Congo red dot test in the early prediction and diagnosis of pre-eclampsia in a tertiary health care centre in India.

OBJECTIVES: To demonstrate the use of urine congophilia quantification in the prediction and diagnosis of pre-eclampsia using Congo red dot test. STUDY DESIGN: A prospective cohort study in 378 consecutive pregnant women was conducted. All eligible, consenting women of gestational age between 10 and 34 weeks were enrolled in the study. The presence of urinary misfolded proteins was screened by a simple dot test technique on unsupported nitrocellulose membrane using Congo red dye. RESULTS: The urinary congophilia was increased in urine from women with pre eclampsia compared to healthy pregnant controls. The mean CRR value of pre eclamptic pregnant women (35.2 ±â€¯9.4%) was five times higher than that of mean CRR value of normotensive pregnant women (6.9 ±â€¯4.7%). The mean gestational age at which Congo red test showed positive was 26.95 ±â€¯2.90 weeks and the time taken from CRD positive to development of PE was 4.92 ±â€¯2.54 weeks of gestation. CONCLUSIONS: In our study, the CRD test was not only effective in predicting pre-eclampsia but was also useful in differentiating between pre-eclampsia and other forms of hypertension, as well as early onset and late onset pre-eclampsia, with positive predictive value of 80.36% and negative predictive value of 92.86.

Characterization of Rubia cordifolia L. root extract and its evaluation of cardioprotective effect in Wistar rat model.

OBJECTIVES: Rubia cordifolia L. (RC) is a well-known and highly valuable medicinal plant in the Ayurvedic system. The present study involves evaluating antioxidant and cardioprotective property of RC root extract. MATERIALS AND METHODS: The characterization of RC root extract was carried out using standard phytochemical and biochemical analysis. The functional groups were analyzed by Fourier transform infrared (FTIR) spectroscopy and phytotherapeutic compounds were identified using high-resolution mass spectrometry (HR-MS). Cardioprotective activity of RC root extract was investigated against cyclophosphamide (CP; 100 mg/kg, i.p)-induced cardiotoxicity in male albino Wistar rats. RC (100, 200, and 400 mg/kg, p.o) or silymarin (100 mg/kg, p.o) was administered immediately after CP on the 1st day and the next consecutive 10 days. Biochemical and histopathological analysis was performed to observe the cardioprotective effects of RC root extract. RESULTS: Phytochemical analysis revealed the presence of secondary metabolites that include alkaloids, flavonoids, saponins, and anthraquinones in RC root extract. FTIR analysis revealed the presence of several functional groups. Based on HR-MS analysis, eight major phytotherapeutic compounds were identified in methanol root extract of RC. Biochemical analysis in CP-induced rat model administered with RC extract revealed significantly enhanced levels of antioxidant markers such as superoxide dismutase, catalase, and glutathione S-transferase. Histopathological study showed that the rat model treated with the root extract had reduced the cardiac injury. CONCLUSION: Our results have shown that the RC extract contains various antioxidant compounds with cardioprotective effect. Treatment with RC root extract could significantly protect CP-induced rats from cardiac tissue injury by restoring the antioxidant markers.

Molecular analysis of PRRT2 gene in a case of paroxysmal kinesigenic dyskinesia patient.

Paroxysmal kinesigenic dyskinesia (PKD) is an abnormal involuntary movement that is episodic or intermittent, with sudden onset, and the attacks are induced by sudden movement. Mutations in proline-rich transmembrane protein 2 (PRRT2) gene have been implicated in the cause of this disorder. This study presents a case of PKD on the basis of clinical findings supported and evidences obtained through a mutational analysis. Sequencing of all the exons of PRRT2 gene revealed a frameshift mutation (p.R217Pfs*8) in exon 2 and a novel transition mutation (c.244C > T) in 5'-untranslated region (UTR). Though mutations in PRRT2 gene are well-established in PKD, this study for the first time presents a novel transition mutation in the exon 2 region.

Necrotizing fasciitis caused by a variant of epidemic methicillin resistant Staphylococcus aureus -15.

We report a case of necrotizing fasciitis (NF), caused by community-acquired epidemic methicillin resistant Staphylococcus aureus 15 (EMRSA 15). The patient had a prolonged recovery period following treatment with antibiotics and surgical debridement of the infected part. Molecular characterization revealed that the isolate carried Staphylococcal Cassette Chromosome mec (SCC mec) type IV harboring Panton-Valentine Leucocidin (pvl) gene and having accessory gene regulator (agr) type I. The isolate was positive for enterotoxin gene cluster (egc). Pulsed field gel electrophoresis patterns revealed that the isolate belonged sequence type 22, which is an Indian variant of EMRSA 15, reported earlier.

Modulation of cellular radiation responses by 2-deoxy-D-glucose and other glycolytic inhibitors: implications for cancer therapy.

BACKGROUND: 2-Deoxy-D-glucose (2-DG), a glycolytic inhibitor, was observed earlier to increase DNA, chromosomal, and cellular damage in tumor cells, by inhibiting energy-dependent repair processes. Lonidamine (LND) selectively inhibits glycolysis in cancer cells. It damages the condensed mitochondria in these cells, impairing thereby the activity of hexokinase (predominantly attached to the outer mitochondrial membranes). It inhibits repair of radiation-induced potentially lethal cellular damage in HeLa and Chinese hamster (HA-1) cells. However, other than a preliminary study on human glioma (BMG-1) cells in this laboratory, the effects of LND on radiation-induced cytogenetic damage have not been reported earlier. AIMS: These studies were carried out to investigate the effects of LND and 2-DG on cell proliferation, viability, and radiation response in the same human glioma cell line, under identical conditions. The respective drug concentrations were selected on the basis of earlier studies. MATERIALS AND METHODS: Human glioma (U373MG) cells were grown in the presence of LND or 2-DG for 2 days. Proliferation response and viability of U373MG human glioma cells were studied by cell counts and uptake of trypan blue dye. Radiosensitization (increase in micronuclei formation) was studied after short-term (4 h postirradiation) drug treatments. OBSERVATIONS: Both the drugs (1) inhibited proliferation response in a concentration-dependent manner; (2) did not induce micronuclei formation in the unirradiated cells; and (3) significantly increased radiation-induced micronuclei formation at nontoxic concentrations. CONCLUSIONS: These data suggest that the short-term presence of either lonidamine or 2-DG-at clinically relevant and nontoxic concentrations-could increase the treatment response of malignant gliomas at optimum radiation doses, reducing thereby the side effects of radiotherapy.

Optimizing radiotherapy of brain tumours by a combination of temozolomide & lonidamine.

BACKGROUND & OBJECTIVE: Temozolomide (TMZ), a second generation alkylating drug, an effective cytotoxic agent as well as radiosensitizer for malignant brain tumours, has side effects like myelosuppression. Lonidamine (LND) increases the effectiveness of several experimental multiple chemotherapy protocols, without increasing bone marrow toxicities and is effective in brain tumour patients. The objective of the present studies was to investigate whether combining clinically relevant doses of LND and TMZ could increase the proliferation and radiation response of malignant human brain tumour cells in vitro. METHODS: A malignant human glioma (U373MG) cell line was used in these studies. TMZ (20, 40 or 60 microM) or LND (100, 150 or 200 microM), or the combination of both (20 and 100 microM, respectively) in 0.1 per cent dimethyl sulphoxide (DMSO) were added three days after setting up cultures, in six well plates (5 x 10(4) cells/ well). The effects of continuous treatment for two days on proliferation response and cytotoxicity were studied after trypsinization; by cell counts and the uptake of trypan blue dye (0.5%). For the study of radiation (60Co-Gamma-rays, 2 Gy) response, drugs were removed 4 h after irradiation and cultures were grown further in drug free, normal growth medium for another 20 h or 44 h. RESULTS: Continuous presence of TMZ or LND for two days significantly inhibited cell proliferation in a concentration dependent manner. The frequencies of non viable cells increased significantly only at higher concentrations of LND. Combination of 20 microM TMZ with 100 microM LND had additive effects on proliferation response, without affecting cell viability. Short-term drug treatments without irradiation did not induce micronuclei formation. Cell proliferation and viability were also not affected. However, post-irradiation presence of either of these drugs for 4 h significantly reduced the proliferation response, 24 and 48 h after treatments. It was further inhibited by the combination treatment. On the contrary, radiation induced micronuclei formation was enhanced by either of the drugs; which was significantly increased by the combined treatment, 24 h as well as 48 h after irradiation. No effects on cell viability were observed, immediately after these treatments as well as at later time points. INTERPRETATION & CONCLUSION: Our findings showed that combination of TMZ and LND at clinically achievable, low plasma concentrations could inhibit tumour growth, and lonidamine could reduce the dose of temozolomide required for radiosensitization of brain tumours.

Procedural success versus clinical risk status in determining discharge of patients after primary angioplasty for acute myocardial infarction.

OBJECTIVES: We evaluated whether patients' clinical status, angioplasty success, or both, should guide discharge after primary angioplasty (i.e., percutaneous coronary intervention [PCI]) for acute myocardial infarction (AMI). BACKGROUND: Current guidelines do not address a discharge strategy for AMI patients undergoing successful PCI. METHODS: Patients who underwent PCI in Primary Angioplasty in Myocardial Infarction (PAMI) studies (N = 3,188) were classified as "high clinical risk" if they had either age >70 years, Killip class >1, heart rate >100 beats/min, systolic blood pressure <100 mm Hg, anterior MI, or left bundle branch block, and as "low clinical risk" if none was present. Successful PCI patients were compared with those with unsuccessful PCI in both groups for 30-day major adverse cardiac events (MACE). RESULTS: Percutaneous coronary intervention was successful in 668 (90%) of 745 low-risk clinical and 2,104 (86%) of 2,443 high-risk clinical patients. Regardless of clinical risk status, patients with successful PCI had lower 30-day MACE than those with unsuccessful PCI (low-risk group: 4.6% vs. 22%, p < 0.0001; high-risk group: 7% vs. 21%; p < 0.0001). Moreover, successful PCI patients with either risk status had few MACE after day 4, whereas unsuccessful PCI patients had more MACE. The success of PCI was the strongest independent predictor of 30-day MACE (odds ratio [OR] 3.7, 95% confidence interval [CI] 2.8 to 5.0). A constellation of three or more high-risk clinical features also predicted higher 30-day MACE (OR 2.25, 95% CI 1.62 to 3.12). CONCLUSIONS: The success of PCI is the prime determinant of clinical outcome after PCI for AMI. The majority of AMI patients with less than three high-risk clinical features who undergo successful PCI may be discharged from the hospital by day 4. In contrast, patients with more than two high-risk clinical features or unsuccessful PCI may need longer observation.

Determination of nickel in alloys and plant leaves with salicylaldehyde 3-oxobutanoylhydrazone by spectrophotometry.

A simple and highly sensitive reagent of salicylaldehyde 3-oxobutanoylhydrazone (salicylaldehyde acetoacetic acid hydrazone, SAAH) was synthesized and studied for the spectrophotometric determination of nickel in detail. In the pH range 6, which greatly increased the selectivity, nickel reacted with SAAH to form a 1:1 yellow complex, having a sensitive absorption peak at 405 nm. Under the optimal conditions, Beer's law was obeyed over the range from 0.0117 to 0.1174 microg cm(-3). The apparent molar absorptivity was 3.025 x 10(5) dm3 mol(-1) cm(-1). The detection limit and the variation coefficient were found to be 1.752 ng cm(-3) and 1.0%, respectively. The method has been applied to the quantitative determination of nickel in different alloys and leaves.