Investigating effects of hydroalcoholic extract of saffron on sex hormones in female rats undergoing chemotherapy with cyclophosphamide

Cyclophosphamide is an antineoplastic medicine that causes disorder in functions of the body systems. Thus, the purpose of this study is to investigate the effect of hydroalcoholic extract of saffron on improving the complications of cyclophosphamide on sex hormones. Fifty-six adult female Wistar rats were randomly divided into seven groups; control, sham (received distilled water, solvent extract, and drug), experimental groups 1, 2, and 3 (received cyclophosphamide (5 mg/kg/bw) + hydroalcoholic extract of saffron (2, 1, and 0.5 g/kg/bw), experimental group 4 (saffron 2 g/kg/bw), and experimental group 5 (cyclophosphamide 5 mg/kg/bw). Cyclophosphamide was given intraperitoneally, and extract by gavage was prescribed for 21 days. At the end of the experiment, after blood and preparation of serum, ELISA method was used for measuring the estrogen, progesterone, FSH, and LH hormones. Data and LSD test were analyzed with SPSS software (version 18). Results show that the concurrent use of low-dose cyclophosphamide and saffron extract can reduce toxic effect of cyclophosphamide on pituitary-gonadal axis and cause estrogen to be produced.     

T helper 17 cells play a critical pathogenic role in lung cancer

Lung cancer development is associated with extensive pulmonary inflammation. In addition, the linkage between chronic obstructive pulmonary disease (COPD) and lung cancer has been demonstrated in population-based studies. IL-17–producing CD4 helper T cells (Th17 cells) play a critical role in promoting chronic tissue inflammation. Although Th17 cells are found in human COPD and lung cancer, their role is not understood. We have thus used a mouse model of lung cancer, in which an oncogenic form of K-ras (K-ras^G12D), frequently found in human lung cancer, is restrictedly expressed in lung epithelial cells [via Clara cell secretory protein (CCSP^cre)]. In this model, Th17 and Treg but not Th1 cells were found enriched at the tumor tissues. When CCSP^cre/K-ras^G12D mice were weekly challenged with a lysate of nontypeable Haemophilus influenza (NTHi), which induces COPD-type inflammation and accelerates the tumor growth, they showed greatly enhanced Th17 cell infiltration in the lung tissues. Lack of IL-17, but not IL-17F, resulted in a significant reduction in lung tumor numbers in CCSP^cre/K-ras^G12D mice and also those treated with NTHi. Absence of IL-17 not only resulted in reduction of tumor cell proliferation and angiogenesis, but also decreased the expression of proinflammatory mediators and reduced recruitment of myeloid cells. Depletion of Gr-1⁺CD11b⁺ myeloid cells in CCSP^cre/K-ras^G12D mice suppressed tumor growth in lung, indicating Gr-1⁺CD11b⁺ myeloid cells recruited by IL-17 play a protumor role. Taken together, our data demonstrate a critical role for Th17 cell-mediated inflammation in lung tumorigenesis and suggest a novel way for prevention and treatment of this disease.Inflammation plays an important role in tumor development (1, 2). Although targeting inflammation and tumor microenvironment has been considered as a new direction of cancer therapy, the mechanisms underlying cancer-associated inflammation have not been well understood. Lung cancer is a leading cause of death in the world. Accumulating evidence has shown that inflammation is associated with pathogenesis of lung cancer, especially those induced by cigarette smoke (3). The primary risk factor among smokers to develop lung cancer is the presence of chronic obstructive pulmonary disease (COPD) (4), which is characterized by chronic pulmonary inflammation, airway remodeling and destruction of lung parenchyma. Human lung cancers are inflicted with alterations in various subsets of lymphocytes and myeloid cells (5, 6), reminiscent of immune activation during chronic inflammation. Several studies have shown NFκB signaling as a mechanistic link between inflammation and lung cancer using a mouse model of lung adenocarcinoma (7, 8). However, the specific inflammatory cell types or molecules potentiating lung cancer are not understood clearly.We and others have identified a novel subset of CD4 helper T cells that produce IL-17 and are referred as Th17 cells (9, 10). Th17 cells have been associated with inflammatory diseases such as rheumatoid arthritis, asthma, lupus, and allograft rejection. An important function of IL-17 is to promote tissue inflammation through the up-regulation of proinflammatory cytokines and chemokines (11). Consistently, we have shown that transgenic overexpression of IL-17 in the lungs resulted in chemokine up-regulation and tissue infiltration by leukocytes, although mice treated with neutralizing IL-17–specific antibody were also found to be resistant to the induction of experimental autoimmune encephalomyelitis (9). These and other studies collectively demonstrated that IL-17 and Th17 cells play nonredundant function in promoting inflammation.Increased frequencies of IL-17 and Th17 cells have been reported in patients with different types of tumors (12), including lung adenocarcinoma (13). The density of intratumoral IL-17–positive cells in primary human nonsmall cell lung cancer was inversely correlated with patient outcome and correlated with smoking status of the patients (14). Th17 cells specific for a common tumor antigen were found in lung cancer patients as part of their spontaneous immune response to the autologous tumor (15). However, the function of Th17 cells and IL-17 in the development of lung cancer remains to be shown. Animal model studies have revealed contrasting roles of IL-17 in various tumors (16). Tumor-promoting effect of IL-17 was shown in some models such as colon cancer (17–20), whereas in others, IL-17 supported anti-tumor immunity, including in B16 melanoma model (21–24). Thus, the role of IL-17 could be complex and tumor-specific.To properly evaluate the role of IL-17 in inflammation-associated lung cancer, we used a model of oncogenic K-ras mutation expressed only in the lung. Mice expressing K-ras mutation in Clara cells (CCSP^cre/K-ras^G12D mice) spontaneously develop lung adenocarcinoma (25). In addition, we induced COPD-type lung inflammation by challenging mice with lysates of nontypeable Haemophilus influenza (NTHi). Inflammation driven by NTHi can promote tumor growth in CCSP^cre/K-ras^G12D mice (25). These experiments collectively indicate a tumorigenic role of IL-17–mediated inflammation in the development of lung cancer.     

Randomized controlled trial of aripiprazole versus risperidone for the treatment of amphetamine-induced psychosis

Background: Lifetime prevalence of amphetamine-induced psychotic disorder is reported as being up to 23% for methamphetamine (MA) abusers. Approximately 25% of those with a baseline DSM-IV diagnosis of substance-induced psychosis are diagnosed with primary psychosis at one-year follow-up. Evidence on the treatment of amphetamine psychosis is very limited. Objectives: To investigate the efficacy of risperidone versus aripiprazole in treatment of amphetamine-induced psychotic symptoms. Methods: In a double-blind study, 45 participants were randomly allocated to either aripiprazole 15?mg or risperidone 4?mg daily over a six-week trial. Positive and negative symptoms of psychosis were assessed using the Scale for Assessment of Negative Symptoms (SANS) and the Scale for Assessment of Positive Symptoms (SAPS) at baseline and completion of the trial. Results: SANS and SAPS scores decreased significantly in both groups. Mean SAPS score reduction in risperidone and aripiprazole group was 16.20 and 10.80, respectively, after trial course (p?p?=?0.08). Conclusions: Both aripiprazole and risperidone were effective for patients diagnosed with amphetamine-induced psychotic disorder. However, risperidone had the greater effect on positive psychotic symptoms while patients with negative symptoms may respond better to aripiprazole. There is a case for further studies evaluating the efficacy of atypical antipsychotics in this disorder.