Croton cajucara crude extract and isolated terpenes: activity on Trypanosoma cruzi

Croton cajucara is a plant found in the Amazon region and is known for its medicinal properties. The effects of the methanolic extract of the stem bark of C. cajucara (MCC) and of the isolated terpenes, trans-dehydrocrotonin (t-DCTN) and acetyl aleuritolic acid (AAA), were investigated using four isolates of Trypanosoma cruzi. In assays with trypomastigotes, the extract was more active than the isolated compounds, presenting IC₅₀ in the range of 10 to 50 μg/mL. The trypanocidal effect of MCC, AAA and benznidazole was significantly higher in the GLT291 and C45 strains, which were recently isolated from wild animals. MCC and AAA caused a dose-dependent inhibition of epimastigote proliferation. In assays using intracellular amastigotes, AAA and MCC reduced the percent of infection and the endocytic index after 96 h of treatment, at concentrations that were non-toxic to the host cells. MCC inhibited the trypanothione reductase pathway in both epimastigotes and trypomastigotes of all the subpopulations. The absence of AAA activity on the trypanothione reductase pathway in epimastigotes of Dm28c suggests heterogeneity of the biochemical profile between this clone and the three strains. Epimastigotes and trypomastigotes (GLT291) were treated for 24 h with MCC or AAA, and both induced alterations of the plasma membrane, while AAA-treated epimastigotes also displayed mitochondrial damage.     

Familial cryptic translocation (2;17) ascertained through recurrent spontaneous abortions

We report a young woman who presented with a reproductive history of three recurrent spontaneous abortions (RSA) and two neonatal deaths. Comparative genomic hybridization (CGH) was used to determine the chromosomal composition of the patient's last miscarriage. It showed the presence of monosomy for the distal end of chromosome 2 long arm (segment 2q37.2 to qter) and trisomy for the distal end of chromosome 17 long arm (segment 17q25 to qter). The mother was found to be a carrier for a cryptic translocation between chromosomes 2 and 17 long arms by fluorescence in situ hybridization using a subtelomeric probe for 17q. Retrospective CGH analysis on one baby who died neonatally showed that he had inherited the maternal translocation in the same unbalanced state as the last pregnancy loss. His detailed postmortem examination is reported.     

C-KIT expression in ductal carcinoma in situ of the breast: co-expression with HER-2/neu

The proto-oncogene c-KIT (CD117) is highly expressed in normal breast epithelium and is decreased in invasive breast cancer. In this study, we analyzed the protein expression and the mutational status of c-KIT in ductal carcinoma in situ (DCIS) of the breast and correlated these findings with nuclear grade, architectural pattern, and expression of HER-2, estrogen receptor (ER)-alpha, and progesterone receptor (PR). C-KIT, HER-2, ER, and PR expression were analyzed immunohistochemically in 106 cases of paraffin-embedded DCIS (85 pure DCIS and 21 DCIS with concurrent carcinoma). Direct sequencing of exons 9 and 11 of the c-KIT gene was performed to analyze the hot spot mutational regions in representative cases. C-KIT expression was found in 55 (52.8%) of all DCIS, correlating with high nuclear grade (P < .0001), comedonecrosis (P < .0001), and solid growth pattern (P = .001). Furthermore, c-KIT expression was strongly associated with HER-2 positivity (P < .0001) and was significantly lower in ER- or PR-positive cases (P = .001 and P = .006, respectively). C-KIT expression alone or co-expression with HER-2 in pure DCIS did not differ significantly from DCIS with invasive component (P = .09). Mutational analysis in 6 c-KIT-positive DCIS revealed no activating mutations in exons 9 or 11. Our findings suggest that the expression of c-KIT protein might define a subset of poorly differentiated, HER-2-positive DCIS with decreased expression of steroid hormone receptors, comedonecrosis, and a solid growth pattern. The implications of c-KIT and HER-2 co-expression for breast carcinogenesis should be further evaluated.     

Detection of new methicillin-resistant Staphylococcus aureus clones containing the toxic shock syndrome toxin 1 gene responsible for hospital- and community-acquired infections in France

Methicillin-resistant Staphylococcus aureus (MRSA) clones harboring the toxic shock syndrome toxin 1 (tst) gene have been detected in France and in Switzerland since 2002. During a passive survey conducted between 2002 and 2003, we collected 103 tst-positive S. aureus isolates from 42 towns in France, of which 27 were resistant to methicillin. The tst-positive MRSA belonged to two clones: a major clone comprising 25 isolates of sequence type (ST) 5 and agr group 2 and a minor clone comprising two isolates of ST30 and agr3. The tst-positive MRSA clones were associated with both hospital-acquired (12 cases) and community-acquired (8 cases) infections. The MRSA clones were mainly isolated from children (overall median age, 3 years). They caused a variety of clinical syndromes, including toxic shock syndrome and suppurative infections. Both clones were found to harbor a type IV staphylococcal chromosomal cassette mec (SCCmec) and to have similar antibiotic resistance profiles (usually resistant to oxacillin, kanamycin, and tobramycin and with intermediate resistance to fusidic acid). The origin of these clones is unclear. The tst-positive agr2 MRSA clone has the same sequence type (ST5) of two pandemic nosocomial MRSA clones, namely, the Pediatric clone and the New York/Japan clone. These findings suggest that all these clones are phylogenetically related. The pulsotype of the tst-positive MRSA clones differed from that of methicillin-sensitive S. aureus (MSSA) clones by a single band involving the SCCmec element. These findings suggest that the tst-positive MRSA clones may have emerged from their respective MSSA counterparts.     

Microfluidic devices for studies of primary cilium mediated cellular response to dynamic flow conditions

We present the first microfabricated microfluidic devices designed specifically for studies of primary cilium mediated cellular response to dynamic flow. The primary cilium functions as a mechano-sensor in renal tubular epithelium, sensing the extracellular fluid flow. Malfunction of cilia has been implicated in e.g. polycystic kidney disease and other pathological conditions. Bending of the primary cilium by fluid flow has been shown to give rise to an intracellular calcium signal, however little is known about the sensitivity to flow duration, magnitude and direction. This paper presents a novel method for studying cilia forming cells in asymmetric microfluidic environments. The microfluidic devices presented here were designed for a dynamic control of the local fluid flow on a cellular level, and thus, enables studies of cellular responses to an amplitude, frequency and direction controlled cilium movement.     

Reduced foreign body reaction to implanted biomaterials by surface treatment with oriented osteopontin

The foreign body reaction (FBR), which leads to the encapsulation of implanted biomaterials, has been implicated in the failure of many medical devices. The protein layer that is nonspecifically adsorbed onto the implant surface immediately after implantation is thought to dictate this reaction. It is hypothesized that biomaterial surfaces having specific proteins with precisely controlled orientations will decrease the FBR. Previously, we have reported that osteopontin (OPN) adsorbed on positively charged surfaces has a preferable orientation for in vitro cell adhesion and spreading as compared to negatively charged surfaces. It is expected that coating a layer of OPN in its preferred orientation on an implant surface will decrease the FBR. In this work, in vivo studies were performed to test this hypothesis. A positively charged polymer (p(HEMA-co-AEMA)) and a negatively charged polymer (p(HEMA-co-CEA)) coated with OPN were implanted subcutaneously in wild-type mice for 7 or 28 days. Uncoated polymers were used as control. For the 7-day implants, cells on OPN-coated p(HEMA-co-AEMA) spread more than cells on the other three materials. Following 28 days of implantation the implants were explanted and the capsule thickness and vascularity around the implants were characterized. Additionally, the macrophage and foreign body giant cells (FBGCs) around the implants were quantified. It was found in this study that the modification of the positively charged polymer surface with OPN in a controlled orientation led to a reduction in the foreign body reaction as determined by capsule thickness. Our finding provides valuable information for designing better biocompatible biomaterials with improved in vivo performance.     

Ethical challenges in connection with the use of coercion: a focus group study of health care personnel in mental health care

Background

In recent years, the attention on the use of coercion in mental health care has increased. The use of coercion is common and controversial, and involves many complex ethical challenges. The research question in this study was: What kind of ethical challenges related to the use of coercion do health care practitioners face in their daily clinical work?

Methods

We conducted seven focus group interviews in three mental health care institutions involving 65 multidisciplinary participants from different clinical fields. The interviews were recorded and transcribed verbatim. We analysed the material applying a ‘bricolage’ approach. Basic ethical principles for research ethics were followed. We received permission from the hospitals’ administrations and all health care professionals who participated in the focus group interviews.

Results

Health care practitioners describe ethical dilemmas they face concerning formal, informal and perceived coercion. They provide a complex picture. They have to handle various ethical challenges, not seldom concerning questions of life and death. In every situation, the dignity of the patient is at stake when coercion is considered as morally right, as well as when coercion is not the preferred intervention. The work of the mental health professional is a complicated “moral enterprise”.The ethical challenges deserve to be identified and handled in a systematic way. This is important for developing the quality of health care, and it is relevant to the current focus on reducing the use of coercion and increasing patient participation. Precise knowledge about ethical challenges is necessary for those who want to develop ethics support in mental health care. Better communication skills among health care professionals and improved therapeutic relationships seem to be vital.

Conclusions

A systematic focus on ethical challenges when dealing with coercion is an important step forward in order to improve health care in the mental health field.

     

Rosiglitazone Dampens Pulmonary Inflammation in a Porcine Model of Acute Lung Injury

The hallmarks of acute lung injury (ALI) are the compromised alveolar-capillary barrier and the extravasation of leukocytes into the alveolar space. Given the fact that the peroxisome proliferator-activated receptor-γ agonist rosiglitazone holds significant anti-inflammatory properties, we aimed to evaluate whether rosiglitazone could dampen these hallmarks of local pulmonary inflammation in a porcine model of lung injury. For this purpose, we used a model of lipopolysaccharide (LPS, 50 μg/kg)-induced ALI. One hundred twenty minutes following the infusion of LPS, we started the exposure to rosiglitazone through inhalation or infusion. We found that intravenous rosiglitazone significantly controlled local pulmonary inflammation as determined through the expression of cytokines within the alveolar compartment. Furthermore, we found a significant reduction of the protein concentration and neutrophil activity within the alveolar space. In summary, we therefore conclude that the treatment with rosiglitazone might dampen local pulmonary inflammation during the initial stages of ALI.     

Obstructive Sleep Apnea Syndrome Is Associated with Overactive Bladder and Urgency Incontinence in Men

Study Objective:

To investigate the incidence of overactive bladder (OAB) and urgency incontinence (UI) in men with obstructive sleep apnea syndrome (OSAS).

Design:

Prospective questionnaire study

Setting:

Saarland University Hospital

Patients:

All male patients who underwent full-night in-laboratory polysomnography between November 2006 and April 2007.

Interventions:

Overactive bladder symptom score (OABSS) and International Consultation on Incontinence Questionnaire, Short-Form (ICIQ-SF).

Measurements and Results:

OSAS severity was assessed according to the apnea-hypopnea-index (AHI). Return rate of questionnaires was 100% (n = 100). Patients with upper airway resistance syndrome (UARS) served as controls. Evaluation of OABSS revealed that patients with moderate and severe OSAS presented with a significantly higher incidence of symptoms of OAB than patients with mild OSAS and UARS (P < 0.05). Further, the ICIQ-SF revealed a higher occurrence of UI in patients with severe OSAS than in those with mild OSAS and UARS (P < 0.05).

Conclusions:

Increasing severity of OSAS appears to be associated with an increasing occurrence of overactive bladder and urgency incontinence in men. This relationship may have clinical implications for the treatment of affected patients.

Citation:

Kemmer H; Mathes AM; Dilk O; Gröschel A; Grass C; Stöckle M. Obstructive Sleep Apnea Syndrome Is Associated with Overactive Bladder and Urgency Incontinence in Men. SLEEP 2009;32(2):271-275.