Effect of Single Acupuncture Point (Liver 7) on Pain and Range of Motion on Osteoarthritis of Knee.

Background: : Osteoarthritis of the knee (OAK) is a chronic degenerative musculoskeletal disorder that strongly affects the elderly population and decreases their quality of life. Pain, stiffness, and restricted knee movements are the major characteristic features of OAK. There are no studies available on the effect of the liver 7 (LR 7) acupuncture point on pain and range of motion. Objectives: : To study the effectiveness of the LR 7 acupuncture point on pain and range of motion in chronic OAK patients. Methods: : Thirty-five subjects aged between 40 and 65 years were recruited from Government Yoga and Naturopathy Medical College, Chennai. Participants were included in the study after they fulfilled the eligibility criteria. The duration of acupuncture was 20 minutes (5 days/week) for 2 weeks. Baseline and post-intervention assessments were performed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the degree of knee flexion and extension was measured using a goniometer. Results: : Pre- and post-trial outcomes were compared using paired t-tests. LR 7 acupuncture reduced the WOMAC score from 49 to 30 (p < 0.001), indicating that pain was alleviated. Treatment increased the range of knee flexion from 110 to 115 degrees and reduced knee extension (p < 0.01) from 16 to 9 degrees (p < 0.001). These findings indicate that acupuncture treatment improved the range of knee movement. Conclusion: : The present study showed that 10 sessions of LR 7 acupuncture for people with OAK significantly reduced pain and increased range of motion. We conclude that LR 7 acupuncture is an adjuvant therapy for alleviating pain and managing OAK.

Oxytocin: effects of degradation on radioimmunologic and biologic activity.

Incubation with thioglycollate destroyed biologic activity of oxytocin, but left immunologic activity intact. Incubation with plasma of pregnant women at term or with placental extract destroyed biologic and immunologic activities. Dissociation of biologic from immunologic sites is suggested.

Molecular cloning and characterization of the promoter region of murine natural killer cell receptor 2B4.

Natural killer (NK) cells are bone marrow-derived lymphocytes that have the ability to kill certain tumor cells and virally infected cells. The activation of NK cells is mediated by a balance of negative and positive signals from cell-cell interactions and from responses to cytokines. However, the molecular basis of NK cell activation and recognition of target cells is poorly understood. We have previously identified, cloned and characterized a receptor, 2B4, expressed on murine NK cells. 2B4 is not only expressed on all NK cells, but also on a subset of T-cells which have NK-like killing properties. Structural analysis indicated that 2B4 belongs to the CD2 subset of immunoglobulin superfamily. We have also shown 2B4 to interact with CD48 with nine times more affinity than that of CD2-CD48 interaction. In order to understand the transcriptional regulation as well as the mechanisms controlling the restricted expression of the 2B4 gene, we obtained a genomic 2B4 clone including the sequence of the 5'-flanking region. To define the start site of transcription, we performed primer extension and 5'-RACE assays and found that the 2B4 gene may be initiated at multiple start sites and driven by a TATA-less promoter. Transient transfections of nested 5'-fragments of the 2B4 promoter to drive CAT expression revealed tissue specific expression in CTLL-2 cells, a mouse T-cell line. A promoter fragment of 348 bases upstream from the first base of the mouse 2B4 cDNA clone p2B4.8 produced maximal CAT activity in CTLL-2 cells. The presence of the region -653 to -540 on the other hand, drastically reduced transcription. Sequence analysis of this promoter region has identified potential recognition motifs for a number of lymphocyte-restricted in addition to ubiquitous transcription factors, which may play a role in the transcriptional regulation of the mouse 2B4 gene.

Antidiabetic and antihyperlipemic effects of Clemeo felina.

Petroleum ether and benzene extracts of Clemeo felina, given orally at doses of 300 mg kg(-1) day(-1) for 30 days, were found to be antidiabetic and antihyperlipemic on alloxan diabetic rats. Moreover, a significant decrease in the activities of serum enzymes like alkaline phosphatase, acid phosphatase and HMGCoA reductase activity in the liver was observed. However, treatment of rats with the extracts as well as standard antidiabetic drugs increased liver hexakinase activity and serum LDH activity.

Molecular characterization of the rat NK cell receptor 2B4.

2B4 (CD244) is a cell surface glycoprotein of the immunoglobulin superfamily involved in the regulation of natural killer and T lymphocyte function. It is the high affinity counter-receptor for CD48. In mouse and human NK cells, crosslinking of 2B4 with a specific monoclonal antibody or with CD48 can trigger cell-mediated cytotoxicity, IFN-gamma secretion, phosphoinositol turnover and NK cell invasiveness. Recent reports of defective 2B4 signaling and NK cell function in X-linked lymphoproliferative syndrome suggest that this may contribute to the progression of this human disease. Here we describe the molecular characterization of the rat 2B4 gene. The cDNA encodes a protein of 395 amino acid residues that contain two Ig domains in the extracellular region and three unique tyrosine motifs (TxYxxV/I/A) in the cytoplasmic region. The predicted protein has 81 and 68% similarity with mouse 2B4 and human 2B4, respectively. Additionally, it has 94 and 89% similarity at the protein level with the recently reported rat 2B4 related genes, r2B4R-tm and r2B4R-se respectively. Northern blot analysis indicated the presence of multiple transcripts in rat LAK cells and RNK-16 cells. Immunoprecipitation and deglycosylation studies showed that rat 2B4 is glycosylated to similar extent as that of mouse and human 2B4. The cloning of r2B4 in the light of the availability of rat NK cell lines should facilitate in vitro and in vivo experiments to decipher the functional role of 2B4 in NK cell biology.

Oxytocin in maternal and fetal blood.

Radioimmunoassayable plasma oxytocin (OT) has been measured in maternal and fetal blood. Simultaneous samples were obtained in maternal forearm venous blood and in umbilical venous and arterial blood in 29 patients at term delivery. In addition, maternal forearm venous blood samples were also obtained 10 minutes prior to delivery. Mean OT level in maternal plasma at delivery was 82 +/- 12 muU/ml, and at 10 minutes prior to delivery the mean OT level was 90 +/- 11 muU/ml. The umbilical arterial plasma OT showed 95 +/- 12 muU/ml and the umbilical vein plasma OT was 60 +/- 10 muU/ml. Oxytocin levels higher in maternal blood than in fetal blood were found with the following incidence: In 51% of samples there was more OT in maternal venous blood than in umbilical arterial blood, and in 84% of samples there was more OT in maternal blood than umbilical vein blood. During the postpartum period, the mean maternal plasma OT was 66 +/- 8 muU/ml for the first day, and 50 +/- 9 muU/ml and 54 +/- 9 muU/ml for the second and third days, respectively. This study indicates that both the fetus and the mother are active producers of oxytocin.

Plasma oxytocin concentrations in a pregnant woman with total vasopressin deficiency.

Plasma concentrations of oxytocin and vasopressin were determined by radioimmunoassay in a woman with clinical diabetes insipidus. Plasma oxytocin levels were normal and ranged from less than 0.25 microU/ml to 76 microU/ml during the last month of pregnancy and during spontaneous labor. Vasopressin requirements did not change during pregnancy. Unexplained vasopressin resistance and massive diuresis occurred early in the postpartum period. Plasma vasopressin concentrations were undetectable in the nonpregnant state. The documentation of normal oxytocin production and total vasopressin deficiency suggests that an anatomic defect is unlikely to cause this disorder unless it is limited to axons and cell bodies containing vasopressin and not oxytocin.

Plasma oxytocin concentrations in cyclic mares and sexually aroused stallions.

An experiment was conducted to measure plasma oxytocin concentrations at 4 different stages of the estrous cycle in 11 pony mares. Plasma oxytocin concentrations (muU/ml +/- SE) were found to be higher (P<.01) on day 2 of estrous (39.8 +/- 12.5) and day 5 post-ovulation (33.1 +/- 12.0) than on day 10 (2.3 +/- 1.6) and day 15 post-ovulation (6.8 +/- 4.1). A second experiment was conducted to measure jugular plasma oxytocin concentrations before and after sexual arousal in six pony stallions. Oxytocin concentrations (muU/ml +/- SE) were higher (P<0.06) after sexual arousal (50.5 +/- 8.9) than before sexual arousal (23.8 +/- 2.9). These data suggest plasma oxytocin concentrations may be associated with ovarian function in mares and with sexual behavior in stallions.

Human ovulation and plasma oxytocin.

Plasma oxytocin (OT) concentrations were measured by radioimmunoassay (RIA) method without extracting plasma in 11 normal menstruating women. Mean plasma OT level began to increase steadily from the 7th day of the menstrual cycle and this level rose up to 20 +/- 5 microU/ml (Mean +/- S.E.) on the 10th day of the cycle. OT level declined to 13 +/- 6 microU/ml on the day of LH peak and continuously declined for another 2 days - then rose. The OT level was higher during the follicular phase than during the luteal phase. In 1 individual OT measured in 2 cycles a year apart showed the highest level of OT coincided with LH and FSH peak and abruptly declined. When there was the highest level of progesterone, the OT level was measurable 1 out of 11 cycles. From this study, we conclude that OT may have a role in human ovulation either synergistically or alone with other ovulatory mechanisms and ovarian estradiol and progesterone control the secretion of OT and also suggests that OT may play some role in the regulation of the luteolysis and the menstrual cycle in women.

Glucose-6-phosphate dehydrogenase deficiency and malaria--a study on north Madras population.

Blood samples from 381 healthy individuals and 236 malaria patients residing in North Madras were studied for glucose-6-phosphate dehydrogenase deficiency. The incidence of this deficiency in this area was found to be 10.05%. Partially deficient healthy females showed a protective trend against malarial infection with the Chi-squared test approaching statistical significance.

Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor.

Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a 'wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model.

A novel peptide inhibitor attenuates C-reactive protein's pro-inflammatory effects in-vivo.

BACKGROUND: Higher levels of C-reactive protein (CRP) predict cardiovascular events and also portend a poorer prognosis in patients with acute coronary syndromes. Much in-vitro and in-vivo data support a role for CRP in atherogenesis. METHODS: Using the one-bead-one-compound (OBOC) combinatorial library method we have successfully identified peptides against human CRP that inhibit its biological effects in-vitro. Hence we tested the effect of the best characterized inhibitor (CRP-i2) on the effects of CRP in an appropriate animal model, Wistar rats. RESULTS: Treatment with CRP resulted in significant increase in superoxide anion, nuclear factor kappaB (NFκb) activity and the release of biomarkers of inflammation from macrophages compared to Wistar rats treated with human albumin (HuSA). Pre-treatment with the inhibitor, CRP-i2, resulted in a significant reduction in CRP induced superoxide anion, NFκb activity and biomarkers of inflammation. Also, there were no observed clinical or laboratory related adverse effects. CONCLUSIONS: We demonstrate that our novel peptide inhibitor attenuates the proinflammatory effects of CRP in-vivo. Future studies will examine the long-term effects of this inhibitor on vascular pathobiology.

Neuropharmacological activity of Lippia nodiflora Linn.

INTRODUCTION: In the recent years, plants containing flavonoids have gained much more interest in research area, as they are found to be specific ligands for benzodiazepine receptors. MATERIAL AND METHODS: In our investigation, we evaluated the neuropharmacological profile of petroleum, chloroform and ethanolic extracts of aerial part of Lippia nodiflora Linn. With experimental models using test such as potentiation of diazepam-induced sleeping time, locomotor activity, motor coordination, exploratory behavior pattern, elevated plus maze and maximal electroshock convulsions. Diazepam at doses of 5, 4, and 1 mg/kg served as standard. RESULTS: Results showed that the ethanolic extract of L. nodifl ora at both doses (250 and 500 mg/kg p.o.) and its chloroform extract at a higher dose of 500 mg/kg produced central inhibitory (sedative) effects, anticonvulsant effect and anxiolytic effect in mice. Values were statistically significant (P < 0.05 and P < 0.01) when compared to the control group. The petroleum ether extract of plant at both dose levels (250 and 500 mg/kg p.o.) did not produce any central effects. CONCLUSION: In conclusion, we can say that the ethanolic and chloroform extracts showed the central inhibitory activity due to the presence of fl avonoids and this fact was also supported by the finding that the petroleum ether extract did not show any central effect and flavonoids were not found in it.

The haematology of Plasmodium vivax before and after chloroquine and primaquine treatment in north Madras area.

Changes in haematological parameters were studied in 35 Plasmodium vivax infected patients and compared with those in an equal number of normal subjects. Patients showed a high proportion of schizonts of P. vivax (1-2%). Hb, PCV and RBC values were significantly decreased (p less than 0.001) with increasing parasitaemia. Osmotic fragility was slightly increased (15%) when compared to controls and ranged from 0.385-0.405 (50% hypo-osmotic haemolysis given at gm/dl of NaCl) with increasing parasitaemia in the patients. Decreased levels of lymphocyte and increased levels of eosinophils and monocytes were seen in P. vivax infected patients. However, after treatment with chloroquine and primaquine, all the haematological parameters were restored to near normal levels.