and by increasing sensitivity of the arterial baroreflex. Newer modalities such as C-Flex and A-Flex also show promise as treatment options in the future. However, the evidence supporting the use of these alternative modalities remains scant, in particular with regards to long-term cardiovascular outcomes.