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2.
Nat Commun ; 10(1): 4103, 2019 Sep 05.
Article in English | MEDLINE | ID: mdl-31488829

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

3.
Nat Commun ; 10(1): 3121, 2019 07 16.
Article in English | MEDLINE | ID: mdl-31311923

ABSTRACT

Increasing the potential of soil to store carbon (C) is an acknowledged and emphasized strategy for capturing atmospheric CO2. Well-recognized approaches for soil C accretion include reducing soil disturbance, increasing plant biomass inputs, and enhancing plant diversity. Yet experimental evidence often fails to support anticipated C gains, suggesting that our integrated understanding of soil C accretion remains insufficient. Here we use a unique combination of X-ray micro-tomography and micro-scale enzyme mapping to demonstrate for the first time that plant-stimulated soil pore formation appears to be a major, hitherto unrecognized, determinant of whether new C inputs are stored or lost to the atmosphere. Unlike monocultures, diverse plant communities favor the development of 30-150 µm pores. Such pores are the micro-environments associated with higher enzyme activities, and greater abundance of such pores translates into a greater spatial footprint that microorganisms make on the soil and consequently soil C storage capacity.


Subject(s)
Biomass , Carbon Cycle , Microbiota/physiology , Soil Microbiology , Atmosphere/chemistry , Biodiversity , Carbon/metabolism , Carbon Dioxide/metabolism , Plant Roots , Plants , Soil/chemistry
4.
Drug Res (Stuttg) ; 66(6): 330-6, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27022719

ABSTRACT

BACKGROUND: Over the past several years, the considerable attention has been progressively given to liposomal formulations of anthracyclines. SinaDoxosome(®) (Exir Nano Sina Company, Iran) is a pegylated liposomal doxorubicin (DOX) which approved by Food and Drug Administration of IRAN for treatment of some types of cancer. The aim of this study was to compare the biodistribution, efficacy, cardiotoxicity and hepatotoxicity of SinaDoxosome(®) with Caelyx(®) in mice bearing C-26 colon carcinoma. METHODS AND RESULTS: Mice tumor size evaluation during the experimental period (28 days) showed comparable therapeutic efficacy of nano-formulations. The biodistribution studies showed no significant difference in DOX tissue concentration between Caelyx(®) and SinaDoxosome(®). DOX induced-ECG changes were not detected in nano-formulations. No significant alteration was found in biochemical indexes of myocardial injury in mice exposed to nano-formulations in comparison with control mice. The tissue oxidative parameters such as lipid peroxidation, glutathione, catalase and superoxide dismutase was significantly changed as the results of free DOX treatment. However, the oxidative status of Caelyx(®) and SinaDoxosome(®) treated animals did not showed any changes. The experiment also revealed that apoptotic pathway was not activated in the heart of mice exposed to nano-formulations. CONCLUSIONS: Although this investigation showed that Caelyx(®) and SinaDoxosome(®) are similar in terms of biodistribution, efficacy and toxicity, appropriate clinical evaluations in patients should be considered.


Subject(s)
Colonic Neoplasms/drug therapy , Colonic Neoplasms/metabolism , Doxorubicin/analogs & derivatives , Xenograft Model Antitumor Assays , Animals , Antibiotics, Antineoplastic , Apoptosis/drug effects , Cell Line, Tumor , Doxorubicin/adverse effects , Doxorubicin/pharmacokinetics , Doxorubicin/therapeutic use , Humans , Liver/metabolism , Male , Mice , Myocardium/metabolism , Myocardium/pathology , Oxidative Stress/drug effects , Particle Size , Polyethylene Glycols/adverse effects , Polyethylene Glycols/pharmacokinetics , Polyethylene Glycols/therapeutic use , Tissue Distribution
5.
Drug Res (Stuttg) ; 65(7): 337-43, 2015 Jul.
Article in English | MEDLINE | ID: mdl-24696423

ABSTRACT

Crocus sativus L., commonly known as saffron, is a perennial stemless herb in Iridaceae family. It has been used in traditional medicine as well as in modern pharmacological studies for variety of conditions including depression. Recent studies have suggested brain-derived neurotrophic factor (BDNF), VGF Neuropeptide, Cyclic-AMP Response Element Binding Protein (CREB) and phospho-CREB (p-CREB) may play roles in depression. In this research the molecular mechanism of antidepressant effect of aqueous extract of saffron and its effect on the levels of BDNF, VGF, CREB and p-CREB in rat hippocampus, were investigated. The aqueous extract of saffron (40, 80 and 160 mg/kg/day) and imipramine 10 mg/kg/day were injected intraperitoneally (i.p.) for 21 days to rats. The FST (forced swimming test) was performed on the days 1(st) and 21(st). The protein expression and transcript levels of BDNF, VGF CREB and phospho-CREB in rat hippocampus, were evaluated using western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The results of FST showed that saffron reduced the immobility time. The protein levels of BDNF, CREB and p-CREB were significantly increased in saffron treated rats. VGF protein expression was also increased, but not significantly. The transcript levels of BDNF significantly increased. No significant changes in CREB and VGF transcript levels were observed. It was concluded that aqueous extract of saffron has antidepressant effects and the mechanism of its antidepressant effect may be due to increasing the levels of BDNF, VGF, CREB and P-CREB in rat hippocampus.


Subject(s)
Antidepressive Agents/pharmacology , Brain-Derived Neurotrophic Factor/biosynthesis , Crocus/chemistry , Cyclic AMP Response Element-Binding Protein/biosynthesis , Hippocampus/drug effects , Neuropeptides/biosynthesis , Plant Extracts/pharmacology , Animals , Brain-Derived Neurotrophic Factor/genetics , Cyclic AMP Response Element-Binding Protein/genetics , Dose-Response Relationship, Drug , Gene Expression/drug effects , Hippocampus/metabolism , Imipramine/pharmacology , Male , Neuropeptides/genetics , Phosphorylation/drug effects , RNA, Messenger/metabolism , Rats
6.
Drug Res (Stuttg) ; 65(11): 561-6, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25368905

ABSTRACT

INTRODUCTION: Organophosphate compounds, such as diazinon (DZN), are widely used in agriculture and can lead to formation of reactive oxygen species (ROS) in cardiovascular system. ROS are highly toxic since they can cause serious changes in proteins including ubiquitylation. Crocin (a carotenoid isolated from saffron), has protective effects against DZN cardiotoxicity. In this study level of total protein ubiquitylation as markers of oxidative stress and level of ubiquitin-HIF-1α and P53, known substrates of ubiquitylation, in rat hearts exposed to DZN and crocin were evaluated. METHODS: Rats were divided into 7 groups: corn oil (control), DZN (15 mg/kg/day, gavage), crocin (12.5, 25, 50 mg/kg/day, i. p.) plus DZN, vitamin E (200 IU/kg, i. p., 3 days a week) plus DZN and crocin (50 mg/kg/day, i. p.). Treatments were continued for 4 weeks. Total protein ubiquitylation, total HIF-1α and P53 were analyzed by western blotting. Total HIF-1α and P53 were purified by immunoprecipitation (IP) and ubiquitin- HIF-1α and P53 were analyzed by western blotting. RESULTS: Higher protein ubiquitylation levels were observed in DZN treated rats. Decrease in ubiquitin-HIF-1α was also shown, and leads to higher HIF-1α protein levels in DZN group. Crocin (50 mg/kg) and vit. E protected cells against DZN protein ubiquitylation. Significant differences were not observed between the ubiquitin - P53 and total P53 protein levels. CONCLUSION: Our results showed that ubiquitylation could be considered as a marker of oxidative stress in rats exposed to DZN. Increase in level of HIF-α may compensate adverse effect of DNZ in rat heart.


Subject(s)
Cardiotoxicity/prevention & control , Carotenoids/pharmacology , Diazinon/toxicity , Oxidative Stress/drug effects , Animals , Cardiotonic Agents/administration & dosage , Cardiotonic Agents/isolation & purification , Cardiotonic Agents/pharmacology , Carotenoids/administration & dosage , Carotenoids/isolation & purification , Crocus/chemistry , Dose-Response Relationship, Drug , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Insecticides/toxicity , Male , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Tumor Suppressor Protein p53/metabolism , Ubiquitination/drug effects , Vitamin E/pharmacology
7.
J Endocrinol Invest ; 37(11): 1031-40, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25125023

ABSTRACT

BACKGROUND: Metabolic syndrome is an important risk factor for cardiovascular disease (CVD) occurrence and mortality. CVDs are leading cause of death worldwide. Recently, there has been an increasing interest in the use of herbal medicines with more efficiency and minimal undesirable effects than chemical drugs for a variety of disorders including CVD. Nigella sativa and its active constituent, thymoquinone, have been documented to exhibit antidiabetic, antiobesity, hypotensive and hypolipidemic properties. AIM: In this review, we discussed the most relevant articles to find out the role of N. sativa in different components of metabolic syndrome and CVD risk factors including high blood pressure, obesity, dyslipidemia and high blood glucose. CONCLUSIONS: This review suggests a potential role of N. sativa and TQ in the management of metabolic syndrome, however more studies should be conducted to evaluate their effectiveness.


Subject(s)
Benzoquinones/therapeutic use , Metabolic Syndrome/drug therapy , Nigella sativa , Plant Extracts/therapeutic use , Animals , Benzoquinones/chemistry , Benzoquinones/isolation & purification , Cardiovascular Diseases/blood , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/epidemiology , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/isolation & purification , Hypoglycemic Agents/therapeutic use , Metabolic Syndrome/blood , Metabolic Syndrome/epidemiology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Treatment Outcome
8.
J Hosp Infect ; 83 Suppl 1: S29-34, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23453173

ABSTRACT

The human immune system is inseparably bonded to an individual's personal micro-biome from birth to death. Since the beginning of life, commensal relationships have ensured the survival of micro- and macro-organisms within complex relationships. However, technological advances and altered lifestyle imposed new rules for this interaction during recent decades. It has been observed that reduced exposure to micro-organisms and parasites results in decreased morbidity and mortality, but is also associated with a rising prevalence of atopic disorders and autoimmune diseases, mostly in industrialized countries. This inverse relationship is described by the 'hygiene hypothesis', put forward in 1989, yet this term only imperfectly describes these observations, as excessive hygiene or hygienic measures may not directly be the central cause. The lack of appropriate immune stimulation during early childhood with the consequence of disturbed alignment in the sequence of encountering self- or non-self-antigens might account in the rise of atopy and autoimmune disease. For this reason we propose the term 'early immune challenge hypothesis'. This concept highlights the importance of immune priming in early life in the context of genetic, social, geographic, cultural, and economic background. Moreover, it emphasizes the central role of 'training' of regulatory T-cells through sufficient microbial exposure, leading to a robust, healthy balance between inflammation and anti-inflammation or immune tolerance. Insufficient exposure might result in abnormal immune regulatory development. Finally, it incorporates the idea of encountering 'old friends' - organisms that shaped our immune system during human phylogeny. This article gives a comprehensive overview of the relationship between microbial exposure, and the incidence of asthma and hay fever is outlined. Although the outcomes of these studies originally were interpreted in the framework of the hygiene hypothesis, they may suit the concept of the hypothesis of early immune challenge even better. Moreover, recent studies have revealed that TH or TReg imbalances in disease may be partially corrected by the administration of helminthic or bacterial extracts.


Subject(s)
Autoimmune Diseases/epidemiology , Hygiene Hypothesis , Hypersensitivity/epidemiology , Autoimmune Diseases/etiology , Autoimmune Diseases/prevention & control , Health , Humans , Hypersensitivity/etiology , Hypersensitivity/prevention & control , Incidence
9.
J Obstet Gynaecol ; 30(1): 30-4, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20121500

ABSTRACT

The aim was to determine if selenium supplementation during pregnancy reduces the occurrence of premature (pre-labour) rupture of membranes (PROM). A total of 166 primigravid pregnant women in the first trimester of pregnancy, were randomised to receive 100 microg of selenium (n = 83, drop-outs = 22) or a placebo (n = 83, drop-outs = 19) per day until delivery. The incidence of PROM, as well as serum selenium concentrations were evaluated at baseline and at the end of the study. Supplementation with selenium was associated with a significant increase in mean serum selenium concentration at term (p < 0.001). In contrast, mean serum selenium concentration remained unchanged in the control group (p > 0.05). The incidence of PROM was significantly lower in the selenium group (n = 8, 13.1%) than in the control group (n = 22, 34.4%) (p < 0.01). Our findings indicate that selenium supplementation (100 microg/day) in pregnant women effectively reduces the incidence of PROM.


Subject(s)
Antioxidants/therapeutic use , Fetal Membranes, Premature Rupture/prevention & control , Selenium/therapeutic use , Adult , Dietary Supplements , Double-Blind Method , Female , Humans , Pregnancy , Selenium/blood , Young Adult
10.
Infection ; 35(5): 300-7, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17885732

ABSTRACT

Clostridium difficile is a well-known cause of sporadic and healthcare-associated diarrhea. Multihospital outbreaks due to a single strain and outbreaks associated with antibiotic selective pressure, especially clindamycin, have been well documented. Severe cases and fatalities from C. difficile are uncommon. The recent global emergence of a hypervirulent strain containing binary toxin (Toxinotype III ribotype 027), with or without deletion in a regulatory gene (tcdC gene), together with high-level resistance to third generation fluoroquinolones, has been associated with increased morbidity and mortality. Although the defective regulatory gene locus is associated with increased toxin production in vitro, the in vivo significance of this mutation and of the binary toxin remains undefined. To date, treatment strategies have not evolved in response to the emergence of this hypervirulaent strain. We provide a critical, quantitative summary of the evolving clinical and molecular epidemiology of C. difficile along with implications relevant to future treatment strategies.


Subject(s)
Anti-Bacterial Agents/pharmacology , Clostridioides difficile/drug effects , Clostridioides difficile/pathogenicity , Diarrhea/microbiology , Drug Resistance, Bacterial , Fluoroquinolones/pharmacology , Adult , Aged, 80 and over , Bacterial Proteins/biosynthesis , Bacterial Proteins/genetics , Community-Acquired Infections/epidemiology , Community-Acquired Infections/microbiology , Community-Acquired Infections/mortality , Cross Infection/epidemiology , Cross Infection/microbiology , Cross Infection/mortality , Diarrhea/epidemiology , Diarrhea/mortality , Humans , Molecular Epidemiology , Promoter Regions, Genetic , Repressor Proteins/biosynthesis , Repressor Proteins/genetics , Virulence
11.
Infection ; 30(1): 38-40, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11876515

ABSTRACT

Disseminated nocardiosis has never been described before in a patient with Waldenstrom macroglobulinemia. We report an unusual case of disseminated nocardiosis in a patient with Waldenstrom macroglobulinemia who presented with pulmonary non-caseating granulomas. The patient was successfully treated with trimethoprim-sulfamethoxazole (TMP-SMX) for 1 year.


Subject(s)
Nocardia Infections/complications , Nocardia asteroides , Plasma Cell Granuloma, Pulmonary/microbiology , Waldenstrom Macroglobulinemia/complications , Abscess , Discitis/microbiology , Humans , Lumbar Vertebrae , Male , Middle Aged , Nocardia Infections/diagnostic imaging , Osteomyelitis/microbiology , Plasma Cell Granuloma, Pulmonary/diagnostic imaging , Psoas Abscess/microbiology , Radiography
12.
Infection ; 30(1): 41-2, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11876516

ABSTRACT

Pneumocystis carinii is a common cause of pneumonia in patients with AIDS, however, the incidence has dropped with the availability of effective prophylactic regimens. First-line treatment for both acute Pneumocystis pneumonia and chronic prophylaxis is trimethoprim/sulfamethoxazole (TMP/SMX). This combination can cause hypersensitivity reactions as well as myelosuppression. The simultaneous administration of leucovorin during acute treatment has been shown to reduce the incidence of neutropenia, but may interfere with the efficacy of TMP/SMX. We report a case of P. carinii pneumonia in a patient with AIDS who failed TMP/SMX prophylaxis while taking leucovorin.


Subject(s)
AIDS-Related Opportunistic Infections/prevention & control , Anti-Infective Agents/therapeutic use , Leucovorin/administration & dosage , Pneumonia, Pneumocystis/prevention & control , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Adult , Drug Therapy, Combination , Humans , Male , Pneumocystis , Treatment Failure , Trimethoprim, Sulfamethoxazole Drug Combination/administration & dosage
13.
Infection ; 29(6): 357-8, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11787842

ABSTRACT

Herpes simplex virus (HSV) is a common cause of viral encephalitis. Herpes simplex encephalitis (HSE) typically presents with acute neurologic changes and the initial cerebrospinal fluid examination is nearly always abnormal. We report a case of a patient with HSE and normal initial CSF analysis. This resulted in delayed diagnosis and therapy with subsequent severe neurolgical sequelae. Herpes simplex infection should be included in the differential diagnosis of encephalopathic patients and a normal CSF examination.


Subject(s)
Encephalitis, Herpes Simplex/cerebrospinal fluid , Encephalitis, Herpes Simplex/diagnosis , Simplexvirus/isolation & purification , Anti-Bacterial Agents , DNA, Viral/isolation & purification , Diagnosis, Differential , Drug Therapy, Combination/therapeutic use , Encephalitis, Herpes Simplex/drug therapy , Humans , Male , Middle Aged , Polymerase Chain Reaction , Severity of Illness Index , Simplexvirus/genetics , Time Factors , Treatment Outcome
14.
Diagn Microbiol Infect Dis ; 38(3): 173-5, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11109017

ABSTRACT

A patient presented with chronic leg ulcers after a mowing accident. He received several courses of antibiotics for presumed cellulitis, underwent surgical debridement, and was treated empirically with cyclosporin for presumed pyoderma gangrenosum, all without improvement. Cultures from prior debridement revealed Mycobacterium kansasii, and he was successfully treated with triple antituberculous regimen. Cutaneous infections due to this slow growing Mycobacterium are rare and may resemble cellulitis or sporotrichosis. Mycobacterium kansasii should be included in the differential diagnosis of skin infections with an indolent course and lack of response to antibiotics.


Subject(s)
Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium kansasii/isolation & purification , Skin Diseases, Bacterial/diagnosis , Skin Diseases, Bacterial/microbiology , Adult , Diagnosis, Differential , Humans , Immunocompetence , Male , Mycobacterium kansasii/classification , Mycobacterium kansasii/genetics
15.
Arch Neurol ; 57(9): 1363-5, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10987906

ABSTRACT

BACKGROUND: It is known that exertion can aggravate migraine headache. However, the relationship between exertion and migraine aura is unknown. OBJECTIVE: To study the relationship between exertion and migraine aura. DESIGN: Case report. SETTING: Tertiary care hospital. PATIENT: A 67-year-old man presented with recurrent attacks of exertion-induced hemiplegic migraine. Since the hemiparetic attacks were exertion induced, they were initially ascribed to recurrent transient ischemic attacks. However, the clinical picture, normal findings on cerebral angiography and neuroimaging (during the period of hemiparesis), lack of response to treatment with antiplatelets and anticoagulants, and successful treatment with verapamil suggested that the hemiparesis was not due to ischemia, but was indeed a migraine aura. We suggest that exertion induced the aura of hemiparesis by lowering the threshold for the development of cortical spreading depression. Even though our patient had no family history of hemiplegic migraine, a mutation in an ion channel gene (eg, the CACNA1A gene on chromosome 19) might account for his episodic attacks. CONCLUSION: Migraine aura should be included in the differential diagnosis of exertion-induced focal neurologic deficit.


Subject(s)
Hemiplegia/etiology , Migraine Disorders/etiology , Physical Exertion , Aged , Brain Ischemia/diagnosis , Calcium Channel Blockers/therapeutic use , Diagnosis, Differential , Exercise , Hemiplegia/diagnosis , Humans , Male , Migraine Disorders/diagnosis , Migraine Disorders/drug therapy , Severity of Illness Index , Verapamil/therapeutic use
19.
Diagn Microbiol Infect Dis ; 37(1): 75-6, 2000 May.
Article in English | MEDLINE | ID: mdl-10794944

ABSTRACT

A diabetic patient was admitted with ear pain and purulent discharge after "high ear piercing" by a friend. After investigation she was found to have chondritis, complicated by an abscess. Wound cultures grew Lactobacillus species. Patient responded to parenteral antibiotics without suffering cosmetic deformity. Sterile technique, adherence to post-piercing ear hygiene, and avoiding piercing the auricular cartilage may prevent complications associated with ear piercing. Lactobacillus should be included in the differential of pathogens involved in post-piercing chondritis.


Subject(s)
Cartilage Diseases/microbiology , Ear Cartilage/injuries , Gram-Positive Bacterial Infections/microbiology , Lactobacillus , Wound Infection/microbiology , Adolescent , Cartilage Diseases/drug therapy , Cartilage Diseases/physiopathology , Clavulanic Acids/therapeutic use , Drug Therapy, Combination/therapeutic use , Female , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/physiopathology , Humans , Lactobacillus/isolation & purification , Ticarcillin/therapeutic use , Treatment Outcome , Wound Infection/drug therapy , Wound Infection/physiopathology
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