<Emphasis Type="Italic">Helicobacter bilis</Emphasis>-Associated Suppurative Cholangitis in a Patient with X-Linked Agammaglobulinemia

?

Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases.

Purpose

We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis.

Methods

16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis.

Results

Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin.

Conclusion

In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.

     

<Emphasis Type="Italic">Terminalia bellirica</Emphasis> fruit extracts: in-vitro antibacterial activity against selected multidrug-resistant bacteria,radical scavenging activity and cytotoxicity study on BHK-21 cells

Background

Identification of novel sources for developing new antibiotics is imperative with the emergence of antibiotic resistant bacteria. The fruits of Terminalia bellirica (Gaertn) Roxb., widely used in traditional medicine, were evaluated for antibacterial activity against multidrug-resistant (MDR) bacteria, antioxidant activity and cytotoxicity.

Methods

Twelve solvent extracts of T. bellirica fruits were prepared by direct aqueous extraction and sequential extraction with dichloromethane, methanol and water using Soxhlet, bottle-shaker and ultrasound sonicator methods. Antibacterial activity of the extracts was tested against 16 strains MDR bacteria—methicillin-resistant Staphylococcus aureus (MRSA), extended spectrum β-lactamase (ESBL) producing Escherichia coli and MDR Acinetobacter spp., Klebsiella pneumoniae and Pseudomonas aeruginosa—and 4 control organisms, using the cut-well diffusion method. The minimum inhibitory concentration (MIC) was determined using an agar dilution method. The radical scavenging activity of six antibacterial extracts was screened against 2,2′-diphenyl-2-picrylhydrazyl (DPPH) and correlation was established between EC₅₀ (50% effective concentration) values and the total phenolic content (TPC). Cytotoxicity was determined for the most potent antibacterial extract on baby hamster kidney (BHK-21) cells by Tryphan Blue exclusion method. Statistical analysis was carried out by one-way analysis of variance at significant level p?<?0.05 using “SigmaPlot 10” and “R 3.2.0” software.

Results

All aqueous and methanol extracts displayed antibacterial activity (MIC 0.25–4?mg/mL) against all strains of MRSA, MDR Acinetobacter spp. and MDR P. aeruginosa. The sequential aqueous extracts (MIC, 4?mg/mL) inhibited ESBL producing-E. coli. None of the extracts exhibited activity against MDR K. pneumoniae (MIC >?5?mg/mL). The sequential methanol extract (Soxhlet) recorded high antibacterial activity and the highest DPPH radical scavenging activity (EC₅₀, 6.99?±?0.15?ppm) and TPC content (188.71?±?2.12 GAE mg/g).The IC₅₀ (50% inhibition concentration) values of the most potent antibacterial extract—the direct aqueous extract from reflux method—on BHK-21 cells were 2.62?±?0.06 and 1.45?±?0.08?mg/ml with 24 and 48?h exposure, respectively.

Conclusions

Results indicate that T. bellirica fruit is a potential source for developing broad-spectrum antibacterial drugs against MDR bacteria, which are non-toxic to mammalian cells and impart health benefits by high antioxidant activity.

     

Estrogen-like activity of aqueous extract from <Emphasis Type="Italic">Agrimonia pilosa</Emphasis> Ledeb. in MCF-7 cells

Background

Postmenopausal women experience estrogen deficiency-related menopausal symptoms (e.g., hot flashes and mood swings) and a dramatic increase in the incidence of chronic diseases. Although estrogen-replacement therapy (ERT) can reduce mortality from cardiovascular disease and improve osteoporosis and menopausal symptoms, its side effects have limited recent use. This study investigated the estrogen-like activity of aqueous extract from Agrimonia pilosa Ledeb.

Methods

The estrogenic activity of A. pilosa was investigated by using several in vitro assays. The binding activity of A. pilosa on estrogen receptors was examined using a fluorescence polarization-based competitive binding assay. The proliferative activity of A. pilosa was also examined using MCF-7 cells. Furthermore, the effect of A. pilosa on the expression of 3 estrogen-dependent genes was assessed.

Results

Using liquid chromatography-mass spectrometry, the 3 major peaks of A. pilosa aqueous extract were identified as apigenin-hexose, luteolin-glucuronide, and apigenin-glucuronide. The aqueous extract induced the proliferation of estrogen receptor-positive MCF-7 cells (p?<?0.05). A. pilosa-stimulated proliferation was blocked on adding the estrogen antagonist ICI 182,780. Moreover, A. pilosa treatment increased the mRNA expression of the estrogen-responsive genes pS2 and PR (p?<?0.05).

Conclusions

These results suggest A. pilosa can be used to improve estrogen deficiency-related menopausal symptoms or to treat diseases in postmenopausal women.

     

Antidepressant-like effects of a water-soluble extract from the culture medium of <Emphasis Type="Italic">Ganoderma lucidum</Emphasis> mycelia in rats

Background

Ganoderma lucidum is a popular medicinal mushroom used for promoting health and longevity in Asian countries. Previously, we reported that a water-soluble extract from a culture medium of Ganoderma lucidum mycelia (MAK) exerts antioxidative and cerebroprotective effects against ischemia–reperfusion injury in vivo. Here, we evaluated the antidepressant and anxiolytic activities of MAK in rats.

Methods

MAK (0.3 or 1 g/kg, p.o.) was administered in the experimental animals 60 min before the forced swimming, open-field, elevated plus-maze, contextual fear-conditioning, and head twitch tests. Additionally, the mechanisms involved in the antidepressant-like action of MAK were investigated by the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP)- or 5-HT_2A agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI)-induced head twitch responses.

Results

Treatment with MAK (1 g/kg) exhibited antidepressant-like effects in the forced swimming test, attenuated freezing behavior in the contextual fear-conditioning test, and decreased the number of head twitches induced by DOI, but not with 5-HTP. No significant response was observed in locomotion or anxiety-like behavior, when the animals were evaluated in the open-field or elevated plus-maze test, respectively.

Conclusions

These data suggest that MAK has antidepressant-like potential, which is most likely due to the antagonism of 5-HT_2A receptors, and possesses anxiolytic-like effects toward memory-dependent and/or stress-induced anxiety in rats.

     

Antipyretic,anti-inflammatory and analgesic activity of <Emphasis Type="Italic">Acacia hydaspica</Emphasis> R. Parker and its phytochemical analysis

Background

Inflammation and pain underlies several pathological conditions. Synthetic drugs used for the management of these conditions carry severe toxic effects. Globally efforts are ongoing to introduce novel medicinal plants to develop effective, economic and innocuous drugs. The current study was aimed at investigating the antipyretic, anti-inflammatory and analgesic activity of methanol extract of A. hydaspica aerial parts (AHM) and its active fraction. Furthermore identification and isolation of polyphenolic compounds was carried out to identify the active principles.

Methods

Yeast induced pyrexia, Paw edema, acetic acid-induced writhing and hot plate test were carried out in vivo. HPLC-DAD analysis and combination of different chromatographic techniques, involving vacuum liquid chromatography (VLC) and flash chromatography (FC) were carried out for chemical characterization. The structural heterogeneity of flavanols was characterized by ESI- MS, ¹H NMR, ¹³C NMR and ²D NMR spectroscopic analyses, and also by comparison with reported literature.

Results

Oral administration of A. hydaspica methanol extract (AHM) and A. hydaspica ethyl acetate fraction (AHE), showed dose and time dependent decrease in body temperature in yeast induced pyrexia, comparable to standard, Paracetamol. AHM and AHE (150 mg/kg) significantly (p?<?0.001) inhibit pain sensation in various pain models, i.e. acetic acid induced writhing and hot plate test. Similarly AHM and AHE demonstrated an anti-inflammatory effect in carrageenan-induced paw edema in rats and 150 mg/kg dose being distinctly more effective (91.92% inhibition). When studied on prostaglandin E₂ (PGE₂) induced edema in rats, AHM and AHE showed maximum inhibition of edema at 150 mg/kg after 4 h. HPLC chromatogram of AHM revealed the presence of gallic acid, catechin, rutin and caffeic acid. Chromatographic separation and structure characterization of AHE, has led to the identification of three flavan-3-ol derivative including 7-O-galloyl catechin, +catechin and methyl gallate, which have been reported for the first time in A. hydaspica.

Conclusion

These results revealed that the presence of bioactive compounds in A. hydaspica might be responsible for the pharmacological activities, confirming the indigenous utility of A. hydaspica against inflammatory disorders.

     

Estimation of flavoniods,antimicrobial, antitumor and anticancer activity of <Emphasis Type="Italic">Carissa opaca</Emphasis> fruits

Background

Carissa opaca Stapf ex Hanes fruits is traditionally used in the treatment of asthma, hepatitis and microbial infections. The present study was arranged to investigate the antimicrobial, cytotoxic and antitumor activity of various fractions of C. opaca extract and its bioactive metabolites responsible for that activity.

Methods

To characterize various fractions of C.opaca antibacterial, antifungal, cytotoxic and antitumor assays are used. Eight strains of bacteria including Bacillus subtilis, Enterobactor aerogenes, Escherichia coli, Klebsiella pneumoniae, Micrococcus luteus, Pseudomonas aeroginosa, Salmonella typhy, and Staphylococcus aureus and four strains of fungal viz: Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger and Fusarium solani are used. Brine shrimps and potato dics are used for anticancer and antitumor potency of extract. High performance liquid chromatography (HPLC) is utilized for determination of bioactive metabolites responsible for the activity.

Results

HPLC chromatogram revealed the presence of orientin, isoquercetin, myricetin and apigenin. Various fractions of C. oapca showed significant antibacterial, antitumor and anticancer activity. In case of C. opaca fruit inhibition growth of Aspergillus niger was ranged between 23.2?±?1.36% to 43.3?±?2.39%, Aspergillus flavus ranged between 27.6?±?1.39% to 65.6?±?3.44%, Aspergillus fumigatus ranged between 13.2?±?1.00% to 52.4?±?1.54% and Fusarium solani ranged between 10.5?±?1.02% to 14.6?±?1.74%.

Conclusion

It can be concluded that, various fractions of C.opaca are accessible source of ethno pharmacy as they are consumed in different areas of Pakistan with ultimate health compensations.

     

Dendrimer-mediated delivery of <Emphasis Type="Italic">N</Emphasis>-acetyl cysteine to microglia in a mouse model of Rett syndrome

Background

Rett syndrome (RTT) is a pervasive developmental disorder that is progressive and has no effective cure. Immune dysregulation, oxidative stress, and excess glutamate in the brain mediated by glial dysfunction have been implicated in the pathogenesis and worsening of symptoms of RTT. In this study, we investigated a new nanotherapeutic approach to target glia for attenuation of brain inflammation/injury both in vitro and in vivo using a Mecp2-null mouse model of Rett syndrome.

Methods

To determine whether inflammation and immune dysregulation were potential targets for dendrimer-based therapeutics in RTT, we assessed the immune response of primary glial cells from Mecp2-null and wild-type (WT) mice to LPS. Using dendrimers that intrinsically target activated microglia and astrocytes, we studied N-acetyl cysteine (NAC) and dendrimer-conjugated N-acetyl cysteine (D-NAC) effects on inflammatory cytokines by PCR and multiplex assay in WT vs Mecp2-null glia. Since the cysteine-glutamate antiporter (Xc^?) is upregulated in Mecp2-null glia when compared to WT, the role of Xc^? in the uptake of NAC and l-cysteine into the cell was compared to that of D-NAC using BV2 cells in vitro. We then assessed the ability of D-NAC given systemically twice weekly to Mecp2-null mice to improve behavioral phenotype and lifespan.

Results

We demonstrated that the mixed glia derived from Mecp2-null mice have an exaggerated inflammatory and oxidative stress response to LPS stimulation when compared to WT glia. Expression of Xc^? was significantly upregulated in the Mecp2-null glia when compared to WT and was further increased in the presence of LPS stimulation. Unlike NAC, D-NAC bypasses the Xc^? for cell uptake, increasing intracellular GSH levels while preventing extracellular glutamate release and excitotoxicity. Systemically administered dendrimers were localized in microglia in Mecp2-null mice, but not in age-matched WT littermates. Treatment with D-NAC significantly improved behavioral outcomes in Mecp2-null mice, but not survival.

Conclusions

These results suggest that delivery of drugs using dendrimer nanodevices offers a potential strategy for targeting glia and modulating oxidative stress and immune responses in RTT.

     

The relationship between lymphovascular invasion and angiogenesis,hormone receptors,cell proliferation and survival in patients with primary operable invasive ductal breast cancer

Background

Several well-established tumour prognostic factors are used to guide the clinical management of patients with breast cancer. Lymphovascular invasion and angiogenesis have also been reported to have some promise as prognostic factors. The aim of the present study was to examine the prognostic value of tumour lymphovascular invasion and microvessel density compared with that of established prognostic factors in invasive ductal breast cancer.

Methods

In addition to hormone receptor status and Ki-67 proliferative activity, lymphovascular invasion and microvessel density and their relationship with survival were examined in patients with invasive ductal breast cancer. Full sections and tissue microarrays (n?=?384 patients) were utilised to assess these factors and were scored by appropriate methods.

Results

On univariate analysis tumour size (P?<?0.05), lymph node involvement (P?<?0.01), lymphovascular invasion (P?<?0.05), microvessel density (P?<?0.05) and local- regional treatment (P?<?0.01) were associated with poorer survival in ER negative tumours. On multivariate analysis in ER negative tumours lymph node involvement (P?<?0.01) and local- regional treatment (P?<?0.05) were independently associated with poorer cancer-specific survival. On univariate analysis tumour grade (P?<?0.05), lymph node involvement (P?<?0.001), HER-2 (P?<?0.05), Ki-67 (P?<?0.01) and lymphovascular invasion (P?<?0.001) were associated with poorer survival in ER positive tumours. On multivariate analysis lymph node involvement (P?<?0.001), Ki-67 (P?<?0.001) and lymphovascular invasion (P?<?0.05) were independently associated with poorer cancer-specific survival in ER positive tumours.

Conclusion

Lymphovascular invasion but not microvessel density was independently associated with poorer survival in patients with ER positive but not ER negative invasive ductal breast cancer.

     

Cardiac function evaluation for a novel one-step detoxification product of <Emphasis Type="Italic">Aconiti Lateralis Radix Praeparata</Emphasis>

Background

Aconiti Lateralis Radix Praeparata has been used as the first cardiac drug over a 1000 years in Asian countries. Although most detoxification products are confirmed to be safe, the effect is not potent as desired. In previous study, we designed a one-step detoxification product by fresh cutting and continuously dried, which preserved more water-soluble alkaloids while eliminating toxicity. It is thus necessary to find more in vivo evidence to support its industrial development.

Methods

Initially, network pharmacology was applied to analyze the related pathways of candidate components acting on heart failure diseases. Then, two heart failure models that were induced by propafenone hydrochloride and nimodipine (v/v, 1:1) and were given doxorubicin were carried out to test the cardiac activity. Moreover, the effect on mitochondrial energy metabolism was further assessed.

Results

Network pharmacology results indicated that Aconiti Lateralis Radix Praeparata treated heart failure through cAMP signaling pathway, calcium signaling pathway, adrenergic signaling in cardiomyocytes and so on. These pathways were highly correlated with myocardial contractility and mitochondrial energy metabolism. Trials on heart failure rats demonstrated that the novel processed-product could produce a stronger positive inotropic action and increase more Na⁺–K⁺–ATPase and Ca²⁺–Mg²⁺–ATPase than Heishunpian. Pathological results also revealed the novel one could better restore the morphology of cardiomyocytes and reduce vacuolar lesions. It also could inspire more energy with a lower concentration.

Conclusions

This study provides scientific evidence for the clinical application of new products. It is of great benefit to innovate the industrial detoxification process of Aconitum.

     

Hypoglycemic and hypolipidemic effects of <Emphasis Type="Italic">Bersama engleriana</Emphasis> leaves in nicotinamide/streptozotocin-induced type 2 diabetic rats

Background

The present investigation was aimed at evaluating the hypoglycemic and hypolipidemic properties of the aqueous and methanolic extracts from Bersama engleriana leaves in streptozotocin/nicotinamide (STZ-NA)-induced type 2 diabetic rats.

Methods

Animals were orally treated for 4 consecutive weeks with Bersama engleriana extracts at doses of 300 or 600 mg/kg. The anti-diabetic effect was examined by measuring blood glucose (BG) at 0, 1, 14 and 28 days after STZ-NA treatment and, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) levels at sacrifice (day 29). Glibenclamide (0.25 mg/kg) was used for comparison.

Results

STZ-NA-induced diabetic rats showed moderate to significant increases in the levels of BG, TG, TC, LDL-C while body weight, HDL-C levels and relative weights of liver and pancreas were decreased compared to controls (non diabetic rats). Administration of the plant extracts to STZ-NA diabetic rats resulted in a significant decrease in BG, TG, TC and LDL-C and the dose 600 mg/kg of the methanolic extract was the most effective; HDL-C level was markedly increased after four weeks compared to untreated diabetic rats. A dose-dependent increase in the relative weights of the diabetogenic organs was observed in the Bersama engleriana groups. It can be also noticed that the methanolic extract, especially the dose 600 mg/kg (p<0.001), produced more effects than glibenclamide and aqueous extract. Rats treated with glibenclamide (0.25 mg/kg) generally gave lower results compared to groups treated with plant extracts.

Conclusion

Results of the present study showed that Bersama engleriana extracts and especially its methanolic extract possess antidiabetogenic properties and beneficial effects on diabetic hyperlipidemia. All these effects could be due to the bioactive components revealed in the Bersama engleriana extracts such as triterpenes and phenols and which could justify its ethnomedical use.

     

Antinociceptive and anti-inflammatory activities of <Emphasis Type="Italic">Geranium bellum</Emphasis> and its isolated compounds

Background

Geranium bellum Rose, locally known as “Pata de león”, is a perennial plant distributed in the mountains of Hidalgo, Mexico. It is widely used in Mexican traditional medicine to treat fever, pain, and gastrointestinal disorders. To date, there are not published studies regarding the in vivo antinociceptive and anti-inflammatory potential of the acetone-aqueous extract from the aerial parts of G. bellum.

Methods

Antinociceptive effects of the acetone-aqueous G. bellum (AGB) extract and the isolated compounds were assessed using experimental pain models, including thermal nociception like hot plate test, and chemical nociception induced by intraperitoneal acetic acid or subplantar formalin injection in vivo. The anti-inflammatory properties of the extract were studied using systemic administration in carrageenan-induced paw edema.

Results

Intra-gastric administration of AGB (75, 150, and 300 mg/kg) showed a dose-dependent antinociceptive effect in intraperitoneal acetic acid (writhing), thermal nociception in CD1 mice, and subplantar formalin models, as well as anti-inflammatory effect in carrageenan- induced paw edema in Wistar rats. Geraniin and quercetin showed the highest antinociceptive activity in writhing test, whereas ellagic acid was the most active compound in the hot plate model.

Conclusion

These studies provide evidences that G. bellum shows antinociceptive and anti- inflammatory effects, and gives support to its use in treating pain in Mexican traditional medicine.

     

Identification of a novel loss-of-function mutation of the <Emphasis Type="Italic">GLA</Emphasis> gene in a Chinese Han family with Fabry disease

Background

Fabry disease is an X-linked recessive lysosomal disorder caused by deficient enzymatic activity of α-galactosidase A (α-Gal A). The insufficient enzymatic activity leads to excessive accumulation of glycosphingolipids, the substrates of the enzyme, in lysosomes in organs and tissues. Mutations in the α-Gal A gene (GLA, Xq22) have been proven to be responsible for Fabry disease.

Methods

In this study, we report a four-generation pedigree with left ventricular hypertrophy and chronic renal failure that was diagnosed by sequencing the GLA gene. An over expression system was constructed to evaluate the function of the detected mutation.

Results

We identified a novel mutation in exon 6 of the GLA gene, p.Asn278Lys, which completely co-segregated with the disease phenotype. The protein level of α-Gal A was significantly lower in the variant group than in the wild-type group; additionally, the pharmacological chaperone 1-deoxy-galactonojirimycin (DGJ) effectively normalized the enzyme activity of α-Gal A and its decline at the protein level.

Conclusions

This study is the first to report a novel loss-of-function mutation, p.Asn278Lys, in exon 6 of the GLA gene as a genetic aetiology for Fabry disease. In addition, we analysed the feasibility of DGJ as a therapeutic approach for this particular GLA mutation.

     

Cognitive-Behavioural Therapy for Inflammatory Bowel Disease: 24-Month Data from a Randomised Controlled Trial

Purpose

There is ongoing controversy on the effectiveness of psychotherapy in inflammatory bowel disease (IBD). In the few small studies, cognitive-behavioural therapy (CBT) has been shown to alleviate symptoms of anxiety or depression. However, there is little research on the impact of CBT on physical outcomes in IBD and no studies on long-term effectiveness of CBT.

Methods

The present two-arm pragmatic randomised controlled trial aimed to establish the impact of CBT on disease course after 24 months of observation. The study compared standard care plus CBT (+CBT) with standard care alone (SC). CBT was delivered over 10 weeks, face-to-face (F2F) or online (cCBT). The data were analysed using linear mixed-effects models.

Results

CBT did not significantly influence disease activity as measured by disease activity indices at 24 months (Crohn’s Disease Activity Index (CDAI), p?=?0.92; Simple Clinical Colitis Activity Index (SCCAI), p?=?0.88) or blood parameters (C-reactive protein (CRP), p?<?0.62; haemoglobin (Hb), p?=?0.77; platelet, p?=?0.64; white cell count (WCC), p?=?0.59) nor did CBT significantly affect mental health, coping or quality of life (all p?>?0.05).

Conclusions

Therefore, we conclude that CBT does not influence the course of IBD over 24 months. Given the high rate of attrition, particularly in the CBT group, future trials should consider a personalised approach to psychotherapy, perhaps combining online and one-to-one therapist time.

     

Does attendance at anatomy practical classes correlate with assessment outcome? A retrospective study of a large cohort of undergraduate anatomy students

Background

Anatomy in medical curricula is typically taught via pedagogy consisting of didactic lectures combined with a practical component. The practical component often includes traditional cadaveric dissection classes and/or workshops utilizing anatomical models, carefully prosected cadaveric material and radiology. The primary aim of this study was to determine if there is an association between attendance at practical classes in anatomy and student assessment outcomes. A secondary aim was to determine if student assessment outcomes were better when students preferentially attended workshops or prosection style practical classes.

Method

We retrospectively examined practical attendance records and assessment outcomes from a single large anatomy subject (approx. 450 students) to identify how attendance at anatomy practical classes correlates with assessment outcome.

Results

Students who scored above the median mark for each assessment attended significantly more practical classes than students who scored below the median assessment mark (Mann Whitney; p?<?0.001), and students who attended more than half the practical classes had significantly higher scores on assessments than students that attended less than half the practical classes (Mann Whitney; P?<?0.01). There was a statistically significant positive correlation between attendance at practical classes and outcomes for each assessment (Spearman’s correlation; p?<?0.01). There was no difference in assessment outcomes for students who preferentially attended more dissection compared to prosection style classes and vice versa (Mann Whitney; p?>?0.05).

Conclusions

Our findings show there is an association between student attendance at practical classes and performance on anatomy assessment.

     

Asthma and Hypogammaglobulinemia: an Asthma Phenotype with Low Type 2 Inflammation

Purpose

Little is known about hypogammaglobulinemia (HGG) in asthma patients. No data are available on the characteristics of adult patients with asthma and HGG.

Methods

We conducted a retrospective monocentric study between January 2006 and December 2012. Asthma patients with a serum immunoglobulin (Ig) quantitative analysis were included and classified into two groups depending on their serum IgG concentration: presence or absence of HGG. Clinical, biological, functional, and radiologic characteristics were compared in univariate and multivariate analysis, using a logistic regression model.

Results

In univariate analysis, asthma patients with HGG (n?=?25) were older (58 years old?±?18 vs 49?±?18, p?=?0.04) and more frequently active or former smokers as compared to patients with normoglobulinemia (n?=?80) (56.0 vs 35.0 %, p?=?0.01). Total IgE?<?30 kUI/L was more frequently observed in patients with HGG (53.0 vs 18.3 %, p?=?0.01). HGG asthma patients had lower fraction of exhaled nitric oxide (p?=?0.02), blood eosinophilia (p?=?0.0009), and presented with more severe composite score for bronchiectasis (p?=?0.01). In multivariate analysis, asthma patients with HGG had increased risk of being smokers [OR?=?6.11 (IC 95 %?=?1.16–32.04)], having total IgE concentration?<?30 kUI/L [OR?=?12.87 (IC 95 %?=?2.30–72.15)], and a more severe composite score of bronchiectasis [OR?=?20.65 (IC 95 %?=?2.13–199.74)].

Conclusion

Asthma patients with HGG are older and more often tobacco smoker than asthma patients without HGG. These patients have low type-2 inflammation markers.

     

Diagnostic efficacy of multiple MRI parameters in differentiating benign vs. malignant thyroid nodules

Background

Diffusion weighted imaging (DWI) has a good diagnostic value for malignant thyroid nodules, but the published protocols suffer from flaws and focus on the apparent diffusion coefficient (ADC). This study investigated the diagnostic performance of multiple MRI parameters in differentiating malignant from benign thyroid nodules.

Methods

This was a retrospective study of 181 consecutive patients (148 benign and 111 malignant nodules, confirmed by pathological results). The patients underwent conventional MRI, DWI, and dynamic contrast-enhanced MRI before surgery. The chi-square test and the Student t test were used to compare the conventional features and ADC value between malignant and benign groups. Multivariate logistic regression was used to identify the independent predictors and to construct a model. Receiver operator characteristic (ROC) curve analysis was used to assess the diagnostic performance of the independent variables and model.

Results

Tumor diameter, ADC value, cystic degeneration, pseudocapsule sign, high signal cystic area on T1-weighted imaging, ring sign in the delayed phase, and irregular shape showed significant differences between two groups (all P?<?0.05). The multivariable analysis revealed that ADC value (OR?=?694.006, P?<?0.001), irregular shape (OR?=?32.798, P?<?0.001), ring sign in the delayed phase (OR?=?20.381, P?=?0.004), and cystic degeneration (OR?=?8.468, P?=?0.016) were independent predictors. Among them, ADC performed the best in discriminating benign from malignant nodules, with an area under the curve (AUC) of 0.95, 0.90 sensitivity, and 0.91 specificity. When the independent factors were combined, the diagnostic performance was improved with an AUC of 0.99, 0.97 sensitivity, and 0.95 specificity.

Conclusions

ADC value could discriminate between benign and malignant thyroid nodules with a good performance. Subjective features such as the ring sign, irregular shape, and cystic degeneration associated with malignant thyroid nodules could provide complementary information for differentiation.

     

<Emphasis Type="Italic">ACTA2</Emphasis> mutation and postpartum hemorrhage: a case report

Background

ACTA2 encodes smooth muscle specific α-actin, a critical component or the contractile complex of vascular smooth muscle. Mutations in ACTA2 are the most common genetic cause of thoracic aortic aneurysm, and are also the cause of other disorders, including Moyamoya disease, coronary artery disease and stroke as well as Multisystemic Smooth Muscle Dysfunction Syndrome. We note that ACTA2 is also expressed in uterine smooth muscle, and this raises the possibility that women harboring ACTA2 mutations might exhibit uterine smooth muscle dysfunction.

Case presentation

We present a young woman whose ACTA2 mutation was ascertained during pregnancy because of her father’s history of dissecting aneurysms. She was delivered at full term by cesarean section and subsequently had severe uterine hemorrhage due to uterine atony. Although her atony was successfully treated with uterotonic medications, she required blood transfusion.

Conclusions

This case raises the possibility that women with ACTA2 mutations may be at risk of uterine muscle dysfunction and hemorrhage. Obstetricians should be alerted to and prepared for this possibility.

     

<Emphasis Type="Italic">SERPING1</Emphasis> mRNA overexpression in monocytes from HIV+ patients

Objective

The HIV-1 virus activates the complement system, an essential element of the immune system. SERPING1 is a protease inhibitor that disables C1r/C1s in the C1 complex of the classical complement pathway.

Methods

In this paper, we performed an analysis of several microarrays deposited in GEO dataset to demonstrate that SERPING1 mRNA is modulated in CD14⁺ monocytes from HIV-1-infected individuals. In addition, data were validated on monocytes isolated from seronegative healthy volunteers, treated with IFNs.

Results

Our analysis shows that SERPING1 mRNA is overexpressed in monocytes from HIV-1+ patients and the expression levels correlate positively with viral load and negatively with the CD4⁺ T-cell count. Of note, anti-retroviral therapy is able to reduce the levels of SERPING1 mRNA, ex vivo. In addition, we found that 30% of the SERPING1 genes network is upregulated in monocytes from HIV-1+ patients. Noteworthy, the expression levels of IFITM1—an antiviral molecule belonging to the genes network—correlate positively with SERPING1 expression. Interestingly, the monocytes treatment with IFN-gamma, IFN-beta and IFN-alpha significantly upregulates the SERPING1 mRNA expression levels.

Conclusions

From the outcome of our investigation, it is possible to conclude that SERPING1 and its network serve as important components of the innate immune system to restrict HIV-1 infection.

     

Association of hyperhomocysteinemia with genetic variants in key enzymes of homocysteine metabolism and methotrexate toxicity in rheumatoid arthritis patients

Objectives

The study investigated the association between plasma homocysteine, folate and vitamin B12 with 5,10 methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TYMS 2R → 3R) and methionine synthase (MTR A2756G) polymorphisms and methotrexate (MTX) treatment and toxicity in Tunisian Rheumatoid arthritis (RA) patients.

Methods

A total of 185 patients with RA were included. Homocysteine (Hcy) was assessed by fluorescence polarization immunoassay, and folate and vitamin B12 were measured by chemiluminescence immunoassays. The genetic polymorphisms were analyzed by PCR or PCR-RFLP. Hyperhomocysteinemia (HHC) was considered for Hcy?>?15 µmol/L.

Results

MTHFR C677T polymorphism was associated with HHC in RA patients (multi-adjusted OR, 95% CI 2.18, [1.07–4.57]; p?=?0.031). No association was detected with the remaining polymorphisms. Plasma Hcy, folate, and vitamin B12 did not differ according to each polymorphism, or with MTX treatment or toxicity. However, HHC was more prevalent in patients with than those without MTX toxicity (32.7 vs. 16.7%; p?=?0.035).

Conclusions

The MTHFR 677TT genotype is an independent risk factor for HHC in Tunisians RA patients. HHC could be a useful marker of MTX toxicity in RA patients.