Antibiotic resistance. An impending crisis

The global emergence of antimicrobial resistance has become a pre-eminent concern in medicine and public health. Antimicrobial resistance is of particular concern because the problem is widespread, the causative factors are uncontrolled, and national strategies to address the problem are lacking. The persisting burden of infectious diseases makes elimination of antibiotic use unethical, but dramatic overuse and misuse of antimicrobial agents around the world must be reduced to extend the useful lifetimes of these drugs. Population genetic models suggest that resistance emerges rapidly under the selective pressure of antibiotics, but decays slowly once that pressure is removed. Hence, measures to prevent the emergence of resistance must be implemented urgently. A multiplicity of factors drive antibiotic resistance, and solutions require the collaboration of governmental agencies, the pharmaceutical companies, healthcare providers, and consumers. Leadership in the form of a national steering committee on antimicrobial resistance is needed in the Kingdom of Saudi Arabia to guide collective action to control the threat of antibiotic resistance.     

Hypospadias trends in two US surveillance systems

OBJECTIVE: Hypospadias is a common congenital anomaly, the cause of which is unknown. Unexplained increases in the rates of hypospadias occurred in five European countries in the 1970s and 1980s. We examined data from two birth defects surveillance systems in the United States for evidence of similar trends. METHODOLOGY: The Metropolitan Atlanta Congenital Defects Program (MACDP) provided birth prevalence rates from 1968 to 1993. The nationwide Birth Defects Monitoring Program (BDMP) provided rates from 1970 to 1993. MACDP data are population-based and could be categorized by the severity of the hypospadias. BDMP data allowed analysis of rate trends for the four census regions of the United States. RESULTS: Data from both surveillance systems showed an approximate doubling of hypospadias rates in the 1970s and 1980s. MACDP data showed that the rate of severe cases increased while the ratio of mild to severe cases decreased. BDMP data showed that hypospadias rates increased markedly in all four regions of the United States. CONCLUSIONS: The observed increases are unlikely to be attributable to increased sensitivity of the surveillance systems or the identification of more mild cases by physicians over time, because either trend would have increased rather than decreased the ratio of mild to severe cases. If real, these trends represent the largest number of cases and the first report of an increase in hypospadias rates outside of Europe. Additional investigation of a possible increase in hypospadias rates is warranted.     

Black tea and mammary gland carcinogenesis by 7,12- dimethylbenz[a]anthracene in rats fed control or high fat diets

Epidemiological studies suggest that tea may reduce cancer risk, and in laboratory rodents, chemopreventive effects of tea or purified extracts of tea have been demonstrated in lung, gastrointestinal tract and skin. There is some evidence of chemoprevention by tea in the mammary gland, but the data are not conclusive. In order to evaluate more fully the possible influence of black tea on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary gland tumors in the female S-D (Sprague-Dawley) rat, three large studies were performed: experiment 1, tumorigenesis in rats fed AIN-76A diet and given 25 mg/kg DMBA and 1.25 or 2.5% whole tea extract or water to drink; experiment 2, tumorigenesis in rats given 15 mg/kg DMBA and the same diet and fluids as in experiment 1; experiment 3, tumorigenesis in rats fed control or HF (high fat, corn oil) diet and given 15 mg/kg DMBA and 2% tea or water to drink. Tea was given throughout the experiment; DMBA was given by gastric gavage at 8 weeks of age. There was no consistent effect of tea on tumorigenesis in rats fed AIN-76A diet; there was, however, evidence in experiment 3 of a reduction of tumorigenesis by tea in rats fed the HF diet. In experiment 3, rats fed the HF diet and given water showed the expected increase in tumor burden (number and weight) compared with rats fed control diet. However, rats fed the HF diet and given 2% tea showed no increase in tumor burden; their tumor burden was significantly lower than in rats fed the HF diet and given water (P < 0.01) and was not different from rats fed control diet and given water or tea. In addition, in experiment 3, the number of malignant tumors per tumor- bearing rat was increased by the HF diet in water-drinking rats (P < 0.01) but not in tea-drinking rats. Therefore, it appears that tea partially blocked the promotion of DMBA-induced mammary tumorigenesis by the HF diet.      

Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA vaccine

The nucleocapsid （N） protein of SARS-coronavirus （SARS-CoV） is the key protein for the formation of the helical nucleocapsid during virion assembly. This protein is believed to be more conserved than other proteins of the virus, such as spike and membrane glycoprotein. In this study, the N protein of SARS-CoV was expressed in Escherichia coli DHSalpha and identified with pooled sera from patients in the convalescence phase of SARS. A plasmid pCI-N, encoding the full-length N gene of SARS-CoV, was constructed. Expression of the N protein was observed in COS1 cells following transfection with pCI-N. The immune responses induced by intramuscular immunization with pCI-N were evaluated in a murine model. Serum anti-N immunoglobutins and splenocytes proliferative responses against N protein were observed in immunized BALB/c mice. The major immunoglobulin G subclass recognizing N protein was immunoglobulin G2a, and stimulated splenocytes secreted high levels of gamma interferon and IL-2 in response to N protein. More importantly, the immunized mice produced strong delayed-type hypersensitivity （DTH） and CD^8＋ CTL responses to N protein.     

Contrast column interruption artefact in computed tomography pulmonary angiography

Interruption of the contrast column during inspiration can lead to non‐diagnostic CT pulmonary angiograms. The importance of this artefact will increase with more CT studies being performed for pulmonary embolism on multidetector row CT. We describe here an instance of such an artefact and discuss its aetiology.     

Incidental heterotopic pregnancy demonstrated on magnetic resonance imaging

We report a case of an assisted pregnancy in an asymptomatic woman who was found to have an extrauterine mass on ultrasound and MRI. This complex mass had equivocal imaging features and was found to be a ruptured ovarian ectopic pregnancy at surgery. This case illustrates that vigilance is required regarding the possibility of coexisting ectopic and intrauterine pregnancy following assisted conception, even in entirely asymptomatic cases.     

灯盏花素对豚鼠单一心室肌细胞ICa的抑制作用

目的：观察灯盏花素对豚鼠单一心室肌细胞钙离子电流（ＩＣａ）的影响。方法：应用全细胞膜片钳制技术。结果：灯盏花素能明显抑制心室肌细胞的Ｃａ＾２＋通道,使ＩＣａ减小。此作用有明显的电压依赖性。在峰电流电压下作用最明显,而对其反转电位无明显影响。在指令电位０ｍＶ时,０．５ｍｇ％灯盏花素使ＩＣａ减小５．４％,１ｍｇ％灯盏花素使ＩＣａ减小２２．９％（Ｐ〈０．０１）,２ｍｇ％灯盏花素使ＩＣａ减小４５．０％（Ｐ     

3－硝基－1，2，4－三唑类乏氧细胞放射增敏剂的构效关系

为了寻找毒性低、增敏作用强的乏氧细胞放射增敏剂，设计并合成了一系列５－溴－，５－甲基－，和５－未取代的３－硝基－１，２，４－三唑－１－乙酰胺类化合物，用ＨｅＬａＳ３细胞进行了体外试验。结果表明５－溴取代衍生物的增敏作用强于相应的５－甲基－或５－未取代的硝基三唑衍生物，但是它们的毒性亦增大。修饰１位乙酰胺侧链也可以改变化合物的增敏作用和亲脂性。在所测定的化合物中ＴＡ－１０１［２－（３－硝基－１－三唑基）乙酰胺］由于有高的增敏作用和低亲脂性，可能是一个有希望的放射增敏剂。     

Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay

Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M1- dG have not been applied to a large number of individuals or variety of samples. Often, only a few microg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M1-dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of MI-dG in 1 microg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M1-dG per 10(8) normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/32P-post- labelling (HPLC/PPL) method previously developed and indicated a high correlation between M1-dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 microg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.      

Ureteric complications in recipients of kidneys from donation after circulatory death donors

A large increase in the use of kidneys from donation after circulatory death (DCD) donors prompted us to examine the impact of donor type on the incidence of ureteric complications (UCs; ureteric stenosis, urinary leak) after kidney transplantation. We studied 1072 consecutive kidney transplants (DCD n=494, live donor [LD] n=273, donation after brain death [DBD] n=305) performed during 2008‐2014. Overall, there was a low incidence of UCs after kidney transplantation (3.5%). Despite a trend toward higher incidence of UCs in DCD (n=22, 4.5%) compared to LD (n=10, 3.7%) and DBD (n=5, 1.6%) kidney transplants, donor type was not a significant risk factor for UCs in multivariate analysis (DCD vs DBD HR: 2.33, 95% CI: 0.77‐7.03, P=.13). There was no association between the incidence of UCs and donor, recipient, or transplant‐related characteristics. Management involved surgical reconstruction in the majority of cases, with restenosis in 2.7% requiring re‐operation. No grafts were lost secondary to UCs. Despite a significant increase in the number of kidney transplants from DCD donors, the incidence of UCs remains low. When ureteric complications do occur, they can be treated successfully with surgical reconstruction with no adverse effect on graft or patient survival.