Effects of black cohosh on the plasminogen activator system in vascular smooth muscle cells

Objective

The rhizome of the Cimicifuga racemosa plant (commonly known as black cohosh) has been used for menopausal complaints. Studies regarding the cardiovascular effects of black cohosh are lacking. We investigated the effect of black cohosh on the plasminogen activator system in cultured vascular smooth muscle cells (VSMCs).

Methods

VSMCs were isolated from rat aortae. Expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) proteins were evaluated by Western blot analysis and enzyme-linked immunosorbent assay, respectively. The activities of PAI-1 and t-PA in the conditioned media were assessed by fibrin overlay zymography. A 40% 2-propanol extract of black cohosh was used.

Results

Black cohosh extract (BcEx) stimulated the protein expression of PAI-1, but it did not affect that of t-PA. Vitamin E, a potent antioxidant, inhibited the BcEx-induced increase in PAI-1 expression, while ICI 182,780, an estrogen receptor antagonist, had no effect. Fibrin overlay zymography revealed that BcEx increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA by inducing a binding to PAI-1.

Conclusions

BcEx induces PAI-1 protein expression in the VSMCs likely via an oxidant mechanism. It also stimulates the enzyme activity of PAI-1 and reduces that of free t-PA. These findings suggest that black cohosh might exert a negative influence on fibrinolysis.     

Human hepatoma cells transmit surface bound HIV-1 to CD4 T cells through an ICAM-1/LFA-1-dependent mechanism

Background

During the viremic phase of human immunodeficiency virus type-1 (HIV-1) infection, hepatocytes are likely to be constantly exposed to circulating virions. Knowing that a contact between hepatocytes and CD4⁺ T lymphocytes is favoured by the local slow blood flow present within the liver, we hypothesize that hepatic cells can act as a viral reservoir and thus contribute to HIV-1 propagation.

Results

We report that human hepatoma cells bind and internalize HIV-1 particles. Infection of CD4⁺ T cells was found to be much more efficient following a contact with virus-loaded hepatocytes than with cell-free virus. Additional studies suggest that infection of CD4⁺ T cells in trans with hepatocytes carrying virus is primarily due to surface bound HIV-1 particles and relies on LFA-1/ICAM-1 interactions.

Conclusion

This work represents the first demonstration by which circulating CD4⁺ T cells can be potentially infected with HIV-1 through a contact with hepatocytes in the liver.     

MAPT gene rs1052553 variant is not associated with the risk for multiple sclerosis

Background/Objectives

Some experimental data suggest a possible role of tau protein in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis. The aim of this study was to investigate a possible influence of the SNP rs1052553 in the MAPT gene in the risk for relapsing bout onset (relapsing–remitting and secondary progressive) MS.

Methods

We analyzed the allelic and genotype frequency of MAPT rs1052553, which has been associated with some neurodegenerative diseases, in 259 patients with relapsing bout onset MS and 291 healthy controls, using TaqMan Assays.

Results

MAPT rs1052553 allelic and genotype frequencies did not differ significantly between relapsing bout onset MS patients and controls, and were unrelated with the age of onset of MS or gender.

Conclusions

These results suggest that MAPT rs1052553 polymorphism is not related with the risk for relapsing bout onset MS.     

Effects of Trifolium pratense and Cimicifuga racemosa on the endometrium of wistar rats

Objective

The aim of this study was to evaluate the effects of Trifolium pratense and Cimicifuga racemosa upon the endometrium of castrated female Wistar rats, comparing these results with a placebo and estradiol valerate.

Methods

Thirty-two adult castrated female Wistar rats were divided into four groups (eight rats per group) that receiving either tap water, estradiol valerate, isoflavones from T. pratense or deoxyactein from C. racemosa daily. The doses used were equivalent to normal doses used in humans. The results were analyzed by endometrial histology and the expression of α-estrogen receptor and protein Ki67. Both α-receptor and Ki67 expressions were determined by immunohistochemical and morphometric analysis.

Results

Endometrium histology stayed atrophic with both herbal extracts, but T. pratense supplementation increased the expression of α-estrogen receptors when compared to the placebo group, without protein Ki67 expression enhancement. Both herbal extracts presented a lower Ki67 expression when compared to the placebo group.

Conclusion

T. pratense presented α-estrogen receptor stimulation in the endometrium without increasing cell proliferation. Both herbal extracts reduced endometrial proliferation in comparison to the placebo group.     

Polymorphisms of genes related to endothelial cells are associated with primary biliary cirrhosis patients of Cretan origin

Background

Primary biliary cirrhosis (PBC) is an organ specific autoimmune disease of still unidentified genetic etiology. We have shown that endothelins (ETs), produced by the liver endothelial cells are increased in PBC and may play a major pathogenetic role.

Aims

To study gene polymorphisms related to the endothelial cells (eNOS, EDN-1 genes) and, to investigate whether the previously reported association of CTLA4 gene polymorphisms is replicated in a genetically homogeneous Greek population.

Patients and methods

Genomic DNA was extracted from 100 PBC patients (83 females, 93% AMA+, 74/100 Ludwig stage I–II) and 158 healthy controls. eNOS, CTLA4 and ET1 polymorphisms were determined by PCR–RFLPs analysis.

Results

Both eNOS intron4 VNTR and eNOS exon7 G894T SNP were significantly associated with increased risk in PBC. EDN-11 rs2071942 “A” and rs5370 “T” alleles appeared a tendency for association with disease progression. No association was found between PBC and the CTLA4 SNPs analyzed.

Conclusions

We demonstrated that eNOS, a gene related to the liver endothelium function is associated with PBC. Contrarily, the important in adaptive immunity gene CTLA4 was not associated with the disease in the homogeneous population analyzed. These results are compatible partially with our previous hypothesis that defects of the liver endothelial system, leading to endothelin overproduction, may be a fundamental early pathogenetic mechanism in PBC.     

"Piecemeal" necrosis: renamed troxis necrosis

Piecemeal necrosis, currently called interface hepatitis, is a feature of viral hepatitis as well as autoimmune hepatitis and steatohepatitis. The mechanism of liver cell loss and piecemeal necrosis needs to be determined. We hypothesize that piecemeal necrosis in hepatitis is due to a piecemeal removal of hepatocyte cytoplasm by lymphocytic ingestion. To test this hypothesis, 61 consecutive liver biopsies were examined by light microscopy, by immunohistochemistry and by electron microscopy, and the lymphocytic-hepatocytic interaction was morphologically assessed. In cases of hepatitis C, hepatitis B, autoimmune hepatitis, primary biliary cirrhosis, and steatohepatitis, piecemeal necrosis was found. Using cytokeratin stains, it was apparent that the lymphocyte-hepatocyte interaction and piecemeal necrosis leads first to binding of the lymphocyte to hepatocyte plasma membrane and then blebbing or indentation of the hepatocyte by the lymphocyte, followed by endocytosis of liver cell cellular components and digestion in the lymphocyte lysosomes. This process is repeated while the cytoplasm and the nucleus of the hepatocyte disappear bite by bite, and only nubbins of residual hepatocytic cytoplasm remain, either attached to intact hepatocytes or surrounded and sequestered within scar tissue and lymphocytes. We conclude that piecemeal necrosis is a gradual disappearance of hepatocytes as a result of lymphocyte-hepatocyte binding and ligand internalization of liver surface molecules by the lymphocyte. This gradual process leads to a slow reduction of hepatocyte size and eventual disappearance at the interface between the lobule and portal tracts. To term this new kind of necrosis, we propose the name troxis necrosis, after the Greek noun meaning "nibbling."     

Safety of herbal medicinal products in women with breast cancer

Objective

To review and summarise current evidence on the efficacy and safety of herbal medicinal products for the relief of hot flushes in women with previous breast cancer.

Methods

A literature search was conducted in the databases of Medline, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL), PSYCHINFO, AMED (Allied and Complementary Medicine), NCCAM (The National Centre for Complementary and Alternative Medicine).

Results

Black cohosh and phytoestrogens have received the most research attention but there is currently insufficient evidence to recommend either for relief of flushes. Black cohosh use appears safe in women with previous breast cancer. Opposing advice has been given regarding the safety of dietary phytoestrogen use for women with previous breast cancer, but there is emerging data that soyfood phytoestrogen intake may have a beneficial effect on tumour recurrence.

Conclusions

The majority of studies, regarding the efficacy of herbal treatments for hot flushes, have not been conducted in women with breast cancer and many are of short duration. Increased pharmacovigilance practices for herbal medicines are required with initiatives to stimulate reporting of suspected adverse reactions.     

Investigating the role of BDNF and CCK system genes in suicidality in a familial bipolar cohort

Background

Suicidal behaviour is a phenotype widely associated with psychiatric disorders such as major depressive disorder and bipolar disorder. However, recent evidence indicates that part of the heritability of suicidal behaviour is independent of the heritability of individual psychiatric disorders. This allows investigation into genetic risk factors for suicidal behaviour within a disorder using a candidate gene association approach.

Methods

We used family-based association testing in a cohort of 130 multiplex bipolar pedigrees, comprising 795 individuals, to look for associations between suicidal behaviour and 32 single nucleotide polymorphisms (SNPs) from across the genes brain-derived neurotrophic factor (BDNF), cholecystokinin (CCK) and the cholecystokinin beta-receptor (CCKBR).

Results

We found associations (p≤0.05) between suicide attempt and 12 SNPs of CCKBR and five SNPs of BDNF. After correction for multiple testing, seven SNPs of CCKBR remained significantly associated. No association was found between CCK and suicidal behaviour.

Limitations

The study relied on retrospective self-reporting by individuals to determine phenotype, and the sample size was relatively small.

Conclusions

The results of the study support the hypothesis that some CCKBR polymorphisms may contribute to an underlying predisposition towards suicidal behaviour in bipolar disorder.     

Méningo-encéphalite à Bartonella quintana chez un sujet immunocompétent : une observation rare

Introduction

Bartonella quintana (Bq) is responsible of various clinical pictures. Neuromeningeal complications are rarely reported.

Case

A 20-year-old woman was admitted for fever, headache lasting for 5 days. On admission, she was febrile at 39.3 °C and had a stiff neck. Symptoms, contact with animals, biological tests and lumbar puncture (PL) rendered viral meningitis a likely diagnosis. She had received symptomatic treatment and the outcome was favorable. Three days later, the patient had headache, agitation and confusion with fever. The PL noted 130/mm³ whites, 90% lymphocytes. The albuminorachie was 0.98 g/L, glucorachie was normal. The patient was treated with 400 mg of ofloxacine/day, seven days. Serologic tests for B. quintana were reactive. The outcome was favorable.

Conclusion

B. quintana infection should be considered in neurological symptoms of unknown etiology.     

Suspected black cohosh hepatotoxicity—Challenges and pitfalls of causality assessment

Objectives

Black cohosh (BC) is a herbal drug or herbal dietary supplement used for treatment of menopausal symptoms. Recently, however, reports have appeared about the occurrence of rare toxic liver disease in an assumed relationship with the use of BC.

Methods

We have analyzed and reviewed the data of all 69 reported cases with suspected BC hepatotoxicity. Causality for BC was assessed utilizing the scale of the original structured quantitative Council for International Organizations of Medical Sciences (CIOMS), or the main-test as its updated form.

Results

With the hepatotoxicity specific causality assessment methods, there was an excluded, unlikely, unrelated or unassessable causality for BC in 68 of 69 cases with liver disease. One patient had a possible causality for BC and a symptomatic cholelithiasis with confounding variables of fatty liver of unknown etiology; unknown BC brand including possible herbal mixture; unknown daily BC dosage; and an unassessable duration of BC usage. In general, the cases of the 69 patients were poorly documented. Confounding variables were: failure to identify the BC product; use of herbal mixtures with multiple ingredients in addition to BC; co-medication with synthetic drugs and dietary supplements including herbal ones; missing temporal association between BC use and development of liver disease; not specified modalities of BC treatment; failure of dechallenge after BC discontinuation; pre-existing liver diseases; insufficiently excluded other liver diseases; presence of alternative liver diseases.

Conclusions

The analysis of 69 cases shows little, if any, supportive evidence for a significant hepatotoxic risk of BC.     

No evidence of the APC D1822V missense variant's pathogenicity in Tunisian patients with sporadic colorectal cancer

Objectives

Sporadic colorectal cancer is influenced by numerous single nucleotide polymorphisms (SNPs), each with minor effects on the cancer risk. This study seeks to determine whether there is any association of the I1307K, E1317Q and D1822V variants within the Adenomatous polyposis coli gene (APC) and risk to develop colorectal cancer in Tunisian population.

Methods

Direct sequencing was used to investigate three SNPs in the APC in 48 Tunisian sporadic colorectal cancer cases and 63 controls.

Results

There was no statistically significant association between the I1307K, E1317Q and D1822V variants investigated and colorectal cancer risk.

Conclusion

The lack of association may show that these variants selected for this study are not involved in the colorectal carcinogenic process. Otherwise, the eventual biological effect is so little to go undetected, unless increasing the sample size.     

A comparative study on the reliability of an automated system for the evaluation of cell-based indirect immunofluorescence

Background

Automated interpretations systems for anti-nuclear antibody (ANA), anti-double stranded DNA antibody (dsDNAab), and anti-neutrophil cytoplasmic antibody (ANCA) assessment by indirect immunofluorescence (IIF) have been recently introduced. The aim of this study was to compare the diagnostic performance of the automated IIF reading system AKLIDES with both traditional visual interpretation of IIF by laboratory experts and confirmatory tests.

Methods

Visual and automated autoantibody interpretations of IIF findings using AKLIDES pattern recognition algorithms were performed for ANA on HEp-2 cells (n = 182), dsDNAab on Crithidia luciliae (n = 44) and ANCA on human neutrophils (n = 46). All serum samples tested by IIF for ANCA and dsDNAab were also assessed with the corresponding enzyme-linked immunosorbent assays (ELISAs). Out of the 182 sera tested for ANA by IIF, 116 were also assessed for antibodies to extractable nuclear antigens (ENA) by ELISA and dot immunoassay (DIA).

Results

ANA testing showed an excellent agreement between visual and AKLIDES reading (98.9%). The overall agreement of dsDNAab testing on C. luciliae substrate slides was 91.0%, whereas ANCA showed a concordance of 89.1%. There was a remarkable agreement of AKLIDES findings for dsDNAab with confirmatory tests.

Conclusion

Visual and automated interpretations of IIF findings for ANA, ANCA, and dsDNAab demonstrated a good agreement when assessing patients with suspected autoimmune diseases. Automated interpretation systems such AKLIDES may improve laboratory efficiency and support standardization of IIF in clinical laboratories.     

Effectiveness of a patient education intervention in enhancing the self-efficacy of hospitalized patients to recognize and report acute deteriorating conditions

Objective

To develop and pilot test the effectiveness of a patient education intervention in enhancing the self-efficacy of hospitalized patients to recognize and report symptoms of acute deteriorating conditions.

Method

Using cluster randomization, acute care general wards were randomized to the experimental and control groups. 34 patients in the experimental group received a 30-minute patient education intervention on Alert Worsening conditions And Report Early (AWARE) while 33 patients in the control group received the routine care only. Levels of self-efficacy to recognize and report symptoms were measured before and after the intervention.

Results

The level of self-efficacy reported by the experimental group was significantly higher than the control group (p < 0.0001).

Conclusion

The AWARE intervention was effective in enhancing the self-efficacy of hospitalized patients to recognize and report acute deteriorating conditions.

Practical implications

Patient engagement through patient education could be included in the rapid response system which aims to reduce hospital mortality and cardiac arrest rates in the general wards.     

JK1 (FAM134B) represses cell migration in colon cancer: a functional study of a novel gene

Background

JK1 is a novel cancer-related gene with unknown functional role in carcinogenesis. The aim of this study is to investigate the role of JK1 gene in carcinogenesis in an in vitro cell proliferation and migration analysis model.

Methods

Small hairpin RNAs (shRNA) were designed to knock-down JK1 expression in colon cancer cell line (SW480) using transduction ready lentiviral particles. Cell proliferation and cell migration assays were performed on multiple extracellular matrices to investigate the cellular effects of JK1 in colon cancer cells. A non-cancer colonic epithelial cell line (FHC) was used to compare the expression of JK1 in cancer cell line.

Results

JK1 knock-down did not affect cellular proliferation or survival in colon cancer. However, the manipulation increased cancer cell migration rates on collagen and fibronectin substrates.

Conclusions

JK1 was shown for the first time to have a functional role in the pathogenesis of colon cancer. The results imply that JK1 represses the capacity of cancer cells to migrate within their tissue. They also concurred with the previous findings of JK1 activity correlations with clinical and pathological features in colon cancer. The capacity may have utility as a means to prevent cancer cells forming metastases.     

Évaluation des activités antioxydante et anti-inflammatoire de Erica arborea L. du Maroc

Aim

The present study was carried out to evaluate the antioxidant and anti-inflammatory capacity, and acute toxicity of Moroccan Erica arborea leaves.

Methods

Antioxidant capacity was assessed by diphenyle-picryl-hydrazyl (DPPH), phosphomolybdate (PPM) and ferric reducing antioxidant power (FRAP) tests and anti-inflammatory capacity was evaluated by hind paw oedema model using carrageenan-induced inflammation in rat. The acute toxicity was evaluated using mice.

Results

Acute toxicity of ethanolic extract of E. arborea showed no sign of toxicity at dose of 5 g/kg B.W. Our extracts have important antioxidant properties. The efficient concentration of the ethanolic extract (10.22 μg/ml) required for decreasing initial DPPH concentration by 50% was comparable to that of standard solution butyl-hydroxy-toluene (BHT) (8.87 μg/ml). The administration of ethanolic extract at doses of 200 and 400 mg/kg B.W. was able to prevent plantar oedema and exhibited a significant inhibition against carrageenan-induced inflammation when compared to the control group (NaCl 0.9%) but comparable to those of diclofenac (reference drug).

Conclusions

Our results show that the leaves of E. arborea may contain some bioactive compounds which are responsible for the antioxidant and anti-inflammatory activities observed here. Our finding may indicate the possibility of using the extracts of this plant to prevent the antioxidant and inflammatory processes.     

Polymorphisms of the endothelial nitric oxide synthase gene in premenopausal women with polycystic ovary syndrome

Objectives

To investigate the association of two common genetic polymorphisms of the gene encoding for endothelial nitric oxide synthase (Nos3), the enzyme catalyzing the production of nitric oxide (NO), with occurrence of the polycystic ovary syndrome (PCOS).

Methods

In a prospective case–control study, we analyzed 2 polymorphisms of the Nos3 gene cluster (Nos 3 exon 7 Glu298Asp and 27-base pair repeat in intron 4 of Nos3) in a series of 210 premenopausal Caucasian women with PCOS and 171 healthy controls using pyrosequencing and PCR, respectively. Women completed a detailed questionnaire and underwent a peripheral venous puncture, ultrasonography, and a standardized oral glucose tolerance test (OGTT).

Results

Genotype frequencies were not significantly different among women with PCOS and controls for the exon 7Nos3 and the intron 4Nos3 polymorphism (p = 0.3 and 0.2, respectively).

Conclusions

In our series, two common polymorphisms of the Nos3 gene cluster were not associated with occurrence of PCOS.     

Genetic variants of the BDNF and DRD3 genes in bipolar disorder comorbid with anxiety disorder

Background

The high comorbidity rate between bipolar disorder (BP) and anxiety disorder (AD) has been studied in depth. This comorbidity is not as high in Han Chinese in Taiwan. Therefore, we explored the genetic effects BP comorbid with AD.

Methods

We recruited 1316 participants: 286 with BP-I, 681 with BP-II, and 349 healthy Controls. Genotypes of the BDNF Val66Met and DRD3 Ser9Gly polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis.

Results

The DRD3 Ser9Gly polymorphism was associated with BP-II comorbid with AD (BPII^+AD), and the BDNF Val66Met polymorphism was associated with BP-I comorbid with AD (BPI^+AD). An interaction between the Val/Val genotype of the BDNF Val66Met and Gly/Gly polymorphism of the DRD3 Ser9Gly was found in BPII^+AD, but not in BP-II not comorbid with AD (BPI^−AD) compared with healthy Controls.

Limitation

The low comorbidity rate of AD in both BP subtypes, especially BP-I, limit generalizing our findings.

Conclusion

The involvement of the dopaminergic pathway in AD was confirmed, particularly with BP-II rather than BP-I. Because the Val/Val genotype of the BDNF Val66Met polymorphism, rather than the other two polymorphisms, has been associated with anxiety, it seems to affect BP-I comorbid with AD without the involvement of the DRD3 Seg9Gly polymorphism, but may modify the involvement of DRD3 Gly/Gly in BP-II comorbid with AD.     

Applying qualitative methods in developing a culturally tailored workbook for black patients with hypertension

Objective

To apply qualitative research methods in developing a culturally tailored, educational workbook for hypertensive black patients.

Methods

The workbook was developed using formative qualitative data from 60 black primary care patients with hypertension. Participants were interviewed using qualitative methods and data were analyzed through sequential steps of open coding, axial coding, and selective coding. From these analyses, themes describing patients’ cultural beliefs about hypertension were derived and used to develop the workbook.

Results

The workbook, “Living With Hypertension: Taking Control” is a 37-page illustrated workbook with 11 chapters based on patients’ perceptions of hypertension. These chapters focus on strengthening participants’ ability to take control and manage hypertension and on providing knowledge and health behavior techniques.

Conclusion

Qualitative research methods were used to inform the development of a culturally tailored educational workbook.

Practice implications

The workbook developed in this study may offer a practical and effective means of educating patients about blood pressure control in primary care settings.     

Menopause and aging: Changes in the immune system—A review

Background

The higher risk of women developing autoimmune diseases suggests that immune system is mediated by sex steroids.

Objective

To review the effects of aging and menopause in immune system.

Methods

A systematic review of in vitro, animal and human studies involving aging and menopause and immune system was carried out. An electronic search based on Internet search engines, MEDLINE (1966–June 2010) and the Cochrane Controlled Clinical Trials Register was done.

Results

After crossing-cleaning the reference lists, a total of 688 studies dealing with immune system and menopause were identified. Of them, 30 were considered selectable. The concept of immunosenescence reflects changes in both cellular and serological immune responses throughout the process of generating specific response to foreign antigens. This may be related with a higher incidence of infectious and chronic diseases. After menopause, there is an increase in pro-inflammatory serum markers (IL1, IL6, TNF-alpha), an increase in response of the immune blood cells to these cytokines, a decrease in CD4 T and B lymphocytes and a decrease in the cytotoxic activity of NK cells. Additionally, IL-6 is a key factor in bone resorption and also seems to be associated with other diseases more common after menopause such as diabetes, atherosclerosis and cardiovascular disease.

Conclusions

Most of the studies suggested that in addition to age, in postmenopausal women, changes of the immune system have been attributed to estrogen deprivation. Furthermore, recent studies point out changes in immune response related to use or cessation of hormone replacement at menopause.     

Panic disorder and serotonergic genes (SLC6A4, HTR1A and HTR2A): Association and interaction with childhood trauma and parenting

Objective

The aim of this study is to evaluate the association between HTR1A, HTR2A and the 5-HTTLPR in panic disorder (PD) patients and controls. In addition, this study also aims to evaluate the interaction between these genes and two environmental factors previously associated with PD: childhood trauma and parental bonding.

Methods

This is a case–control candidate gene association study (107 PD patients and 125 controls). Genes were analyzed using a gene-based test in PLINK followed by single marker association tests and haplotype test only for genes that reached experiment-wide significance in the gene-based test in order to minimize multiple testing. Logistic regression was used to test the relationships between genotype in the additive model, trauma, optimal paternal parenting and optimal maternal parenting and their interactions.

Results

Only HTR1A was associated with PD in gene-based test after correction for multiple tests (p_corrected = 0.027) and one HTR1A haplotype comprising four SNPs was associated with PD (p_corrected = 0.032). In the interaction analysis, no significant gene–environment interaction was found with the genes evaluated.

Conclusion

This study reinforces the association between HTR1A and PD. No major evidence of gene–environment interaction in PD with parenting or trauma was found. Further studies are necessary in order to confirm these findings.