"Spice" (Synthetic Marijuana) Induced Acute Myocardial Infarction: A Case Series.

Marijuana is the most widely abused "recreational" substance in the United States, with highest prevalence in young adults. It is reported to cause ischemic strokes, hepatitis, anxiety, and psychosis. Although it is associated with dose dependent tachycardia and can lead to coronary vasospasm, it has not been directly related to acute myocardial infarction (AMI). Marijuana induced coronary vasospasm can result in endothelial denudation at the site of a vulnerable atherosclerotic plaque in response to hemodynamic stressors, potentially causing an AMI. Spice refers to herbal mixture with composition and effects similar to that of marijuana and therefore is referred to as "synthetic marijuana." Herein, we report 3 cases of spice induced ST-segment elevation myocardial infarction. All patients were relatively young and had few or absolutely no risk factors for cardiovascular disease. All patients underwent emergent coronary angiography, with two needing stent placement and the third requiring only aspiration thrombectomy. Our case series emphasizes the importance of suspecting and investigating synthetic marijuana use in low risk young adults presenting with AMI.

Detection of serum cytokines before and after pharmacological and surgical treatment in patients with cystic echinococcosis.

Human cystic echinococcosis (CE), caused by Echinococcus granulosus, is one of the most important and widespread parasitic zoonoses. One of the problems that can be encountered after treating CE patients is the risk of post-surgical relapses or treatment failure, thus a long-term clinical and serological follow-up is required to evaluate the success or failure of therapy. In the present study immunological markers have been identified to indicate the effectiveness of pharmacological and surgical treatments. The relationship between serum cytokine levels and the outcome of chemotherapy and surgery was evaluated in 50 patients with CE. Serum interleukin (IL)-4, IL-10 and interferon-gamma (IFN-γ) concentrations were determined by enzyme-linked immunosorbent assay (ELISA) before and after pharmacological and surgical treatment. Serum cytokine levels of IL-4, IL-10 and IFN-γ were elevated in a significant proportion of patients during the active stage of disease. IL-4, IL-10 and IFN-γ were measurable in 41 (82%), 37 (74%) and 25 (50%) patients before the treatment. Clinical and radiological assessment of patients 2 years after pharmacological treatment has shown that 48 of 50 patients responded to treatment. IL-4 and IL-10 levels were decreased significantly (P< 0.05) in these patients. Conversely, patients who did not respond showed high levels of IL-4 and IL-10 and undetectable levels of IFN-γ. Hence these results suggest that serum IL-4 and IL-10 detection may be useful in the follow-up of patients with CE.

Effect of psychosine on inducible nitric-oxide synthase expression under different culture conditions: implications for Krabbe disease.

BACKGROUND AND OBJECTIVES: Krabbe disease is a neuro-inflammatory disorder in which galactosyl sphingosine (psychosine) accumulates in nervous tissues. Despite some leads in elucidating the mechanism of psychosine action on different cells of brain, there still remain gaps in the knowledge and mechanisms behind events in the pathogenic cascade of Krabbe disease. Inflammation in the brain in Krabbe disorder is an important factor in neural damage. This study was undertaken to access the role of psychosine in the regulation of nitric oxide (NO) and inducible nitric oxide synthase (iNOS), i.e., inflammatory markers, under two different conditions viz., using a single cell line and using primary mixed glial cells. MATERIALS AND METHODS: BV2 murine microglial cells and murine primary mixed glial cells were used during this study. The cell lines, after 12 hr serum starvation, were treated with lipopolysaccharide (LPS) at 25 ng/ml in the absence or presence of increasing concentrations of psychosine (5, 10 and 15 microM). Formation of NO was estimated using Greiss reagent, and expression of iNOS was done by SDS-page followed by western blotting using anti-iNOS antibody. RESULTS: In BV2 cells it was found that LPS (25 ng/ml) treatment, induced production of NO, but the LPS induced NO production was inhibited when LPS was used in combination with psychosine. This result was corroborated by parallel trend seen in iNOS expression under same conditions. Contrary to this, LPS (25 ng/ml) induced production of NO in primary mixed glial cells was dose dependently enhanced when LPS was used in combination with psychosine (5, 10 and 15 microM). This result was also corroborated by iNOS expression under same experimental conditions. DISCUSSION: This study suggests that in-vitro data obtained using individual cell lines may not reflect the actual complex intricacies involved in development of Krabbe brain pathology. And that the effect of psychosine in Krabbe brain may be modulated by presence of LPS or other pro-inflammatory stimuli in the brain of these children, e.g., after an infection.

Long dose exposure of hydrogen peroxide (H2O2) in albino rats and effect of Podophyllum hexandrum on oxidative stress.

OBJECTIVES: The effect of Podophyllum hexandrum methanolic extract and alpha-tocopherol in reducing oxidative stress in male albino rats was evaluated. MATERIALS AND METHODS: Lipid peroxidation was monitored by measuring malondialdehyde (MDA) level in different tissues of rats. Activities of free radical scavenging enzymes (superoxide dismutase, glutathione peroxidase and catalase) were determined using H2O2 decomposition. RESULTS: Results showed that administration of H2O2 (0.1%) in drinking water of the rats, for 25 weeks, increased the malondialdehyde levels in liver, kidney and lung tissues of all the rats. However, rats receiving Podophyllum hexandrum extract and alpha-tocopherol had lower MDA levels in a dose dependent manner, which indicates decreased lipid peroxidation in these rats. Increase in the catalase activity appears to be a response to H2O2 accumulation. The decrease in the activity of catalase and increase in the activity of superoxide dismutase and glutathione peroxidase in different organs of the rats receiving Podophyllum hexandrum extract and alpha-tocopherol indicates the protective effect of the plant in combating oxidative stress undergone by the rats. OBJECTIVES: Rhizome of Podophyllum hexandrum have been ethnomedically claimed to possess a wide array of biological activities including anticancer activity. MATERIALS AND METHODS: To verify the folklore claim, this study was performed in a six Human carcinoma cell lines, Lung (A-549), Prostate (PC-3), Colon (Colo-25), Breast (MCF-7), Neuroblastoma (IMR-32) and CNS (SF-295) MCF-7 and MDA-MB-231. RESULTS: Methanol and 70% ethanolic extracts of the rhizome of Podophyllum hexandrum showed highest cytotoxic effect on MCF-7 (Breast) and Colo-25 (Colon) cell line, as determined with sulforhodamine-B (SRB) assay. CONCLUSIONS: These findings 1 - showed that Podophyllum hexandrum extract may ameliorate H2O2 induced oxidative stress by decreasing lipid peroxidation via alteration of the antioxidant defense system of the rats. 2 - these data also showed the anticancer activity of the plant extracts on different human cancer cell lines. However, further investigation is needed to assess the molecular mechanisms mediated anticancer activities of this plant.

Spin filtering of hot holes in a metallic ferromagnet.

Spin-dependent transport of nonequilibrium holes in ferromagnetic thin films and trilayers is investigated using ballistic hole magnetic microscopy. For Co, the hole attenuation length is short and increases from 6 to 10 A in the energy range 0.8 to 2 eV. The hole transmission of a Ni(81)Fe(19)/Au/Co trilayer is clearly spin dependent, resulting in a surprisingly large current change by a factor of 2.3 in a magnetic field. The energy and spin dependence of the hole transmission cannot be explained by the phase space available for inelastic decay of the hot holes.

Purification of diacylglycerol kinase from Microsporum gypseum and its phosphorylation by the catalytic subunit of protein kinase A.

Diacylglycerol (DG) kinase (EC 2.7.1.107) was purified to homogeneity from the soluble extract of Microsporum gypseum, a dermatophyte. Purified enzyme showed a final specific activity of 2172 pmol/min/mg protein and its apparent molecular weight on SDS-PAGE was found to be 93 kDa. The activity of purified enzyme was inhibited in a dose-dependent manner in the presence of DG-kinase inhibitor (D5919, Sigma). DG-kinase activity was found to be stimulated in the presence of phosphatidylcholine, phosphatidylethanolamine, and cardiolipin while the activity was alleviated in the presence of phosphatidic acid and arachidonic acid. Kinase activity was partially inhibited when assayed after prior treatment with alkaline phosphatase. Treatment of DG-kinase with the catalytic subunit of protein kinase A (PKA)-stimulated DG-kinase activity in a dose-dependent manner. Incubation of DG-kinase with the catalytic subunit of PKA led to the phosphorylation of DG-kinase as revealed by autoradiography. The phosphorylated band disappeared completely in the presence of specific PKA inhibitor. Increased activity of DG-kinase on incubation with the catalytic subunit of PKA was possibly due to the phosphorylation of the former by the latter. Whether this in vitro phosphorylation and activation of DG-kinase occurs under physiological conditions remains to be elucidated.

Purification and characterization of cAMP dependent protein kinase from Microsporum gypseum.

A cyclic AMP dependent protein kinase (PKA), its regulatory (R) and catalytic (C) subunits were purified to homogeneity from soluble extract of Microsporum gypseum. Purified enzyme showed a final specific activity of 277.9 nmol phosphate transferred min(-1) mg protein(-1) with kemptide as substrate. The enzyme preparation showed two bands with molecular masses of 76 kDa and 45 kDa on sodium dodecyl polyacrylamide gel electrophoresis. The 76 kDa subunit was found to be the regulatory (R) subunit of PKA holoenzyme as determined by its immunoreactivity and the isoelectric point of this subunit was 3.98. The 45 kDa subunit was found to be the catalytic (C) subunit by its immunoreactivity and phosphotransferase activity. Gel filtration using Sepharose CL-6B revealed the molecular mass of PKA holoenzyme to be 240 kDa, compatible with its tetrameric structure, consisting of two regulatory subunits (76 kDa) and two catalytic subunits (45 kDa). The specificity of enzyme towards protein acceptors in decreasing order of phosphorylation was found to be kemptide, casein, syntide and histone IIs. Purified enzyme had apparent K(m) values of 71 microM and 25 microM for ATP and kemptide, respectively. Phosphorylation was strongly inhibited by mammalian PKA inhibitor (PKI) but not by inhibitors of other protein kinases. The PKA showed maximum activity at pH 7.0 and enzyme activity was inhibited in the presence of N-ethylmaleimide (NEM) which shows the involvement of sulfhydryl groups for the activity of PKA. PKA phosphorylated a number of endogenous proteins suggesting the multifunctional role of cAMP dependent protein kinase in M. gypseum. Further work is under progress to identify the natural substrates of this enzyme through which it may regulate the enzymes involved in phospholipid metabolism.