Cannabis-induced impairment of learning and memory

Cannabis sativa preparations are the most commonly used illicit drugs worldwide. The present study aimed to investigate the effect of Cannabis sativa extract in the working memory version of the Morris water maze (MWM; Morris, 1984) test and determine the effect of standard memory enhancing drugs. Cannabis sativa was given at doses of 5, 10 or 20 mg/kg (expressed as Δ^9-tetrahydrocannabinol) alone or co-administered with donepezil (1 mg/kg), piracetam (150 mg/ kg), vinpocetine (1.5 mg/kg) or ginkgo biloba (25 mg/kg) once daily subcutaneously (s.c.) for one month. Mice were examined three times weekly for their ability to locate a submerged platform. Mice were euthanized 30 days after starting cannabis injection when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, glucose and brain monoamines were determined. Cannabis resulted in a significant increase in the time taken to locate the platform and enhanced the memory impairment produced by scopolamine. This effect of cannabis decreased by memory enhancing drugs with piracetam resulting in the most-shorter latency compared with the cannabis. Biochemically, cannabis altered the oxidative status of the brain with decreased MDA, increased GSH, but decreased nitric oxide and glucose. In cannabis-treated rats, the level of GSH in brain was increased after vinpocetine and donepezil and was markedly elevated after Ginkgo biloba. Piracetam restored the decrease in glucose and nitric oxide by cannabis. Cannabis caused dose-dependent increases of brain serotonin, noradrenaline and dopamine. After cannabis treatment, noradrenaline is restored to its normal value by donepezil, vinpocetine or Ginkgo biloba, but increased by piracetam. The level of dopamine was significantly reduced by piracetam, vinpocetine or Ginkgo biloba. These data indicate that cannabis administration is associated with impaired memory performance which is likely to involve decreased brain glucose availability as well as alterations in brain monoamine neurotransmitter levels. Piracetam is more effective in ameliorating the cognitive impairments than other nootropics by alleviating the alterations in glucose, nitric oxide and dopamine in brain

SPARC Ameliorates Ovarian Cancer-Associated Inflammation1

We have recently identified that the role of secreted protein acidic and rich in cysteine (SPARC) in amelioration of peritoneal ovarian carcinomatosis is mediated, at least in part, through mesothelial cell/lysophosphatidic acid-induced inflammatory response in ovarian cancer cells. The aim of this study was to elucidate the molecular mechanisms of the interactions between tumor cells and the cellular components of the ovarian cancer peritoneal microenvironment, specifically, mesothelial cells and macrophages. We found that SPARC not only significantly reduced macrophage chemoattractant protein-1 production and its macrophage chemotactic effect, but also attenuated the response of ovarian cancer cells to the mitogenic and proinvasive effects of macrophage chemo-attractant protein-1 and decreased macrophage-induced cancer cell invasiveness. Overexpression of SPARC in ovarian cancer cells significantly attenuated macrophage- and mesothelial cell-induced production and activity of interleukin-6, prostanoids (prostaglandins E2 and 8-isoprostanes) as well as matrix metalloproteinases and urokinase plasminogen activator. Moreover, the effects of SPARC overexpression in ovarian cancer cells were mediated, in part, through inhibition of nuclear factor-κB promoter activation. These results indicate, for the first time, that the effects of tumor SPARC as a negative regulator of ovarian cancer are mediated through decreased recruitment of macrophages and downregulation of the associated inflammation

Comparison Between Nitazoxanide and Metronidazole in the Treatment of Protozoal Diarrhea in Children

Diarrheal disease is a leading cause of illness and death in children worldwide. Diarrhea is caused by a blend of bacterial, viral and parasitic pathogens. Enteric protozoal infections such as giardiasis, amebiasis and cryptosporidiosis are among the most common and most prevalent forms of gastrointestinal parasitic infections worldwide. Both nitazoxanide and metronidazole are used in treatment of protozoal diarrhea. Nitazoxanide was found to have a very broad spectrum of activity against many forms of parasites. Metronidazole also produces good results when it is used for treatment of parasitic infections. The aim in this study was to evaluate and compare the effect of nitazoxanide and metronidazole in treatment of protozoal diarrhea in children. This study was carried out on 160 diarrheic patients (83 males and 77 females), aged from 1-11 years old collected from the-clinics of pediatric department at Beni suef University Hospital. Patients were divided into two groups. Group A received Nitazoxanide 100 mg in 1-4 years aged patients and 200 mg in 4-11 years aged patients twice daily for 3 days respectively, Group B received Metronidazole 50 mg/Kg/body weight daily for 7 days. Patients were represented to full history taking, physical examination, laboratory investigations in the form of stool analysis, culture and complete blood count (CBC). There was a significant increase in the number of cases resolved by Nitazoxanide compared to Metronidazole group in both amebiasis and giardiasis (p-value < 0.05) with similar clinical improvement when using Nitazoxanide for 3 days and Metronidazole for 7 days. This study confirms the efficacy and safety of nitazoxanide as a 3-day treatment of diarrhea due to giardiasis & amebiasis in children. A 3-day course of nitazoxanide could replace much longer regimens of metronidazole [Med-Science 2014; 3(2.000): 1162-73

SPARC Inhibits LPA-Mediated Mesothelial-Ovarian Cancer Cell Crosstalk

The interplay between peritoneal mesothelial cells and ovarian cancer cells is critical for the initiation and peritoneal dissemination of, and ascites formation in, ovarian cancer. The production of lysophosphatidic acid (LPA) by both peritoneal mesothelial cells and ovarian cancer cells has been shown to promote metastatic phenotype in ovarian cancer. Herein, we report that exogenous addition or ectopic overexpression of the matricellular protein SPARC (secreted protein acidic and rich in cysteine) significantly attenuated LPA-induced proliferation, chemotaxis, and invasion in both highly metastatic SKOV3 and less metastatic OVCAR3 ovarian cancer cell lines. SPARC appears to modulate these functions, at least in part, through the regulation of LPA receptor levels and the attenuation of extracellular signal-regulated kinase (ERK) 1/2 and protein kinase B/AKT signaling. Moreover, our results show that SPARC not only significantly inhibited both basal and LPA-induced interleukin (IL) 6 production in both cell lines but also attenuated IL-6-induced mitogenic, chemotactic, and proinvasive effects, in part, through significant suppression of ERK1/2 and, to a lesser extent, of signal transducers and activators of transcription 3 signaling pathways. Our results strongly suggest that SPARC exerts a dual inhibitory effect on LPA-induced mesothelial-ovarian cancer cell crosstalk through the regulation of both LPA-induced IL-6 production and function. Taken together, our findings underscore the use of SPARC as a potential therapeutic candidate in peritoneal ovarian carcinomatosis

Emergence of Highly Pathogenic Avian Influenza A Virus (H5N1) of Clade 2.3.4.4b in Egypt, 2021–2022

Wild migratory birds have the capability to spread avian influenza virus (AIV) over long distances as well as transmit the virus to domestic birds. In this study, swab and tissue samples were obtained from 190 migratory birds during close surveillance in Egypt in response to the recent outbreaks of the highly pathogenic avian influenza (HPAI) H5N1 virus. The collected samples were tested for a variety of AIV subtypes (H5N1, H9N2, H5N8, and H6N2) as well as other pathogens such as NDV, IBV, ILT, IBDV, and WNV. Among all of the tested samples, the HPAI H5N1 virus was found in six samples; the other samples were found to be negative for all of the tested pathogens. The Egyptian HPAI H5N1 strains shared genetic traits with the HPAI H5N1 strains that are currently being reported in Europe, North America, Asia, and Africa in 2021–2022. Whole genome sequencing revealed markers associated with mammalian adaption and virulence traits among different gene segments, similar to those found in HPAI H5N1 strains detected in Europe and Africa. The detection of the HPAI H5N1 strain of clade 2.3.4.4b in wild birds in Egypt underlines the risk of the introduction of this strain into the local poultry population. Hence, there is reason to be vigilant and continue epidemiological and molecular monitoring of the AIV in close proximity to the domestic–wild bird interface