Recent findings on the role of fungal products in the treatment of cancer.

In modern medicine, natural products have aided humans against their battles with cancer. Among these products, microorganisms, medicinal herbs and marine organisms are considered to be of great benefit. In recent decades, more than 30 fungal immunity proteins have been identified and proved to be extractable from a wide range of fungi, including mushrooms. Although chemotherapy is used to overcome cancer cells, the side effects of this method are of great concern in clinical practice. Fungal products and their derivatives constitute more than 50% of the clinical drugs currently being used globally. Approximately 60% of the clinically approved drugs for cancer treatment have natural roots. Anti-tumor immunotherapy is prospective with a rapidly growing market worldwide due to its high efficiency, immunity, and profit. Polysaccharide extracts from natural sources are being used in clinical and therapeutic trials on cancer patients. This review aims to present the latest findings in cancer treatment through isolated and extraction of fungal derivatives and other natural biomaterials.

Inhibition of corticosterone synthesis and its effect on acute phase proteins, heat shock protein 70, and interleukin-6 in broiler chickens subjected to feed restriction.

The aim of the current study was to elucidate whether inhibition of corticosterone (CORT) synthesis could modify stress response to feed deprivation and its possible interactions with feed restriction in the neonatal period in broiler chickens. Equal numbers of broiler chicks were subjected to either 60% feed restriction (60FR) or ad libitum (AL) on d 4, 5, and 6. On day 7, blood CORT, acute phase proteins (APP), interleukin-6 (IL-6) levels, and brain heat shock protein 70 (HSP70) expression were determined. On d 35, chickens in each early age feeding regimen were subjected to one of the following treatments: (i) ad libitum feeding (ALF), (ii) 24 h feed deprivation (SFR), or (iii) 24 h feed deprivation with intramuscular injection of 1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane (DDT) at 100 mg/kg BW (SFR+DDT). The effect of SFR on CORT, APP, IL-6, and HSP 70 were determined on d 36. The results showed that subjecting chicks to 60FR significantly elevated CORT and brain HSP70 concentration compared to the AL group on d 7. The early feeding regimen had no significant effect on CORT, alpha-1 acid glycoprotein (AGP), ovotransferrin (OVT), ceruoplasmin (CP), IL-6, or brain HSP70 on d 36. The CORT, AGP, OVT, CP, IL-6, and brain HSP70 expression of SFR birds following 24 h of feed deprivation (d 36) were significantly higher than their ALF and SFR+DDT counterparts. Both ALF and SFR+DDT birds had similar values. Stress attributed to feed deprivation without concurrent increase in CORT had a negligible effect on serum levels of APP and IL-6 and brain HSP70 expression.

The Incidence of Cytomegalovirus Glycoprotein B Genotypes in Kidney Transplant Recipients in Iran.

BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic viral infection in kidney transplant recipients. CMV classification is usually based on its glycoprotein B (gB) genotypes, which divides the virus into 4 strains (gB1-4). OBJECTIVE: To determine the incidence of CMV genotypes in Iran and their relation to various clinical factors. METHODS: We studied 80 renal transplant recipients admitted to our transplant referral center between 2014 and 2015. All of the studied patients were monitored every 1-2 weeks for CMV infection by immunofluorescence method. There were 34 CMV-infected patients whose sera were studied with sequencing technique to identify the 4 CMV genotypes. All patients were followed up to 6 months after transplantation. RESULTS: gB1 was the most common genotype (35.3%); it was followed by gB3 and gB4 (each with 17.6 %), gB2, and mixed gB1,3 and gB1,2 (each with 14.7%). Age (p=0.037), time of infection after transplantation (p=0.011), and biopsy-proven rejection (p=0.012) were associated with CMV genotype. After adjusting for covariates, significant associations were found between genotype gB1 and family relationship (p=0.047) as well as HLA mismatch (p=0.014); genotype gB3 and family relationship (p=0.011); and genotype gB4 and age (p=0.019). CONCLUSION: The most common CMV gB genotype in CMV-infected kidney transplant recipients in Iran was gB1. We recommend considering related therapeutic applications in the management of such patients.

Epidemiological and mycological characteristics of candidemia in Iran: A systematic review and meta-analysis.

To date, there has been no comprehensive review of the epidemiology, risk factors, species distribution, and outcomes of candidemia in Iran. This study aimed to perform a systematic review and meta-analysis of all reported candidemia cases in Iran until December 2015. The review process occurred in three steps, namely a literature search, data extraction and statistical analyses. After a comprehensive literature search, we identified 55 cases. The mean age of patients was 46.80±24.30 years (range 1-81 years). The main risk factors for candidemia were surgery and burns (23.6%), followed by malignancies (20%), use of broad-spectrum antibiotics (18.2%), and diabetes (7.3%). Candida parapsilosis (n=17, 30.8%) was the leading agent, followed by Candida albicans (n=15, 27.3%), Candida glabrata (n=10, 18.2%), and Candida tropicalis (n=8, 14.5%). The frequencies of candidemia cases due to C. glabrata, C. parapsilosis, and C. albicans were significantly higher among patients aged>60, 21-40, and 41-60 years, respectively. Comparison of risk factors for candidemia by multiple logistic regression showed that one of the most important risk factors was surgery (OR: 4.245; 95% CI: 1.141-15.789; P=0.031). The outcome was recorded in only 19 cases and 13 of those patients (68.4%) expired. This study confirms that knowledge of the local epidemiology is important when conducting surveillance studies to prevent and control candidemia and will be of interest for antifungal stewardship.

Successful treatment with caspofungin of candiduria in a child with Wilms tumor; review of literature.

Symptomatic candiduria often occurs in patients with indwelling bladder catheters or immunocompromised host. Isolation of Candida in urine in high-risk patients should primarily be considered as a marker for candidemia. Hematological and genitourinary malignancies are one of the main risk factors associated with Candida urinary tract infections (CUTI). Fluconazole is a choice for initial treatment of CUTI, but it is fluctuate depending on the patient's condition including renal failure, site of urinary infection and Candida species. Poor glomerular filtration is the main disadvantage echinocandins resulting in very low urinary concentrations. Therefore, echinocandins have prohibited their use in CUTI. Up to now, there are only 10 cases reported in the literatures with highly effective echinocandins in CUTI because of high concentrations in the tissue are needed to control invasive fungal disease. Herein, we report a candiduria followed by renal candidiasis caused by Candida albicans in a 6-year-old Iranian male with a history of Wilms tumor in left kidney. Direct examination of urine specimen revealed an infection due to budding yeast cells with numerous pseudohyphae and growths of C. albicans was reconfirmed by sequencing of ITS rDNA region. MICs in increasing order were as follows: caspofungin (0.016µg/ml), voriconazole (0.125µg/ml), amphotericin B (0.25µg/ml), itraconazole (0.5µg/ml) and fluconazole (2µg/ml). It seems that successful treatment with caspofungin owes achieved high renal tissue concentrations that are unrelated to glomerular filtration. In conclusion, predisposing factors for better outcome are more important than treatment of CUTI, therefore, management of UTI is essential for critically patients.

Effects of Laser Physical Parameters on Lesion Size in Retinal Photocoagulation Surgery: Clinical OCT and Experimental Study.

INTRODUCTION: The aim of the present study was to determine burn intensity in retinal laser photocoagulation based on laser parameters; wavelength, power, beam size and pulse duration, using Optical Coherence Tomography (OCT), fundus camera, physical eye model and computer simulation in a clinical study. MATERIALS AND METHODS: Participants were 10 adult patients between 50-80 years with proliferative diabetic retinopathy. A multicolor-photo coagulator with 532 nm green and 672 nm red for retina photocoagulation in diabetic retinopathy was used to investigate the participants. Lesion size was measured for spot sizes 50 and 100 µm, with 100 and 150 mW laser power, and pulse duration 50 and 100 ms by OCT. Artificial eye and Zemax-optical design software were used with the same laser parameters. RESULTS: Appearance of OCT and fundus images showed direct relationship between retina burn size and lesion intensity with exposure time and power and also reverse relationship with laser spot size. Compared to red wavelength, burn size and lesion intensity increased in green wavelength. On the other hand, results from physical eye model were the same as clinical examination shown. Laser spot size in retina with Zemax simulation demonstrated that red wavelength was greater than green one. CONCLUSION: This study showed shorter pulses provide decrease in duration of laser surgery with significantly reduced pain. Results and calculations described in this article can help clinicians adjusting the required total coagulated area, the number of lesions and pattern density.

Survey of the Effects of Exposure to 900 MHz Radiofrequency Radiation Emitted by a GSM Mobile Phone on the Pattern of Muscle Contractions in an Animal Model.

BACKGROUND: The rapid development of wireless telecommunication technologies over the past decades, has led to significant changes in the exposure of the general public to electromagnetic fields. Nowadays, people are continuously exposed to different sources of electromagnetic fields such as mobile phones, mobile base stations, cordless phones, Wi-Fi routers, and power lines. Therefore, the last decade witnessed a rapidly growing concern about the possible health effects of exposure to electromagnetic fields emitted by these sources. MATERIALS AND METHODS: In this study that was aimed at investigating the effects of exposure to radiofrequency (RF) radiation emitted by a GSM mobile phone on the pattern of contraction in frog's isolated gastrocnemius muscle after stimulation with single square pulses of 1V (1 Hz), pulse height of contractions, the time interval between two subsequent contractions and the latency period were measured. RESULTS: Our findings showed that the pulse height of contractions muscle could be affected by the exposure to electromagnetic fields. Especially, the latency period was effectively altered in RF-exposed samples. However, none of the experiments could show an alteration in the time interval between two subsequent contractions after exposure to electromagnetic fields. CONCLUSION: These findings support early reports which indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians including the effects on the pattern of muscle extractions.

Exposure to Radiofrequency Radiation Emitted from Common Mobile Phone Jammers Alters the Pattern of Muscle Contractions: an Animal Model Study.

INTRODUCTION: The rapid growth of wireless communication technologies has caused public concerns regarding the biological effects of electromagnetic radiations on human health. Some early reports indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians such as the alterations of the pattern of muscle extractions. This study is aimed at investigating the effects of exposure to radiofrequency (RF) radiation emitted from mobile phone jammers on the pulse height of contractions, the time interval between two subsequent contractions and the latency period of frog's isolated gastrocnemius muscle after stimulation with single square pulses of 1V (1 Hz). MATERIALS AND METHODS: Frogs were kept in plastic containers in a room. Animals in the jammer group were exposed to radiofrequency (RF) radiation emitted from a common Jammer at a distance of 1m from the jammer's antenna for 2 hours while the control frogs were only sham exposed. Then animals were sacrificed and isolated gastrocnemius muscles were exposed to on/off jammer radiation for 3 subsequent 10 minute intervals. Isolated gastrocnemius muscles were attached to the force transducer with a string. Using a PowerLab device (26-T), the pattern of muscular contractions was monitored after applying single square pulses of 1V (1 Hz) as stimuli. RESULTS: The findings of this study showed that the pulse height of muscle contractions could not be affected by the exposure to electromagnetic fields. However, the latency period was effectively altered in RF-exposed samples. However, none of the experiments could show an alteration in the time interval between two subsequent contractions after exposure to electromagnetic fields. CONCLUSION: These findings support early reports which indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians including the effects on the pattern of muscle extractions.

Acute phase proteins, interleukin 6, and heat shock protein 70 in broiler chickens administered with corticosterone.

An experiment was conducted to determine the effect of corticosterone (CORT) administration on serum ovotransferrin (OVT), α1-acid glycoprotein (AGP), ceruloplasmin (CPN), and IL-6 concentrations, and brain heat shock protein (HSP) 70 expression in broiler chickens. From 14 to 20 d of age, equal numbers of birds were subjected to either (i) daily intramuscular injection with CORT in ethanol:saline (1:1, vol/vol) at 6 mg/kg of BW, or (ii) daily intramuscular injection with 0.5 mL ethanol:saline (1:1, vol/vol; control). Blood samples were collected before CORT treatment (14 d old), 3 and 7 d after CORT injections, and 4 d after cessation of CORT administration for determination of serum levels of CORT, OVT, AGP, CPN, and IL-6. Brain samples (whole cerebrum) were collected to measure HSP 70 density. Although CORT administration significantly increased feed intake, weight gain was significantly depressed. Administration of CORT also increased CORT, OVT, CPN, AGP, IL-6, and HSP 70 expression. Four days following cessation of CORT administration, OVT declined to the basal level but not CPN and AGP. In conclusion, an elevation in CORT can induce an acute-phase response and HSP 70 expression. Thus, APP and HSP 70 may be of value as indicators of stress in poultry.

Loss of sarcolemmal nNOS is common in acquired and inherited neuromuscular disorders.

OBJECTIVE: Neuronal nitric oxide synthase (nNOS), normally expressed at the sarcolemmal membrane, is known to be mislocalized to the sarcoplasm in several forms of muscular dystrophy. Our objectives were to characterize further the range of patients manifesting aberrant nNOS sarcolemmal immunolocalization and to study nNOS localization in animal models of nondystrophic myopathy. METHODS: We carried out a retrospective cross-sectional study. We performed immunofluorescent staining for nNOS on biopsy specimens from 161 patients with acquired and nondystrophin inherited neuromuscular conditions. The localization of sarcolemmal nNOS correlated with mobility and functional status. Muscle specimens from mouse models of steroid-induced and starvation-related atrophy were studied for qualitative and quantitative nNOS expression. RESULTS: Sarcolemmal nNOS staining was abnormal in 42% of patients with inherited myopathic conditions, 25% with acquired myopathic conditions, 57% with neurogenic conditions, and 93% with hypotonia. Interestingly, we found significant associations between mobility status or muscle function and sarcolemmal nNOS expression. Furthermore, mouse models of catabolic stress also demonstrated mislocalization of sarcolemmal nNOS. CONCLUSION: Our analyses indicate that nNOS mislocalization is observed in a broad range of nondystrophic neuromuscular conditions associated with impaired mobility status and catabolic stress. Our findings suggest that the assessment of sarcolemmal localization of nNOS represents an important tool for the evaluation of muscle biopsies of patients with a variety of inherited and acquired forms of neuromuscular disorders.

Immune responses in patients with metastatic renal cell carcinoma treated with dendritic cells pulsed with tumor lysate.

Patients with metastatic renal cell carcinoma (mRCC) have a limited life expectancy but still a subset of these patients develop immune and clinical responses after immunotherapy including dendritic cell (DC) vaccination. In a recently published phase I/II trials, fourteen HLA-A2 negative patients with progressive mRCC were vaccinated with autologous DC pulsed with allogeneic tumour lysate. Low-dose IL-2 administered subcutaneously was given concomitantly. In this study, we analysed lysate specific proliferation of PBMCs from these patients together with the TH1/TH2 balance of the responding T cells. Also, serum concentrations of IL-10, IL-12, IL-15, IL-17 and IL-18 from these patients and additional thirteen HLA-A2 positive mRCC patients treated with autologous DC pulsed with survivin and telomerase peptides were analysed during vaccination to identify systemic immune responses and potential response biomarkers. In HLA-A2 negative mRCC patients a spontaneous predominance of TH1 secreting tumour lysate specific T cells was observed prior to vaccination in patients attaining stable disease (SD) during treatment whereas patients with continued progressive disease (PD) had a mixed TH1/TH2 response. The TH1/TH2 balance was unchanged during vaccination also when tumour lysate specific T cell responses increased. An increase in IL-12, IL-17 and IL-18 serum concentrations was observed during vaccination but no difference between patients with SD and PD was observed. IL-10 or IL-15 was not measurable in serum.

Prevalence of left main coronary artery disease among patients with ischemic heart disease: insights from the Tehran Angiography Registry.

AIM: This study was designed to investigate the prevalence of left main coronary artery (LMCA) significant stenosis among patients with stable angina (SA) or acute coronary syndromes (ACSs) and to assess the influence of demographic and clinical profiles on these findings. METHODS: A review of the Angiography Registry demonstrated that 18137 patients had SA or ACSs. The patients' characteristics were compared in subgroups with and without LMCA disease. RESULTS: Significant and minimal LMCA stenoses were found in 659 (3.6%) and 1157 (6.4%) patients, respectively. An unprotected LMCA disease was estimated in 609 (3.4%) subjects. A cumulative Logit Model analysis revealed the male gender (odds ratio [OR]=1.480, 95% confidence interval [CI]=1.287 to 1.703; P<0.001), diabetes mellitus (OR=1.158, 95% CI=1.029 to 1.303; P=0.015), dyslipidemia (OR=1.125, 95% CI=1.001 to 1.265; P=0.048), and aging (OR=1.028, 95% CI=1.022 to 1.034; P<0.001) as the independent predictors of LMCA stenosis with coexistent diseases in the rest of the coronary arteries. In the patients with normal or minimal stenoses of the other coronary arteries, cigarette smoking (OR=3.749, 95% CI=1.698 to 8.070) was found to be the independent risk factor of isolated LMCA disease. Luminal stenosis >50% in the right coronary artery, the left circumflex artery, and the left anterior descending artery was significantly more frequent in association with LMCA disease. CONCLUSIONS: The patients with LMCA disease were more likely to be male, older, and have diabetes mellitus or dyslipidemia, whereas cigarette smoking was found as an independent predictor of isolated LMCA. There was a strong correlation between the severity of LMCA stenosis and coexistent diseases in the rest of the coronary arteries.

Peptic ulcer disease, irritable bowel syndrome and constipation in two populations in Iran.

OBJECTIVE: To determine the prevalence of peptic ulcer disease, irritable bowel syndrome (IBS) and chronic constipation in two Iranian populations (pastoral nomads and industrial labourers) with different life styles, and to evaluate the risk factors associated with these diseases. SUBJECTS: A total of 455 randomly selected pastoral nomads and 492 industrial labourers (all male) aged between 35-55 years. METHODS: Demographic and social data were obtained by interviews. An upper gastrointestinal tract endoscopy was performed and biopsy specimens were taken from subjects complaining of abdominal symptoms and randomly selected asymptomatic subjects. A urease test was performed on antral specimens. Serum pepsinogen I concentrations and Helicobacter pylori antibody titres were measured by radioimmunoassay and immunoglobulin (Ig) G enzyme-linked immunosorbent assay tests, respectively. RESULTS: Serum pepsinogen I concentrations were similar in both nomads and industrial labourers, and the percentage with positive antibody titres for H. pylori was high in both populations (86.3 and 91% in nomads and industrial labourers, respectively). Industrial labourers were twice as likely to have duodenal ulcer (P < 0.05) than nomads. The prevalence of duodenal ulcer disease and gastric ulcer was 4.6 and 0.6% in nomads and 10.3 and 0.4% in industrial labourers, respectively. The prevalence of IBS was similar in nomads (3.1%) and industrial labourers (3.6%). Fewer nomads (1.4%) than industrial labourers (3.3%) had chronic constipation. Logistic regression analysis showed that being an industrial labourer, or smoker and having undergone previous non-gastric surgery were risk factors for duodenal ulcer disease. When the variable 'urease test' was included in the logistic regression analysis, smoking, a positive urease test and the quantity of fruit eaten per week were associated risk factors. The risk factors associated with IBS were the use of analgesics and back pain. The only risk factor associated with chronic constipation was being an industrial labourer. CONCLUSIONS: Industrial labourers were twice as likely to have duodenal ulcer disease as nomads. The prevalence of IBS and chronic constipation in the two male Iranian populations was lower than that found in western countries. Duodenal ulcer disease was associated with H. pylori colonization but not with a positive serum antibody titre for H. pylori. H. pylori colonization of the antral mucosa and smoking are causative factors for duodenal ulcer disease and fruit intake is possibly an associated factor.