scholarly journals Lentivirus Mediated siRNA against GluN2B Subunit of NMDA Receptor Reduces Nociception in a Rat Model of Neuropathic Pain

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Feixiang Wu ◽  
Ruirui Pan ◽  
Jiaying Chen ◽  
Megumi Sugita ◽  
Caiyang Chen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Chronic Constriction Injury ◽  
Term Treatment ◽  
Prolonged Treatment ◽  
Small Interference Rna ◽  
Study Results ◽  
Long Term Treatment ◽  
Mrna And Protein Expression ◽  
Promising Treatment

Although neuropathic pain (NP) is still not fully understood by scientists and clinicians alike, studies suggest that N-methyl-D-aspartate (NMDA) receptors play an important role in the induction and maintenance of NP. A promising treatment for NP is through the downregulation of NMDA subunit GluN2B by RNA interference; however, naked siRNA (small interference RNA) is not effective in long-term treatments. In order to concoct a viable prolonged treatment for NP, Lv-siGluN2B (lentivirus carrying siRNA targeting GluN2B subunit) was prepared and the antinociception effects were observed in chronic constriction injury (CCI) rats in the present study. Results showed that Lv-siGluN2B was transduced into spinal cord cells after intrathecal injections and effectively reduced the nociception induced by sciatic nerve ligation while inhibiting the mRNA and protein expression of GluN2B. This antinociception effect lasted approximately 7 weeks. These findings suggest that GluN2B subunit could be a target for NP treatment and Lv-siGluN2B represents a new potential option for long-term treatment of NP.

JAK1-dependent transphosphorylation of JAK2 limits the antifibrotic effects of selective JAK2 inhibitors on long-term treatment

2017 ◽  
Vol 76 (8) ◽  
pp. 1467-1475 ◽  
Author(s):  
Yun Zhang ◽  
Ruifang Liang ◽  
Chih-Wei Chen ◽  
Tatjana Mallano ◽  
Clara Dees ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Chronic Treatment ◽  
Term Treatment ◽  
Janus Kinase ◽  
Prolonged Treatment ◽  
Therapeutic Effects ◽  
Long Term Treatment ◽  
Jak2 Inhibition ◽  
Jak2 Inhibitors

ObjectivesJanus kinase 2 (JAK2) has recently been described as a novel downstream mediator of the pro-fibrotic effects of transforming growth factor-β. Although JAK2 inhibitors are in clinical use for myelodysplastic syndromes, patients often rapidly develop resistance. Tumour cells can escape the therapeutic effects of selective JAK2 inhibitors by mutation-independent transactivation of JAK2 by JAK1. Here, we used selective JAK2 inhibition as a model to test the hypothesis that chronic treatment may provoke resistance by facilitating non-physiological signalling pathways in fibroblasts.MethodsThe antifibrotic effects of long-term treatment with selective JAK2 inhibitors and reactivation of JAK2 signalling by JAK1-dependent transphosphorylation was analysed in cultured fibroblasts and experimental dermal and pulmonary fibrosis. Combined JAK1/JAK2 inhibition and co-treatment with an HSP90 inhibitor were evaluated as strategies to overcome resistance.ResultsThe antifibrotic effects of selective JAK2 inhibitors on fibroblasts decreased with prolonged treatment as JAK2 signalling was reactivated by JAK1-dependent transphosphorylation of JAK2. This reactivation could be prevented by HSP90 inhibition, which destabilised JAK2 protein, or with combined JAK1/JAK2 inhibitors. Treatment with combined JAK1/JAK2 inhibitors or with JAK2 inhibitors in combination with HSP90 inhibitors was more effective than monotherapy with JAK2 inhibitors in bleomycin-induced pulmonary fibrosis and in adTBR-induced dermal fibrosis.ConclusionFibroblasts can develop resistance to chronic treatment with JAK2 inhibitors by induction of non-physiological JAK1-dependent transactivation of JAK2 and that inhibition of this compensatory signalling pathway, for example, by co-inhibition of JAK1 or HSP90 is important to maintain the antifibrotic effects of JAK2 inhibition with long-term treatment.

scholarly journals Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients

2017 ◽  
Vol 78 (5-6) ◽  
pp. 320-329 ◽  
Author(s):  
Sebastian Schimrigk ◽  
Martin Marziniak ◽  
Christine Neubauer ◽  
Eva Maria Kugler ◽  
Gudrun Werner ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Treatment Option ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Pain Patients

DESOXYRIBONUCLEIC ACID SYNTHESIS (DNA) IN THE RAT OVARY AFTER TREATMENT WITH ORAL CONTRACEPTIVES

1968 ◽  
Vol 59 (1) ◽  
pp. 49-52 ◽  
Author(s):  
U. Mohr ◽  
G. Seene ◽  
A. Emminger ◽  
J. Althoff ◽  
F. Zimmer
Keyword(s):  
Acid Synthesis ◽  
Term Treatment ◽  
Organ Weight ◽  
Prolonged Treatment ◽  
Activity Measurement ◽  
Desoxyribonucleic Acid ◽  
Long Term Treatment ◽  
Rat Ovary ◽  
Cycle Dependent

ABSTRACT The radioactively labelled ovaries of Wistar rats were examined by autoradiography and activity measurement after long-term treatment of varying duration with an oral contraceptive (Lyndiol®). The administration of Lyndiol® led to the absence of the normal oestrous cycle and, after more prolonged treatment, to a reduction both in the number and size of follicles and to atrophy of the ovaries. As calculated per 1 mg dry organ weight, the DNA values found were within the range of the cycle-dependent fluctuations; however, they were a great deal lower when the reduced organ weight was taken into account.

scholarly journals Long-term treatment with the dopamine agonist quinagolide of patients with clinically non-functioning pituitary adenoma

2000 ◽  
pp. 615-621 ◽  
Author(s):  
FR Nobels ◽  
WW de Herder ◽  
WM van den Brink ◽  
DJ Kwekkeboom ◽  
LJ Hofland ◽  
...  
Keyword(s):  
Dopamine Agonist ◽  
Tumor Volume ◽  
Term Treatment ◽  
Alpha Subunit ◽  
Prolonged Treatment ◽  
Visual Field Defects ◽  
Entire Treatment Period ◽  
Long Term Treatment ◽  
Serum Gonadotropin

OBJECTIVE: This study was performed to evaluate the effect of prolonged treatment with the dopamine agonist quinagolide on serum gonadotropin and alpha-subunit concentrations and tumor volume in patients with clinically non-functioning pituitary adenomas (CNPA). DESIGN: Ten patients with CNPA were treated with quinagolide (0.3 mg daily). The median duration of treatment was 57 months (range 36-93 months). Blood samples for measurement of serum gonadotropin and alpha-subunit concentrations were drawn before treatment, after 5 days, and at each outpatient visit. Computerized tomography or magnetic resonance imaging of the pituitary region and Goldmann perimetry were done before and at regular intervals during treatment. RESULTS: A significant decrease of serum FSH, LH or alpha-subunit concentrations was found in nine patients. The levels remained low during the entire treatment period. In two out of three patients with pre-existing visual field defects a slight improvement was shown during the first months of treatment, but eventually deterioration occurred in all three patients. A fourth patient developed unilateral ophthalmoplegia during treatment. During the first year tumor volume decreased in three patients, but in two of them regrowth occurred after a few months. In six patients progressive tumor growth occurred despite sustained suppression of gonadotropin or alpha-subunit levels. CONCLUSIONS: Long-term treatment of patients with CNPA with high doses of the dopamine agonist quinagolide could not prevent progressive increase in tumor size in most patients. It remains unproven whether quinagolide retards CNPA growth. Additional studies are needed to investigate whether subgroups of patients, e.g. those with positive dopamine receptor scintigraphy or those with marked hypersecretion of intact gonadotropins or subunits, will respond more favorably to treatment with dopamine agonists.

Long-term treatment of neuropathic pain with a 5% lidocaine medicated plaster

2010 ◽  
Vol 27 (2) ◽  
pp. 169-173 ◽  
Author(s):  
Ilca Ricarda Wilhelm ◽  
Alexander Tzabazis ◽  
Rudolf Likar ◽  
Reinhard Sittl ◽  
Norbert Grieinger
Keyword(s):  
Neuropathic Pain ◽  
Term Treatment ◽  
Long Term Treatment

scholarly journals Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer Pain

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ruirui Pan ◽  
Huiting Di ◽  
Jinming Zhang ◽  
Zhangxiang Huang ◽  
Yuming Sun ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Pain Treatment ◽  
Intrathecal Injection ◽  
Bone Cancer ◽  
Bone Cancer Pain ◽  
Prolonged Treatment ◽  
Small Interference Rna ◽  
Long Term Treatment ◽  
Walker 256

Although bone cancer pain is still not fully understood by scientists and clinicians alike, studies suggest that toll like receptor 4 (TLR4) plays an important role in the initiation and/or maintenance of pathological pain state in bone cancer pain. A promising treatment for bone cancer pain is the downregulation of TLR4 by RNA interference; however, naked siRNA (small interference RNA) is not effective in long-term treatments. In order to concoct a viable prolonged treatment for bone cancer pain, an inducible lentivirus LvOn-siTLR4 (tetracycline inducible lentivirus carrying siRNA targeting TLR4) was prepared and the antinociception effects were observed in bone cancer pain rats induced by Walker 256 cells injection in left leg. Results showed that LvOn-siTLR4 intrathecal injection with doxycycline (Dox) oral administration effectively reduced the nociception induced by Walker 256 cells while inhibiting the mRNA and protein expression of TLR4. Proinflammatory cytokines as TNF-αand IL-1βin spinal cord were also decreased. These findings suggest that TLR4 could be a target for bone cancer pain treatment and tetracycline inducible lentivirus LvOn-siTLR4 represents a new potential option for long-term treatment of bone cancer pain.

A longitudinal study of psychotropic drug prescription

1982 ◽  
Vol 12 (1) ◽  
pp. 201-206 ◽  
Author(s):  
P. Williams ◽  
J. Murray ◽  
A. Clare
Keyword(s):  
Longitudinal Study ◽  
Psychotropic Drug ◽  
Drug Prescription ◽  
Term Treatment ◽  
Psychological Morbidity ◽  
Prolonged Treatment ◽  
Cross Sectional ◽  
Long Term Treatment ◽  
Cross Sectional Studies

SynopsisWhile many of the characteristics of psychotropic drug consumers have been established by means of cross-sectional studies, little is known about new consumers and the factors which predispose to long-term treatment. We report on a longitudinal study of 153 general practice patients beginning a new course of psychotropic drug treatment and characterized by extensive physical and psychological morbidity. About 1 in 5 were still receiving psychotropic drugs 6 months later and this prolonged treatment was associated with increased age, previous psychotropic drug-use, higher levels of psychological morbidity at the inception of treatment and, for the women only, social problems as perceived by the general practitioners.

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