Cardiospermum halicacabum inhibits Cyclophosphamide Induced Immunosupression and Oxidative Stress in Mice and also Regulates iNOS and COX-2 Gene Expression in LPS Stimulated Macrophages

The effect of a methanolic extract of Cardiospermum halicacabum L was studied against cyclophosphamide(CTX)-induced toxicity in mice. Administration of CTX (25 mg/kg b.wt, i.p.) for 10 days produced significantmyelosuppression as evidenced by a decreased WBC count and bone marrow cellularity. Co-treatment withCardiospermum significantly increased the total WBC count, bone marrow cellularity and α-esterase positivecells, and the relative organ weights of spleen as well as thymus compared to the CTX alone treated group.Cardiospermum further reduced the enhanced levels of ALP, GPT, LPO, and proinflammatory cytokine TNF-α,and also significantly increased the glutathione (GSH) level in CTX treated animals. The lowered levels ofother cytokines like IFN-γ, IL-2, GM-CSF, after CTX treatment were also found to be increased by extractadministration. Histopathological analysis of small intestine also suggested reduction of CTX-induced intestinaldamage. Moreover the extract down-regulated the inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2(COX-2) mRNA expression in LPS stimulated macrophages. These studies indicate that C. halicacabum couldreduce cyclophosphamide induced oxidative stress and immunosupression through enhancing the antioxidantstatus and immunomodulation by stem cell proliferation.     

Characteristics of Vibrio cholerae O1 isolated from water of the River Ganga,Varanasi, India

Background: Vibrio cholerae is an autochthonous inhabitant of fresh and brackish water and estuarine system. Investigation of V. cholerae from the River Ganga seems important to find variation in CTX arrangement and genomic diversity. Objectives: To investigate V. cholerae O1 strains for the presence of virulence and regulatory genes, variation in number and organisation of the pre-CTXΦ and/or CTXΦ, and for the genomic diversity. Materials and Methods: Polymerase chain reaction (PCR) was used to detect virulence and regulatory genes, type of rstR and location of CTXΦ on the chromosome. Southern hybridisation was conducted to see the number and arrangement of pre-CTXΦ and CTXΦ. Ribotyping and pulsed-field gel electrophoresis were used to find genetic relatedness. Results: Seven strains gave positive results by PCR for the gene encoding for ctxA, zot, ace, tcpA (El Tor), ompU, and toxR, except one strain that was negative for the ctxA. Three strains were positive for the tcpA (El Tor), ompU and toxR genes. Determination of CTX organisation showed that among the ctx-positive strains, four harboured two copies of CTX^ETΦ arranged in tandem and two harboured one copy of CTX^ETΦ, and one ctx-negative strain harboured only one copy of pre-CTX^ETΦ. Pulsotype and ribotype analysis showed existence of at least three pulsotype and ribotypes indicating diversity in genomic content among them. Conclusion: This study thus indicates that multiple clones (ribotypes/pulsotypes) of V. cholerae O1 carrying pre-CTXΦ and/or CTXΦ and ctx-negative strains were present in the water of the River Ganga, Varanasi, India.     

Comparison of drug susceptibility between Escherichia coli detected in stool cultures of patients undergoing transrectal prostate needle biopsy and Escherichia coli in hospital-wide urine antibiograms

A prostate biopsy is essential for prostate cancer diagnosis. However, infections are one of the biopsy-associated complications, and post-biopsy fever is estimated to occur in approximately 1% of all cases. It may thus be beneficial to perform a rectal swab culture before a transrectal prostate biopsy to confirm the presence of resistant bacteria and select preventive antibacterial agents according to the drug susceptibility results. This study aimed to determine whether there is a difference between the drug susceptibility of bacteria detected in the stool of patients who were scheduled to undergo prostate biopsy and the hospital-wide urine antibiogram. Patients suspected of having prostate cancer who underwent transrectal prostate biopsy via transrectal ultrasonography between August 1, 2016, and June 30, 2020, were included in this study. Stool samples were collected and cultured before biopsy. Overall, 99 patients underwent prostate biopsy, and of these, culture results were available for 81 patients (81.8%). Escherichia coli was detected in 74.0% (60 samples) of the stool culture samples, of which 4 samples were extended-spectrum β-lactamase-producing types. We found greater susceptibility of Escherichia coli to ampicillin, fluoroquinolones, sulfamethoxazole/trimethoprim, and cefixime in the stool culture antibiogram than in the hospital-wide urine antibiogram. We also found a significantly low incidence of ESBL-positive Escherichia coli in the stool culture antibiogram with p-values of 0.009, 0.007, and 0.03 compared to the hospital-wide urine antibiograms for 2017, 2018, and 2019, respectively. Stool culture of prostate cancer patients undergoing biopsy may provide useful information for selecting prophylactic antimicrobial agents.     

阴沟肠杆菌6株中产超广谱β内酰胺酶的基因型

目的：研究阴沟肠杆菌6株的超广谱β内酰胺酶(ESBLs)的基因型。方法：分别使用对TEM型、SHV型和CTX-M型基因特异的引物,PCR扩增6株阴沟肠杆菌接合子Esbl基因,对PCR产物直接测序分析其基因型。结果：3株阴沟肠杆菌的接合子均含有CTX—M-3型酶,同时含有TEM型酶。另3株阴沟肠杆菌接合子均含有一种等电点为8．3未知的β内酰胺酶,同时含有一种pI为5．4或5．5未知的β内酰胺酶。结论：临床分离的阴沟肠杆菌可产CTX-M-3型酶,对头孢菌素类产生耐药性。     

抗ENO1抗体联合二甲双胍通过靶向肿瘤干细胞逆转人非小细胞肺癌A549细胞对西妥昔单抗的抵抗

目的:探究抗烯醇化酶1 (enolase 1,ENO1)抗体、二甲双胍(metformin,MET)通过靶向肿瘤干细胞对西妥昔单抗(cetuximab,CTX)耐药型非小细胞肺癌A549细胞增殖、迁移、侵袭和干性的影响及其可能的作用机制.方法:10 mmol/L MET联合40μg/ml抗ENO1抗体处理CTX(35 ...     

头孢噻肟溶液稳定性研究

本文采用紫外分光光度法对 CTX 溶液的含量及稳定性进行了实验研究。结果表明:该方法简便可行,本品最大吸收峰在234nm(±1nm)处,CTX 溶液在 pH 3.7—8.0之间稳定,有效期为2.1天,与5%葡萄糖液、10%葡萄糖液、5%葡萄糖氯化钠液、林格氏液、0.9%NaCl 液配伍(25℃),在48小时内含量变化不大,可以联合应用。     

环丙沙星与氧氟沙星注射液治疗细菌性感染的疗效观察

以乳酸环丙沙星（ＣＰＬＸ）注射液和氧氟沙星（ＯＦＬＸ）注射液随机分组治疗各种细菌性感染４０例及４２例，并以注射用头孢噻肟钠（ＣＴＸ）治疗４９例作对照。三组平均年龄、体重、疗程及病情程度相比无显著性差异，具可比性。病种分布以消化道感染最多，共８１例，占总数的６１．８％。三组１３１例病人细菌阳性率为９４．７％。一疗程ＣＰＬＸ组、ＯＦＬＸ组、ＣＴＸ组治愈率分别为８７．２％、８３．３％、７１．４％，有效率     

眼镜蛇毒细胞毒素CTX-d的分离纯化及抗肿瘤活性

目的 分离纯化眼镜蛇毒细胞毒素,测定其体内外抗癌作用.方法 应用柱层析及RP-HPLC,从眼镜蛇毒粗毒中分离纯化细胞素素(CTX).体内外抗癌作用利用噻唑兰(MTT)法及对荷瘤小鼠U14瘤的抑瘤作用.结果 分离纯化获得的CTX-d不混有PLA2,在体内外实验中显示明显的抗肿瘤作用.结论 结合阳离子交换层析和RP-HPLC可从眼镜蛇毒中高效分离获得不含PLA2的CTX.     

Biochemical markers in oncology. Part I: molecular basis. Part II: clinical uses

The investigation of the molecular mechanisms involved in carcinogenesis and tumor progression has led to the development of numerous biochemical markers. Biochemical markers may serve for early prediction of tumor recurrence, progression and development of metastases including bone metastases and for prediction of response to therapy. Tumor antigens have been used for more than a decade and although they have shown promising clinical results, their sensitivity and specificity remain limited. A lot of knowledge on the key molecules which control cell cycle, apoptosis and angiogenesis has been acquired during recent years, but their clinical value remains uncertain. Molecular markers which are linked to malignant transformation may provide a non-surgical therapeutic approach by targeting these molecules through gene therapy or antisense molecules. Because of the complexity of the physiopathogical processes involved in tumorogenesis and metastases, we first provide a review on the molecular basis of the various tumor markers and then discuss their potential clinical utility for the major cancers. The review of the current literature indicates that at the exception of a few examples, such as the use of Her-2 to predict response of the targeted Herceptin therapy, no single marker is sensitive and specific enough to perform an accurate diagnosis, predict disease progression or response to treatment. A combination of different biochemical and imaging markers appears to be the most promising strategy to monitor patients with cancer.     

Immunomodulatory effects of diclofenac in leukocytes through the targeting of Kv1.3 voltage-dependent potassium channels

Kv1.3 plays a crucial role in the activation and proliferation of T-lymphocytes and macrophages. While Kv1.3 is responsible for the voltage-dependent potassium current in T-cells, in macrophages this K⁺ current is generated by the association of Kv1.3 and Kv1.5. Patients with autoimmune diseases show a high number of effector memory T cells that are characterized by a high expression of Kv1.3 and Kv1.3 antagonists ameliorate autoimmune disorders in vivo. Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) used in patients who suffer from painful autoimmune diseases such as rheumatoid arthritis. In this study, we show that diclofenac impairs immune response via a mechanism that involves Kv1.3. While diclofenac inhibited Kv1.3 expression in activated macrophages and T-lymphocytes, Kv1.5 remained unaffected. Diclofenac also decreased iNOS levels in Raw 264.7 cells, impairing their activation in response to lipopolysaccharide (LPS). LPS-induced macrophage migration and IL-2 production in stimulated Jurkat T-cells were also blocked by pharmacological doses of diclofenac. These effects were mimicked by Margatoxin, a specific Kv1.3 inhibitor, and Charybdotoxin, which blocks both Kv1.3 and Ca²⁺-activated K⁺ channels (K_Ca3.1). Because Kv1.3 is a very good target for autoimmune therapies, the effects of diclofenac on Kv1.3 are of high pharmacological relevance.