Preparation,physicochemical characterization and biological evaluation of cefodizime metal ion complexes

Objectives Cefodizime is a broad spectrum cephalosporin belonging to the third generation agents. In this study, attention has been paid to the preparation, physicochemical characterization and biological evaluation of new Cu²⁺, Zn²⁺, Fe³⁺, Co²⁺ and Al³⁺ complexes of cefodizime. Methods The stoichiometrics and the mode of bonding of the complexes were deduced from their elemental and metal analysis, electrical conductivity measurements, UV‐vis, infrared and Raman spectroscopic investigations. Study of the stoichiometry of these complexes referred to the formation of 1: 1 ratios of metal to ligand. Antimicrobial activity of the complexes was determined using two strains of Gram‐positive (Bacillus subtilis and Proteus vulgaris) and two strains of Gram‐negative (Escherichia coli W3110 and Pseudomonas putida) bacteria. The minimal inhibitory concentration was determined as the lowest concentration inhibiting bacterial growth on solid Luria Bertani medium. Key findings The spectra gave evidence as to the position of binding. In addition, the aqueous solubility of cefodizime was strongly reduced by complexation. Conclusions The antibacterial activity of cefodizime was not affected by complexation with Al³⁺ but it was reduced by complexation with the other tested metal ions against the bacteria under study.     

Reduction of catheter-related colonisation by the use of a silver zeolite-impregnated central vascular catheter in adult critical care

Central vascular catheters (CVC) are used extensively in critical care for monitoring and therapy. They can become colonised with viable micro-organisms within 24 h of insertion, which can rapidly form biofilm. This colonisation is a precursor of catheter-related bloodstream infections (CR-BSI), which are associated with substantial morbidity, mortality, prolonged hospital stay and increased cost. Antimicrobials have been incorporated into the bulk material of CVC or applied to their surfaces as a coating in an attempt to reduce the incidence of CVC colonisation and infection. This study examines the effect of a silver zeolite-impregnated catheter on catheter-related colonisation and infection in adult critical care patients. The study was conducted in adult Intensive Care Units (ICU) at three acute hospitals over 14 months and involved 246 CVC insertions (122 silver-impregnated and 124 non-impregnated). CVC tip colonisation was detected by the Maki Roll culture and CR-BSI by differential time-to-positivity of blood cultures. Overall colonisation rate was significantly lower in the silver zeolite-impregnated CVC tips (58%) as compared with the control CVC tips (73%) (p<0.025). In addition, there was a lower rate (34%) of tip colonisation by coagulase negative staphylococci in the silver zeolite-impregnated CVC tips as compared with the control CVC tips (47%) (p<0.05). Four episodes of CR-BSI were detected in each arm by differential time-to-positivity in a subset of patients. This study indicates that the silver zeolite-impregnated catheter is superior to non-impregnated catheter in reducing the rate of CVC colonisation but it showed no difference in the rates of CR-BSI in the two arms. Larger prospective randomised control studies are required to evaluate its role in the prevention of CR-BSI.     

Physiological changes in the critically ill patient with sepsis

Intensive care medicine deals with the critically ill; these patients usually have multiple organ failure, and complex medical conditions. The mortality in Australia and New Zealand among this population is approximately 16.1%, with approximately 24.2% having existing co-morbidities, and 23.4% of these patients experiencing sepsis or septic shock. Sepsis is a clinical syndrome that traditionally was regarded as a physiological maladaptive response to a foreign pathogen and ranges in disease severity from simple sepsis to septic shock, a life threatening condition, associated with multiple organ failure. Sepsis has profound effects on all systems of the body, and most notably the cardiovascular, renal and hepatic systems. There has been much research into the septic critically ill patient and recent developments in basic pharmacology and physiology has yielded results applicable to clinical practice. Sepsis may induce a state of increased cardiac output, which has significant effects on drug pharmacokinetics and pharmacodynamics. This increased cardiac output increases both renal and hepatic blood flow, and alters rates of antibiotic metabolism, and excretion. There are also alterations in the fluid compartments of the septic critically ill, that results in an altered volume of distribution, and ultimately decreased antibiotic concentrations at their site of action. This article will examine and review in detail the septic critically ill patient, and the effects that sepsis has on physiology and the resulting altered antibiotic pharmacokinetics and pharmacodynamics. Current knowledge suggests that the medical prescriber should be weary of antibiotic dosing in the septic critically ill, and consider alternative dosing regimes that are individualized to the patient in order to maximize efficacy.     

Implications of understanding cancer stem cell (CSC) biology in head and neck squamous cell cancer

Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of this disease. Efforts are ongoing throughout the world to improve early detection and prevention of HNSCCs. Often, treatment fails to obtain total cancer cure and this is more likely with advanced stage disease. In recent years it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells (CSC) that 'escape' currently available therapies. CSCs form a minute portion of the total tumour burden but may play a disproportionately important role in determining outcomes. Molecular mechanisms which underlie the genesis of CSCs are yet not fully understood and their detection within the total tumour bulk remains a challenge. Specific markers like Aldehyde dehydrogenase 1 (ALDH1), CD44 and Bmi-1 have shown early promising results both in CSC detection and in guiding treatment protocols. CSCs have been shown to be relatively resistant to standard treatment modalities. It is hoped that developing robust in vitro and in vivo experimental models of CSCs might provide a means of devising more effective therapeutic strategies.     

Radiopharmaceuticals: when and how to use them to treat metastatic bone pain

Bone pain due to skeletal metastases constitutes the most common type of cancer-related pain. The management of bone pain remains challenging and is not standardized. In patients with multifocal osteoblastic metastases, systemic radiopharmaceuticals should be the preferred adjunctive therapy for pain palliation. The lack of general knowledge about radiopharmaceuticals, their clinical utility and safety profiles, constitutes the major cause for their underutilization. Our goal is to review the indications, selection criteria, efficacy, and toxicities of two approved radiopharmaceuticals for bone pain palliation: strontium-89 and samarium-153. Finally, a brief review of the data on combination therapy with bisphosphonates or chemotherapy is included.     

Serum levels of β-catenin as a potential marker for genotype 4/hepatitis C-associated hepatocellular carcinoma

The global rising incidence of hepatocellular carcinoma (HCC), which parallels the increase of hepatitis C virus (HCV) prevalence, has sparked a renewed interest in discovering additional HCC serum markers. In this study, we investigated the clinical use of serum E-cadherin, ICAM, MMP-2, VEGF, OPN and β-catenin as potential diagnostic makers for HCV/genotype 4-associated HCC. Twenty cases of healthy subjects, 11 cases with asymptomatic HCV/genotype 4 carriers (ASC), 28 chronic hepatitis (CH) cases and 32 patients with HCC were enrolled in this study. Serum levels of proteins were measured by a sandwich-enzyme-linked (ELISA) assay. The diagnostic accuracy of each candidate marker was evaluated using receiver-operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). We demonstrated that serum β-catenin levels were significantly elevated in patients with HCC compared to those with CH, ASC and healthy controls. Among the six studied markers, β-catenin was also found to be the only marker that can significantly discriminate between patients with HCC and those with CH; therefore, β-catenin could be considered as a potential marker for early diagnosis of HCV-associated HCC in patients infected with HCV genotype 4.     

Accumulation and Depuration of Trace Metals in Southern Toads, Bufo terrestris, Exposed to Coal Combustion Waste

Accumulation and depuration of metals by an organism are underrepresented in the literature. We collected southern toads (Bufo terrestris) from coal by-product (ash)-contaminated and uncontaminated sites to examine metal concentrations over time. Toads were placed in four exposure regimes, then sacrificed periodically over a 5-month period, and whole-body metal levels were measured. Toads exposed to ash accumulated significant concentrations of metals. Metal concentrations changed throughout the experiment, and profiles of accumulation and depuration differed depending on the metal and exposure regime. Ash-exposed toads exhibited elevated levels of 11 of 18 metals measured. Increases ranged from 47.5% for Pb to more than 5000% for As. Eight of 18 metals did not change in control toads, while 10 of 18 metals decreased in toads removed from ash, ranging from −25% for Co to −96% for Tl. Seven metals that decreased in toads removed from ash did not change in control toads.     

The role of nurses and midwives in polio eradication and measles control activities: a survey in Sudan and Zambia

Background  

Nurses and midwives are the key providers of nursing and midwifery services; in many countries, they form the major category of frontline workers who provide both preventive and curative services in the community. When the skills and experience of nursing and midwifery personnel are maximized, they can contribute significantly to positive health outcomes. We conducted a survey among nurses and midwives working at district level in Sudan and Zambia to determine their roles and functions in polio eradication and measles elimination programmes.     

Pathways of renal injury in systemic gram-negative sepsis

Acute renal failure is a grave complication of systemic gram-negative sepsis. The pathophysiological mechanisms of sepsis leading to kidney injury result in part from systemic inflammatory and haemodynamic alterations. These are triggered by the interaction of endotoxin with Toll-like receptor 4 (TLR4) on cells of the immune system. Recently, TLR4 and other co-effector molecules were identified on renal tubular and vascular cells. Furthermore, it was demonstrated that systemic endotoxin has direct access to renal sites where these receptors are expressed. Therefore, we review data in support of this novel pathway of renal injury in sepsis, whereby systemic endotoxin causes direct injury through interactions with local epithelial and endothelial TLR4.     

Type 2 diabetes-associated androgen alteration in patients with erectile dysfunction

Our objective was to assess the pattern of type-2 diabetes-associated androgen alteration in patients with erectile dysfunction (ED). A total of 127 diabetic male patients with ED were enrolled in this study. Erectile function was assessed using the International Index of Erectile Function (IIEF). At the time of assessment, patients were also interviewed and assessed for socio-demographic and medical history that includes duration and severity of diabetes mellitus (DM). Patients underwent routine laboratory investigations, in addition to total testosterone (T), dehydroepiandrosterone sulphate (DHEA-S) and insulin assessment. The mean age +/- SD was 53.8 +/- 9.3 years. Of patients 25.2% (n = 32/127), 6.3% (n = 8/127) and 31.5% (n = 40/127) had low total T, low DHEA-S and hyperinsulinaemia respectively. There were significant association between the increase in age and body mass index and the presence of low T level. Of the patients 37.5% (n = 12/32) with low T level had glycosylated haemoglobin (HbA1c) >7% while, 22.1% (n = 21/95) of the patients with normal T level had HbA1c >7% (p < 0.05). There were significant associations between the number of patients with low level of total T or DHEA-S and poor control of DM. Patients with low T level were two times more likely (56.3%, n = 18/32) to have severe ED than patients with normal T level (27.4%, n = 26/95) (p < 0.01). There were significant differences between the mean levels of total T or DHEA-S and poor control of DM. No significant associations were detected between hyperinsulinaemia and the level of fasting blood sugar, duration of DM, metabolic control of DM or ED severity. Patients with low T level were three times as likely to have hyperinsulinaemia as those patients with normal T level (p < 0.05). The current study clearly demonstrated that there were significant associations between low level of total T or DHEA-S and poor control of DM.