Role of synovial lymphatic function in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) affects the entire joint, initially with a low degree of inflammation. Synovitis is correlated with the severity of OA clinical symptoms and cartilage degradation. The synovial lymphatic system (SLS) plays a prominent role in clearing macromolecules within the joint, including the pro-inflammatory cytokines in arthritic status. Scattered evidence shows that impaired SLS drainage function leads to the accumulation of inflammatory factors in the joint and aggravates the progression of OA, and the role of SLS function in OA is less studied. DESIGN: This review summarizes the current understanding of synovial lymphatic function in OA progression and potential regulatory pathways and aims to provide a framework of knowledge for the development of OA treatments targeting lymphatic structure and functions. RESULTS: SLS locates in the subintima layer of the synovium and consists of lymphatic capillaries and lymphatic collecting vessels. Vascular endothelial growth factor C (VEGF-C) is the most critical regulating factor of lymphatic endothelial cells (LECs) and SLS. Nitric oxide production-induced impairment of lymphatic muscle cells (LMCs) and contractile function may attribute to drainage dysfunction. Preclinical evidence suggests that promoting lymphatic drainage may help restore intra-articular homeostasis to attenuate the progression of OA. CONCLUSION: SLS is actively involved in the homeostatic maintenance of the joint. Understanding the drainage function of the SLS at different stages of OA development is essential for further design of therapies targeting the function of these vessels.

Tiger nut (Cyperus esculentus) as a potential phytoinsecticide: larvicidal activity of crude extracts on Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae).

Plants contain bioactive compounds and are constantly explored as safer alternatives to conventional insecticides. Despite numerous studies on many plants, information on the insecticidal potential of underutilised plants like tiger nut, Cyperus esculentus L., are scant, although their pharmacological potentials are well known. Hence, this study investigated the larvicidal potential of crude aqueous extracts of two C. esculentus varieties (black and yellow) on the mosquitoes Aedes aegypti (L.) and Culex quinquefasciatus (Say). Mosquito larvae were exposed to C. esculentus crude extracts using the larval bioassay technique of the World Health Organization. Differential larvicidal responses were observed in the test mosquitoes and extracts of Black Dried Tiger nuts (BDT) were more larvicidal than Yellow Dried Tiger nuts (YDT). Acute larval toxicity of the extracts was more pronounced on Cx. quinquefasciatus than Ae. aegypti. The results indicate the potential of C. esculentus (particularly BDT) as a source of mosquito bioinsecticide and merits further studies as a safer alternative to conventional insecticide-based vector control.

Tiger nut (Cyperus esculentus) as a potential phytoinsecticide: larvicidal activity of crude extracts on Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae)

@#Plants contain bioactive compounds and are constantly explored as safer alternatives to conventional insecticides. Despite numerous studies on many plants, information on the insecticidal potential of underutilised plants like tiger nut, Cyperus esculentus L., are scant, although their pharmacological potentials are well known. Hence, this study investigated the larvicidal potential of crude aqueous extracts of two C. esculentus varieties (black and yellow) on the mosquitoes Aedes aegypti (L.) and Culex quinquefasciatus (Say). Mosquito larvae were exposed to C. esculentus crude extracts using the larval bioassay technique of the World Health Organization. Differential larvicidal responses were observed in the test mosquitoes and extracts of Black Dried Tiger nuts (BDT) were more larvicidal than Yellow Dried Tiger nuts (YDT). Acute larval toxicity of the extracts was more pronounced on Cx. quinquefasciatus than Ae. aegypti. The results indicate the potential of C. esculentus (particularly BDT) as a source of mosquito bioinsecticide and merits further studies as a safer alternative to conventional insecticide-based vector control.

Latex C-serum from Hevea brasiliensis induces non-apoptotic cell death in hepatocellular carcinoma cell line (HepG2).

OBJECTIVES: Latex from Hevea brasiliensis (natural rubber tree primarily cultivated for its rubber particles) has no known primary metabolic function, although its biological role is as a plant defence system. The present study has evaluated specific anti-proliferative effects of latex whole C-serum and its subfractions, on human cancer cell lines. MATERIALS AND METHODS: Cell viability assay using MTT, DNA fragmentation assay and real-time PCR were used to evaluate the cytotoxic effects of latex whole C-serum and its subfractions on the cell lines. RESULTS: MTT assay revealed very low LC(50) values, 2.0 and 280 ng/ml, for DCS and DCP treatments, respectively. DCS was proven to be more potent compared to DCP, in conferring specific anti-proliferative effects on the cancer cell lines. The study also indicated that anti-proliferative activity of pre-heated C-serum fractions diminished significantly. CONCLUSION: Although noteworthy cell death was reported, DNA fragmentation assay and real-time PCR confirmed that that induced by latex C-serum subfractions was not promoted via the classical apoptotic signalling pathway.

Anti-Candida albicans activity and brine shrimp lethality test of Hevea brasiliensis latex B-serum.

BACKGROUND AND OBJECTIVES: Hevea brasiliensis extracts could potentially be employed as a relatively low cost resource for various anti-fungal activities due to the simplicity of the extract preparation and its abundance especially in the tropical region. Latex B-serum was reported to have anti-cancer property and its specificity in anti-fungal property has not been elucidated. The present study was conducted to determine the anti-fungal activity of Hevea latex B-serum against Candida (C.) albicans (a rounded cell fungus) and Aspergillus (A.) niger (a filamentous fungus). METHODS AND RESULTS: The results showed that the anti-fungal activity of latex B-serum was specific to C. albicans but not to A. niger. The MIC value of latex B-serum for C. albicans was found to be 2.5 mg/ml. The time-killing profile showed that the growth of C. albicans was inhibited and the inhibition was prolonged throughout the tested time period. Brine shrimp toxicity test showed an LC50 of 461.0 mg/ml with latex B-serum, indicating the non-toxicity of the serum. CONCLUSION: Further purification and identification of the crude extract should point the way to bioactive compound(s) responsible for anti-Candida activity.

Anti-fungal effect of Hevea brasiliensis latex C-serum on Aspergillus niger.

OBJECTIVES: Hevea brasiliensis extract could potentially be employed as a relatively low cost resource for various anti-fungal activities due to the simplicity of latex preparation and the abundance of latex that can be obtained in rubber producing regions. The present study was aimed at examining the species specific anti-fungal property of H. brasilensis latex C-serum against Aspergillus niger. RESULTS: The results showed that the latex C-serum exerted a specific antifungal activity against Aspergillus niger, but not Candida albicans. Low toxicity of the C-serum was demonstrated in Brine Shrimp Lethality Test (BSLT) with an LC50 value of 98.4 mg/ml. CONCLUSIONS: Pending further more elaborated investigations, H. brasiliensis latex C-serum, with its species specific anti-fungal and cancer-origin cell line specific anti-proliferation properties, would probably contribute in healthcare in addition to its traditional role in polymer industry.

The trigeminocardiac reflex in Onyx embolisation of intracranial dural arteriovenous fistula.

We investigated the incidence of the trigeminocardiac reflex (TCR) during ethylene vinyl alcohol copolymer (Onyx Liquid Embolic System, ev3 Neurovascular, Irvine, CA, USA) embolisation of intracranial dural arteriovenous fistulas (DAVFs) and evaluated the post-procedural recovery of these patients. Between June 2006 and July 2009, 21 patients (11 females, 10 males) with a mean age of 61years (range: 25-85years) underwent 28 Onyx embolisations of intracranial DAVFs at our institution. The case histories of these patients were reviewed retrospectively. A TCR occurred in three (10.7%) of the embolisations, with bradycardia lower than 60 beats/minute and a drop in mean arterial blood pressure of 20% or more. The reflex was blunted promptly with intravenous atropine, and follow-up of these patients showed no complications that might have been directly related to it. The TCR may occur during Onyx embolisation of intracranial DAVFs. Recognition of this phenomenon allows for early detection and appropriate intraoperative management.

Murine embryonic fibroblasts lacking TC-PTP display delayed G1 phase through defective NF-kappaB activation.

Previous results suggested a potential role for T-cell protein tyrosine phosphatase (TC-PTP) in cell proliferation. However, no conclusive data has supported such a function in the modulation of this process. In order to clarify this issue, we isolated TC-PTP-/- murine embryonic fibroblasts (MEFs) as well as cell lines to characterize the role of TC-PTP in the control of cell proliferation and cell cycle. Both TC-PTP-/- primary MEFs and cell lines proliferate slower than TC-PTP+/+ cells. We also demonstrated that TC-PTP-/- cells have a slow progression through the G1 phase of the cell cycle. Further characterization of the G1 defect indicates that the kinetics of cyclin D1 induction was delayed and that p27(KIP1) remains at higher levels for an extended period of time. Moreover, cells lacking TC-PTP showed a delayed activation of CDK2. This slow progression through the early G1-phase resulted in decreased phosphorylation of the RB protein and subsequent delay into the S phase transition. In contrast, no further defects were detected in other phases of the cell cycle. Survey of the potential signaling pathways leading to this delayed cyclin D1 expression indicated that NF-kappaB activation was compromised and that IKKbeta activity was also reduced following PDGF stimulation. Reintroduction of wild-type TC-PTP into the TC-PTP-/- cells rescued the defective proliferation, cyclin D1 expression, NF-kappaB activation as well as IkappaB phosphorylation. Together, these results confirm that TC-PTP plays a positive role in the progression of early G1 phase of the cell cycle through the NF-kappaB pathway.

Specification of neurotransmitter receptor identity in developing retina: the chick ATH5 promoter integrates the positive and negative effects of several bHLH proteins.

Genetic studies in Drosophila and in vertebrates have implicated basic helix-loop-helix (bHLH) transcription factors in neural determination and differentiation. In this report, we analyze the role that several bHLH proteins play in the transcriptional control of differentiation in chick retina. Our experimental system exploits the properties of the promoter for the beta 3 subunit of the neuronal acetylcholine receptors, important components of various phenotypes in the CNS of vertebrates. The beta 3 subunit contributes to define ganglion cell identity in retina and its promoter, whose activation is an early marker of ganglion cell differentiation, is under the specific control of the chick atonal homolog ATH5. Functional analysis of the ATH5 promoter indicates that interactions between ATH5 and several other bHLH transcription factors underlie the patterning of the early retinal neuroepithelium and form a regulatory cascade leading to transcription of the gene for beta 3. ATH5 appears to coordinate the transcriptional pathways that control pan-neuronal properties with those that regulate the subtype-specific features of retinal neurons.

On the transcriptional regulation of neuronal nAChR genes.

The promoters driving transcription of the neuronal nicotinic genes alpha 7 and beta 3 have been characterized in the chicken. Although their regulatory modalities are thoroughly different, they nevertheless lead to co-expression in the same neurons.