D-ribose-L-cysteine exhibits restorative neurobehavioral functions through modulation of neurochemical activities and inhibition oxido-inflammatory perturbations in rats exposed to polychlorinated biphenyl.

Polychlorinated biphenyl (PCB) is potentially harmful environmental toxicant causing cognitive decline with depressive features. PCB-induced behavioral deficits are associated with neurochemical dysfunctions, immune changes, and oxidative stress. This study investigated the neuroprotective effects of D-ribose-L-cysteine (DRLC), a neuroprotective precursor element of glutathione on PCB-induced neurobehavioral impairments. Following the initial 15 days of PCB (2 mg/kg) exposure to rats, DRLC (50 mg/kg) was given orally for an additional 15 days, from days 16 to 30. Animals were assessed for behavioral effect such as changes in locomotion, cognition, and depression. Oxidative/nitrergic stress markers; antioxidant regulatory proteins paraoxonase-1 (PON-1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nfr2), NADPH oxidase-1 (NOX-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and neuroinflammation (NF-kß, and TNF-α); and neurochemical metabolizing enzymes (acetylcholinesterase (AChE), monoamine oxidase-A and -B (MAO-A, MAO-B)) were carried out. The PCB-induced decline in locomotion, cognitive performance, and depressive-like features were reversed by DRLC. More specifically, PCB-induced oxidative and nitrergic stress, typified by reduced levels GSH, CAT, and SOD, accompanied by elevated MDA and nitrite were attenuated by DRLC. Additionally, DRLC restored the neuroinflammatory milieu indicated by decreased NF-kß and TNF-α levels toward normal. Hyperactivities of AChE, MAO-A, MAO-B, PON-1, and NOX-1 levels as well as Nfr2, NQO1, and PON-1 due to PCB exposure were mitigated by DLRC. Our results suggest DRLC as a prospective neurotherapeutic agent against PCB-induced neurobehavioral impairments such as cognitive deficit and depressive-like feature through antioxidative and anti-nitrergic stress, anti-neuroinflammation, inhibition of brain metabolizing enzymes, and normalization of neurochemical homeostasis.

Targeting nuclear factor-kappa B to overcome resistance to chemotherapy.

Intrinsic or acquired resistance to chemotherapeutic agents is a common phenomenon and a major challenge in the treatment of cancer patients. Chemoresistance is defined by a complex network of factors including multi-drug resistance proteins, reduced cellular uptake of the drug, enhanced DNA repair, intracellular drug inactivation, and evasion of apoptosis. Pre-clinical models have demonstrated that many chemotherapy drugs, such as platinum-based agents, antracyclines, and taxanes, promote the activation of the NF-κB pathway. NF-κB is a key transcription factor, playing a role in the development and progression of cancer and chemoresistance through the activation of a multitude of mediators including anti-apoptotic genes. Consequently, NF-κB has emerged as a promising anti-cancer target. Here, we describe the role of NF-κB in cancer and in the development of resistance, particularly cisplatin. Additionally, the potential benefits and disadvantages of targeting NF-κB signaling by pharmacological intervention will be addressed.

Prevalence and antimicrobial resistance pattern of Salmonella in animal feed produced in Namibia.

The occurrence of Salmonella is a global challenge in the public health and food production sectors. Our study investigated the prevalence, serovar and antimicrobial susceptibility of strains of Salmonella serovars isolated from animal feed (meat-and-bone and blood meal) samples from two commercial abattoirs in Namibia. A total of 650 samples (n=650) were examined for the presence of Salmonella. Results showed that 10.9% (n=71) were positive for Salmonella. Of the Salmonella serovars isolated, S. Chester was the most commonly isolated serovar (19.7%), followed by S. Schwarzengrund at 12.7%. From the Salmonella isolates, 19.7% (n=14) were resistant to one or more of the antimicrobials (nalidixic acid, trimethoprim-sulfamethoxazole, sulfisoxazole, streptomycin and/or tetracycline), whereas 80.3% (n=57) were susceptible to all 16 antimicrobials tested. Resistance to sulfisoxazole and the trimethroprimsuflamethoxazole combination were the most common. The resistant isolates belonged to ten different Salmonella serovars. The susceptibility of most of the Salmonella isolated to the antimicrobials tested indicates that anti-microbial resistance is not as common and extensive in Namibia as has been reported in many other countries. It also appears that there is a range of antimicrobials available that are effective in managing Salmonella infections in Namibia. However, there is some evidence that resistance is developing and this will need further monitoring to ensure it does not become a problem.

Gram staining in the diagnosis of acute septic arthritis.

This study aimed at determining the sensitivity and specificity of Gram staining of synovial fluid as a diagnostic tool in acute septic arthritis. A retrospective study was made of 22 patients who had arthroscopic lavage following a provisional diagnosis of acute septic arthritis of the knee joint. Gram stains and cultures of the knee aspirates were compared with the clinical and laboratory parameters, to evaluate their usefulness in diagnosing acute arthritis. All patients who had septic arthritis had pain, swelling and limitation of movement. CRP was elevated in 90% of patients. The incidence of elevated white blood cell count was higher in the group of patients with a positive Gram stain study (60%) as compared to patients with a negative Gram stain study (33%). Gram staining sensitivity was 45%. Its specificity was however 100%. Gram staining is an unreliable tool in early decision making in patients requiring urgent surgical drainage and washout.

Cryptosporidium meleagridis from humans: molecular analysis and description of affected patients.

OBJECTIVES: To genetically characterize an unusual genotype of Cryptosporidium from the stools of humans with diarrhoea and to identify risk factors in the affected patients. METHODS: DNA was extracted from human faeces where Cryptosporidium oocysts were detected by light microscopy. Cryptosporidial gene fragments from six different loci were analysed by PCR alone, PCR/RFLP and by DNA sequencing. Oocysts were characterized by light and immunofluorescence microscopy and epidemiological data was collected from the affected patients. RESULTS: Analysis of the Cryptosporidium oocyst wall protein (COWP) gene amplified from > 2000 human faecal samples identified 19 patients all of which produced an unusual RFLP profile. Subsequent DNA sequence analysis of this and an additional four genetic loci (including 18S rRNA sequences) confirmed these as a homogeneous group which was genetically distinct from Cryptosporidium parvum. The isolates were identified as Cryptosporidium meleagridis since the gene sequences were identical to those from this species recovered from birds. Conventional microscopy showed oocysts indistinguishable from C. parvum and reacted strongly with two different commercially available anti-oocyst monoclonal antibodies. None of the patients showed risk factors unusual for cryptosporidiosis; however, ten of the cases occurred during the summer/autumn, six had a history of foreign travel, four were co-infected with Giardia, two were HIV positive, and six were without identifiable immunocompromising factors. CONCLUSIONS: This study further confirms that C. meleagridis, in addition to C. parvum, is involved in human disease. The study also highlights the lack of basic information on the host range of this genus of parasites, the complexity of the transmission routes involved in human cryptosporidiosis, and the value of molecular techniques in identify hitherto unrecognised differences in Cryptosporidium from human faeces.

Blood-borne virus-related discrimination in dental services.

While the risk of infection through occupational exposure to blood-borne viruses is a major concern of dental health care workers, the National HIV/AIDS Strategy and many health, AIDS and discrimination-related agencies have identified discrimination related to HIV/AIDS as a priority area for action. In 1995 the Commonwealth Department of Health and Family Services selected the School of Medical Education at the University of New South Wales to conduct a national project to reduce discrimination related to blood-borne viruses within dental services (Godwin, Meihubers & Rotem 1997). This paper provides an overview of the study and its major findings. The study focused on quality of care issues which may cause or manifest discrimination. Key stakeholders were invited to review policies, procedures, organisational arrangements and other systemic issues which influence the quality of oral health services to populations within selected geographical regions.

A prospective audit of wound infection rates after caesarean section in five West Yorkshire hospitals.

A three month prospective audit of wound infection following emergency and elective caesarean section was carried out in five West Yorkshire hospitals. Among 4076 women undergoing delivery in the five obstetric departments, the caesarean rate was 15.4%. The overall infection rate was 45/628 (7.2%) with a range of 2.5-17.2% between the five centres. The infection rate was 14/226 (6.2%) when antibiotics were used compared with 31/402 (7.7%) without antibiotics. The use of prophylactic antibiotics made no significant difference to the infection rate, which did not correlate with duration of labour or of ruptured membranes. The number of vaginal examinations correlated with the infection rate. In conclusion, the caesarean section rate observed was higher than that estimated for the UK as a whole, but was distorted by one centre with a high rate. For the other four hospitals the caesarean rate was unexceptional. The ratio of emergency to elective operations was comparable with recently reported values in the UK and the wound infection rate was within the widely varying limits found in previous studies. In view of the relatively low infection rate recorded without antibiotics, in the interests of cost effectiveness, prophylaxis may be limited in future to selected women at high risk. Because this was an audit rather than a randomized study we cannot exclude that this is already happening on an empirical basis.

Becoming a GP facilitator. A training approach.

The UNSW School of Medical Education has devised a training program for general practitioners to develop skills as GP facilitators involved with small groups in Continuing Medical Education programs and was offered in 1994. This program was well received by the participants and further developments are under way. Prior research on the most effective CME strategies for general practitioners confirms the value of this approach.

Acute pouchitis and deficiencies of fuel.

PURPOSE: Acute pouchitis is a troublesome complication after restorative proctocolectomy. Deficiency of fuel, especially short chain fatty acids (SCFA), produced by anaerobic bacterial fermentation of saccharides, is implicated in ulcerative and diversion colitis. Our hypothesis was that SCFA deficiency occurs in acute pouchitis, and correction of the deficiency is associated with resolution of pouchitis. METHODS: Thirty-two patients were studied, 10 with histologically confirmed acute pouchitis and 22 with healthy pouches. Stool concentrations of SCFA (acetic, propionic, butyric, and valeric acids) were determined by gas-liquid chromatography. Quantitative bacteriologic studies of stool were carried out, and four-quadrant pouch biopsies were assessed by a pathologist who was unaware of the clinical state. Patients with pouchitis were treated for six weeks with metronidazole and given dietary advice to increase their intake of fermentable saccharides. RESULTS: Stool concentrations of SCFA were significantly less in pouchitis patients compared with patients with healthy pouches (340 mumol/g (range, 124-492) vs. 93 (range, 44-136) P < 0.01). No differences in anaerobic or aerobic counts were seen. Resolution of pouchitis was associated with a significant increase in SCFA, but anaerobic counts fell. CONCLUSION: Deficiency of SCFA is implicated in acute pouchitis.

Carriage of adhesive Escherichia coli after restorative proctocolectomy and pouch anal anastomosis: relation with functional outcome and inflammation.

Restorative proctocolectomy with pelvic ileal reservoir is a well accepted option for the surgical treatment of ulcerative colitis. Acute pouchitis is a common complication and resembles acute ulcerative colitis. Patients with ulcerative colitis carry Escherichia coli that adhere to epithelial cells and thus this study examined whether acute pouchitis is associated with the carriage of adhesive E coli. E coli isolated from stool samples from 24 patients (median age 34 years, range 16-64; 13 men, 11 women) who had had restorative proctocolectomy with pelvic ileal reservoir were examined by means of the buccal epithelial cell adhesion assay. Patients were studied at a median of 12 months (range 7-21) after operation. Eight of 24 patients had acute pouchitis at the time of study. Adhesive E coli were detected in nine of 24 patients with a pelvic ileal reservoir compared with none of 12 controls (p < 0.05). The buccal epithelial cell adhesion index was inversely related to the degree of acute pouchitis (rs = 0.46, p = 0.024) and to the functional outcome (rs = -0.49, p = 0.022). Carriage of adhesive E coli was not related to the design of the reservoir. By contrast with ulcerative colitis, acute pouchitis is not associated with the carriage of adhesive E coli.

Does earwax lose its pathogens on your auriscope overnight?

OBJECTIVES: To describe the organisms cultured from general practitioners' auriscope earpieces; and to explore general practitioners' perceptions of the possibility of cross infection from contaminated auriscope earpieces and of how their auriscope earpieces are cleaned. DESIGN: Microbiological survey of auriscope earpieces in two general practices and a semistructured questionnaire sent to 105 general practitioners. SETTING: General practitioners served by one district general hospital microbiology laboratory in the north of England. RESULTS: Organisms were cultured from 41 (93%) of 44 auriscope earpieces, of which 14 (32%) carried potential pathogens; four (9%) were heavily contaminated. Of the 85 (81%) general practitioners who responded, 72 (85%) believed that contaminated auriscope earpieces could cause serious infection, 66 (78%) did not clean earpieces between patients, and 70 (82%) thought that patients would mind if they knew that dirty earpieces were used. CONCLUSIONS: Almost a third of auriscope earpieces were contaminated by pathogenic bacteria. Although general practitioners suspected this, most did not ensure that a clean earpiece was used for each patient.

Reducing bruising after venepuncture.

Bruising after venepuncture is undesirable. To verify an apparent increase in bruising after introducing a new venepuncture system in a small district general hospital and to improve the venepuncture service two prospective audits of the incidence and severity of bruising after venepuncture were performed in two groups of 100 consecutive inpatients undergoing venepuncture by phlebotomists. In the first audit bruising was detected in 45 patients, of whom 34(76%) had bruises > 100 mm2 in area. After modification of the technique, whereby the phlebotomists ensured that haemostasis had been attained before leaving the patient, bruising was significantly reduced, occurring in 25 patients only 9 of whom (36%) had bruises > 100mm2 in area (both p < 0.01) in the second audit. Monitoring of standards and simple modification of technique resulted in significant reduction in incidence and severity of bruising, improving the quality of the venepuncture service.

Influence of myectomy, ileal valve, and ileal reservoir on the ecology of the ileum.

Fecal bacteriology, fecal volatile fatty acids, and ileal mucosal morphology were studied in dogs after ileoanal anastomosis alone, ileoanal anastomosis and myectomy, ileoanal anastomosis and myectomy with ileoileal valve, and ileoanal anastomosis with duplicated (J) ileal reservoir. The ratio of anaerobes to aerobes was significantly less in stool from dogs which had undergone ileoanal anastomosis compared with each of the other three groups (P less than 0.01). The numbers of streptococci and clostridia both were significantly less in stool from dogs with ileoanal anastomosis alone than in any other group. The concentrations of fecal acetic and propionic acids were significantly less in dogs with ileoanal anastomosis alone than in any other group (P less than 0.05), but there were no significant differences in the concentrations of fecal butyric or valeric acids. The severity of mucosal inflammation and degree of villous atrophy were more marked in the ileum of J reservoirs (P less than 0.01), and the percentage of stool retained after defecation was greater (P less than 0.05) in dogs with J reservoirs than in any other group. Therefore, the use of myectomy resulted in significant changes in the ecology of the distal ileum although changes typical of pouchitis were seen only in dogs with J reservoirs.

Comparison of triplicated (S) and quadruplicated (W) pelvic ileal reservoirs. Studies on manovolumetry, fecal bacteriology, fecal volatile fatty acids, mucosal morphology, and functional results.

Capacity and compliance, efficiency of evacuation, fecal bacteriology, fecal volatile fatty acids, mucosal morphology, and functional outcome were studied in 20 patients with triplicated (S) and 20 patients with quadruplicated (W) reservoirs after ileal pouch-anal anastomosis. Compared with patients with S reservoirs, patients with W reservoirs were found to have greater efficiency of evacuation of radiolabeled synthetic stool [97% (91%-98%) vs. 74% (62%-89%); P less than 0.05], and their reservoirs were more capacious [350 mL (320-400 mL) vs. 228 mL (175-290 mL); P less than 0.01] and compliant [16.0 mL/cm H2O (13.8-19.0 mL/cm H2O) vs. 12.3 mL/cm H2O (7.4-14.6 mL/cm H2O); P less than 0.01]. Effluent from S reservoirs contained significantly greater numbers of bacteroides (P less than 0.05) and concentrations of acetic and propionic acids (P less than 0.05) than effluent from W reservoirs. The degree of mucosal inflammation and villous atrophy in each design of reservoir was not significantly different. The ratio of anaerobes to aerobes in pouch effluent was significantly correlated with the degree of mucosal inflammation (rs = 0.433; P = 0.035). Fecal volatile fatty acids were significantly correlated with the percentage of stool retained after defecation and degree of mucosal inflammation. The frequency of bowel action was significantly less in patients with W reservoirs than in patients with S reservoirs [3.5/day (3-4/day) vs. 6.0/day (4-7/day); P less than 0.01]. The results indicate marked differences between these two ileal reservoir designs.

Quantitative changes in faecal microflora preceding necrotising enterocolitis in premature neonates.

Quantitative studies of faecal bacterial flora were carried out during the week preceding the clinical onset of 12 episodes of neonatal necrotising enterocolitis. There were considerable quantitative changes in the faecal flora preceding the clinical onset of both definite and possible episodes of necrotising enterocolitis. There was a decline in the numbers of some species from up to 72 hours before the clinical onset of the disease. Enterobacteriaceae were isolated from samples collected during the 48 hours preceding the clinical onset of all four definite episodes of necrotising enterocolitis. These were 'new' isolates in two episodes, and considerably increased numbers in another. The changes that we found are probably the result of changes in intraluminal conditions that precede the clinical onset of necrotising enterocolitis.

Synthesis of quaternary amine ether lipids and evaluation of neoplastic cell growth inhibitory properties.

Novel quaternary amine ether lipids have been synthesized and tested for inhibition of neoplastic cell proliferation with the HL-60 promyelocytic leukemia cell line. These compounds contain a positively charged quaternary amine functional group attached either directly to the glycerol backbone or at the end of an alkoxy chain. The biological testing has identified several analogues with activity equivalent to or greater than that exhibited by the reference compound in this assay, ET-18-OMe (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine). Among the most active analogues are compounds 11, [N,N,N-triethyl-3-(hexadecyloxy)-2-ethoxy-1-propylammonium bromide] and 22 [N-[4-[3-(hexadecyloxy)-2-ethoxypropoxy]-1-butyl]pyridinium bromide], which are approximately 3 times as active as the reference standard.