Is Cutibacterium (previously Propionibacterium) acnes a potential pathogenic factor in the aetiology of the skin disease progressive macular hypomelanosis?

Progressive macular hypomelanosis (PMH) is a skin condition that normally causes symmetrically distributed hypopigmented macules on the front and back of the trunk, but rarely the face. To date, the pathophysiology of the condition is not well understood, but a role for the anaerobic skin bacterium Cutibacterium (previously Propionibacterium) acnes in the development of the disease has been proposed due to its sole presence within lesional, but not normal peri-lesional, skin. The success of antimicrobials in the treatment of PMH also provides circumstantial evidence that this association may be causal, although this is still to be proven. More recent culture and metagenomic typing studies indicate that strains of C. acnes subsp. elongatum (type III) may be important in the aetiology of the condition, which would help to explain why PMH does not normally affect the face since such strains are rarely present there, and why no association between this condition and acne vulgaris is found; acne appears to primarily involve type IA1 strains from C. acnes subsp. acnes (type I). In this review, we summarize current knowledge on the relationship between C. acnes and PMH, and re-examine previous challenges to the view that the bacterium plays a role in the condition against the backdrop of newly emerged data.

Quantifying multiple sclerosis pathology in post mortem spinal cord using MRI.

Multiple sclerosis (MS) is a common inflammatory, demyelinating and degenerative disease of the central nervous system. The majority of people with MS present with symptoms due to spinal cord damage, and in more advanced MS a clinical syndrome resembling that of progressive myelopathy is not uncommon. Significant efforts have been undertaken to predict MS-related disability based on short-term observations, for example, the spinal cord cross-sectional area measured using MRI. The histo-pathological correlates of spinal cord MRI changes in MS are incompletely understood, however a surge of interest in tissue microstructure has recently led to new approaches to improve the precision with which MRI indices relate to underlying tissue features, such as myelin content, neurite density and orientation, among others. Quantitative MRI techniques including T1 and T2, magnetisation transfer (MT) and a number of diffusion-derived indices have all been successfully applied to post mortem MS spinal cord. Combining advanced quantification of histological features with quantitative - particularly diffusion-based - MRI techniques provide a new platform for high-quality MR/pathology data generation. To more accurately quantify grey matter pathology in the MS spinal cord, a key driver of physical disability in advanced MS, remains an important challenge of microstructural imaging.

Intra- and inter-observer reproducibility of CINtec® PLUS in ThinPrep® cytology preparations.

BACKGROUND: This study evaluated the intra- and inter-observer reproducibility of the dual-stain biomarker, CINtec® PLUS cytology in ThinPrep® specimens, for improved specificity in the detection of cervical disease in women testing human papillomavirus (HPV) positive. METHODS: A total of 972 cases of HPV-positive women from a triage and primary HPV screening population were selected from an ongoing study evaluating the clinical performance of CINtec® PLUS cytology. For reproducibility analyses, three cytotechnologists rescreened sets of slides which they had previously reported themselves and which were previously reported by each of the other cytotechnologists. The original results of slides previously screened by each of the three cytotechnologists were also compared with the results of an expert reference evaluator. RESULTS: Intra- and inter-observer agreement for paired evaluations between reviewers ranged from 82.8% to 94.9% (kappa 0.65-0.91) and 89.2% to 93% (kappa 0.83-0.88), respectively. Reproducibility analyses between the cytotechnologists and the reference evaluator revealed agreements ranging from 95.5% to 98% (kappa 0.89-0.96). CONCLUSION: Evaluation of the dual-stain biomarker showed a high level of agreement across all evaluators suggesting that CINtec® PLUS cytology will perform well in the hands of cytotechnologists and pathologist reviewers and could be introduced into cellular pathology laboratories that employ ThinPrep® LBC with a minimum effort.

HPV16 and HPV18 genotyping triage in young women with borderline cytology or mild dyskaryosis: effect of age on genotype-specific risk of high-grade CIN.

OBJECTIVE: Human papillomavirus (HPV) triage of borderline cytology or mild dyskaryosis is limited by the higher prevalence of HPV in women with these findings relative to those with high-grade cervical intraepithelial neoplasia (≥CIN2). This is particularly relevant in young women in whom HPV prevalence is discernible. In a previous analysis of HPV triage and colposcopy outcomes in Northern Ireland, we revealed a substantial amount of prevalent high-grade disease in women below 30 years of age. We explored the role of genotyping for HPV16/HPV18 in this population by assessing the risk of high-grade lesions associated with these genotypes and the effect of age on type-specific risk. METHODS: Of the 866 women eligible for HPV triage, those who tested positive for HPV were referred to colposcopy. The relative risk of ≥CIN2 for HPV16, HPV18 and non-HPV16/18 high-risk genotype positivity was determined for cobas(®) HPV Test-positive results. RESULTS: The relative risk of high-grade CIN was significantly greater in women infected with HPV16 and/or HPV18 compared with non-HPV16/18 infections, regardless of age (2.23 and 0.45, respectively). In women under 30 years of age, HPV16-associated risk of ≥CIN2 was significantly greater than that of HPV18 and the non-HPV16/18 genotypes (1.74 versus 1.03 and 0.58, respectively). In women aged ≥30 years, HPV18 infection presented the greatest risk of ≥CIN2 (3.03). The relative risk of ≥CIN2 associated with non-HPV16/18 genotypes was lower (range, 0.32-0.58) for both age groups. CONCLUSION: This analysis demonstrates the value of genotyping for HPV16/HPV18 and age stratification to improve the specificity of HPV triage and to tailor management relative to the risk of high-grade CIN and cancer.

An increased incidence of Propionibacterium acnes biofilms in acne vulgaris: a case-control study.

BACKGROUND: Acne vulgaris is a disorder of the sebaceous follicles. Propionibacterium acnes can be involved in inflammatory acne. OBJECTIVES: This case-control study aimed at investigating the occurrence and localization of P. acnes in facial biopsies in acne and to characterize the P. acnes phylotype in skin compartments. METHODS: Specific monoclonal and polyclonal antibodies were applied to skin biopsies of 38 patients with acne and matching controls to localize and characterize P. acnes and to determine expression of co-haemolysin CAMP factor, a putative virulence determinant. RESULTS: Follicular P. acnes was demonstrated in 18 (47%) samples from patients with acne and eight (21%) control samples [odds ratio (OR) 3·37, 95% confidence interval (CI) 1·23-9·23; P = 0·017]. In 14 (37%) samples from patients with acne, P. acnes was visualized in large macrocolonies/biofilms in sebaceous follicles compared with only five (13%) control samples (OR 3·85, 95% CI 1·22-12·14; P = 0·021). Macrocolonies/biofilms consisting of mixed P. acnes phylotypes expressing CAMP1 were detected in both case and control samples. Only four samples tested positive for the presence of Staphylococcus spp. and fungi were not observed. CONCLUSIONS: We have for the first time visualized different P. acnes phylotypes in macrocolonies/biofilms in sebaceous follicles of skin biopsies. Our results support the hypothesis that P. acnes can play a role in the pathogenesis of acne as acne samples showed a higher prevalence of follicular P. acnes colonization, both in terms of follicles containing P. acnes and the greater numbers of bacteria in macrocolonies/biofilms than in control samples.

Point-source outbreak of coccidioidomycosis in construction workers.

Coccidioidomycosis results from inhaling spores of the fungus Coccidioides spp. in soil or airborne dust in endemic areas. We investigated an outbreak of coccidioidomycosis in a 12-person civilian construction crew that excavated soil during an underground pipe installation on Camp Roberts Military Base, California in October 2007. Ten (83.3%) workers developed symptoms of coccidioidomycosis; eight (66.7%) had serologically confirmed disease, seven had abnormal chest radiographs, and one developed disseminated infection; none used respiratory protection. A diagnosis of coccidioidomycosis in an eleventh worker followed his exposure to the outbreak site in 2008. Although episodic clusters of infections have occurred at Camp Roberts, the general area is not associated with the high disease rates found in California's San Joaquin Valley. Measures to minimize exposure to airborne spores during soil-disrupting activities should be taken before work begins in any coccidioides-endemic area, including regions with only historic evidence of disease activity.

New Zealand Drivers Study: a follow-up study of newly licensed drivers.

BACKGROUND: Despite significant improvement since graduated licensing was introduced, traffic-related injury remains the leading cause of death and hospitalisation among young New Zealanders. Most research to date has used routinely collected crash data but has been limited in that these databases do not, and realistically cannot, include the level of detail required to ensure that learner driver policy and programmes are based on sound scientific evidence applicable to young drivers in the current New Zealand context. OBJECTIVES: To examine the driving-related experiences of newly licensed drivers to identify factors associated with increased or decreased risk of negative traffic outcomes. DESIGN: Multistage prospective cohort study. SETTING: New Zealand. PARTICIPANTS: Newly licensed drivers. EXPOSURES: background demographic details, pre-licence driving, previous crashes, driving intentions, motivations for driving and licensing, sensation seeking, aggression, impulsivity, quality and quantity of driving experience, driving supervision, driving behaviour, alcohol and other drug use, compliance with New Zealand's graduated driver licensing scheme, driver training/education, cell phone use, and sleep. OUTCOMES: crash, conviction, infringements, risky driving. EXPOSURES: participants and their parents. Outcomes: participants and official records. BIAS: On the basis of a pilot study, participation and attrition bias are likely to be minimal. A comparison of baseline data for those followed and those not followed will be undertaken. Information bias will be minimised by standardised questionnaires. Information on potential confounders is to be collected and controlled for in analyses. STUDY SIZE: 5000 (including 1500 Maori). STATISTICAL METHODS: Survival analysis, logistic or Poisson regression, generalised estimating equations.

Biofilm formation by bacteria isolated from retrieved failed prosthetic hip implants in an in vitro model of hip arthroplasty antibiotic prophylaxis.

Bacterial infection primarily with Staphylococcus spp. and Propionibacterium acnes remains a significant complication following total hip replacement. In this in vitro study, we investigated the efficacy of gentamicin loading of bone cement and pre- and postoperative administration of cefuroxime in the prevention of biofilm formation by clinical isolates. High and low initial inocula, representative of the number of bacteria that may be present at the operative site as a result of overt infection and skin contamination, respectively, were used. When a high initial inoculum was used, gentamicin loading of the cement did not prevent biofilm formation by the 10 Staphylococcus spp. and the 10 P. acnes isolates tested. Similarly, the use of cefuroxime in the fluid phase with gentamicin-loaded cement did not prevent biofilm formation by four Staphylococcus spp. and four P. acnes isolates tested. However, when a low bacterial inoculum was used, a combination of both gentamicin-loaded cement and cefuroxime prevented biofilm formation by these eight isolates. Our results indicate that this antibiotic combination may protect against infection after intra-operative challenge with bacteria present in low numbers as a result of contamination from the skin but would not protect against bacteria present in high numbers as a result of overt infection of an existing implant.

Antisepsis of the skin before spinal surgery with povidone iodine-alcohol followed by chlorhexidine gluconate-alcohol versus povidone iodine-alcohol applied twice for the prevention of contamination of the wound by bacteria: a randomised controlled trial.

AIMS: The aim of this study was to determine whether the sequential application of povidone iodine-alcohol (PVI) followed by chlorhexidine gluconate-alcohol (CHG) would reduce surgical wound contamination to a greater extent than PVI applied twice in patients undergoing spinal surgery. PATIENTS AND METHODS: A single-centre, interventional, two arm, parallel group randomised controlled trial was undertaken, involving 407 patients who underwent elective spinal surgery. For 203 patients, the skin was disinfected before surgery using PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, povidone iodine; Videne Alcoholic Tincture) twice, and for 204 patients using PVI once followed by CHG (2% [w/v] chlorhexidine gluconate in 70% [v/v] isopropyl alcohol; Chloraprep with tint). The primary outcome measure was contamination of the wound determined by aerobic and anaerobic bacterial growth from samples taken after disinfection. RESULTS: The detection of viable bacteria in any one of the samples taken after disinfection (culture-positive) was significantly lower in the group treated with both PVI and CHG than in the group treated with PVI alone (59 (29.1%) versus 85 (41.7%), p = 0.009; odds ratio 0.574; 95% confidence interval, 0.380 to 0.866). CONCLUSIONS: Antisepsis of the skin with the sequential application of PVI and CHG more effectively reduces the contamination of a surgical wound than PVI alone. Cite this article: Bone Joint J 2017;99-B:1354-65.

Dual targeting of EGFR and ERBB2 pathways produces a synergistic effect on cancer cell proliferation and migration in vitro.

Members of the epidermal growth factor receptor (EGFR/ERBB) gene family are frequently dysregulated in a range of human cancers, and therapeutics targeting these proteins are in clinical use. We hypothesized that similar pathways are involved in feline and canine tumours and that the same drugs may be of clinical use in veterinary patients. We investigated EGFR and ERBB2 targeting using a panel of feline and canine cell lines. EGFR and ERBB2 were targeted with siRNAs or tyrosine kinase inhibitors (TKIs) and their effect on cellular proliferation, colony formation and migration was investigated in vitro. Here we report that EGFR and ERBB2 combined siRNA targeting produced synergistic effects in feline and canine cell lines similar to that reported in human cell lines. We conclude that dual EGFR and ERBB2 targeting using TKIs should be further evaluated as a potential new therapeutic strategy in feline head and neck and mammary tumours and canine mammary tumours.

Mechanisms of inducible nitric oxide synthase-mediated vascular dysfunction.

OBJECTIVE: Inducible nitric oxide synthase (iNOS) is expressed in arteries during inflammation and may contribute to vascular dysfunction. Effects of gene transfer of iNOS to carotid arteries were examined in vitro in the absence of systemic inflammation to allow examination of mechanisms by which iNOS impairs contraction and relaxation. METHODS AND RESULTS: After gene transfer of iNOS with an adenovirus (AdiNOS), constrictor responses to phenylephrine (PE) and U46619 were impaired. After AdiNOS, inhibition of soluble guanylate cyclase (sGC) with 1H-[1,2,4]oxadiazolo-[4,3,2]quinoxalin-1-one (ODQ) reduced the EC50 for PE from 4.33+/-0.78 micromol/L to 1.15+/-0.43 micromol/L (mean+/-SEM). These results imply that iNOS impairs contraction by activation of the NO/cGMP pathway. Relaxation to acetylcholine (ACh) also was impaired after AdiNOS. Sepiapterin (300 micromol/L), the precursor for tetrahydrobiopterin (BH4), improved relaxation to Ach. Because BH4 is an essential cofactor for production of NO by both iNOS and endothelial nitric oxide synthase (eNOS), these results suggest that iNOS may reduce production of NO by eNOS by limiting availability of BH4. Next, we examined effects of expression of iNOS in endothelium and adventitia. Selective expression of iNOS in endothelium, but not adventitia, impaired contraction to phenylephrine and relaxation to acetylcholine. CONCLUSIONS: We conclude that: (1) iNOS may impair contraction in part by activation of sGC; (2) iNOS impairs relaxation, at least in part, by limiting availability of BH4; and (3) expression of iNOS in endothelium may be a more important mediator of vascular dysfunction than expression of iNOS in adventitia.

Treatment as diagnosis and diagnosis as treatment: empirical management of presumptive tuberculosis in India.

BACKGROUND: Mismanagement of TB is a concern in the Indian private sector, and empirical management might be a key contributor. OBJECTIVE: To understand factors associated with empirical diagnosis and treatment of presumed TB in India's private sector and examine their effects on TB care. DESIGN: In this ethnographic study, 110 private practitioners of varying qualification who interacted with TB patients (90 in Mumbai and 20 in Patna) were interviewed, and a subset was observed while providing clinical care. Interviews and observations were analysed for indicators of empirical diagnosis and treatment. RESULTS: All non-specialist practitioners began antibiotic treatment, especially quinolones, for persistent cough before prescribing a test. Several factors contribute to empirical management. These include a common practice use of medications as diagnostic tools, a desire to provide rapid symptom relief to patients, a desire to manage illness costs effectively, uncertainty about the presentation of TB, the effects of broad spectrum antibiotics on TB symptomology, and uncertainty about the accuracy of available TB tests. CONCLUSION: Empiricism in general and in TB care is widespread in the urban private sector in India. Ethnography might offer useful insights for addressing this in public-private mix models.

Gastrointestinal transit in the common brushtail possum measured by gamma scintigraphy.

This paper reports an example of the application of pharmaceutical technology to wildlife management, specifically the design of an oral delivery system for the common brushtail possum in New Zealand. Designing an oral delivery system requires a knowledge of the time taken for particulates to reach target sites within the gastrointestinal tract (GIT). The transit time for fluid and indigestible particles of two different size ranges was determined in the common brushtail possum (Trichosurus vulpecula). Technetium-labelled (99mTc) anion exchange resin particles (75-125 or 500-700 microm diameter) or solution (99mTc-labelled diethylenetriamine pentaacetic acid, 99mTc-DTPA) was administered orally. At predetermined times after dosing (3, 6, 12, 24 or 32 h), the distribution of radioactivity throughout excised gastrointestinal tracts was determined by gamma scintigraphy. The transit profile was similar for the three formulations investigated. Unlike other closely related hindgut fermenting marsupials, there was no evidence to support the presence of a colonic separating mechanism in the common brushtail possum. Gastrointestinal transit was independent of body mass, gender and time of day that the dose is given. To target the hindgut for oral delivery of protein and peptide biocontrol agents, the formulation would need to protect the bioactive for approximately 12 h prior to release.

In vivo inhibition of glucocorticoid-inducible gene expression by dimethylnitrosamine in rat liver.

Sprague-Dawley rats were pretreated with a single i.p. injection of either 2.25 mL/kg of phosphate-buffered saline (PBS) or 22.5 mg/kg of dimethylnitrosamine (DMN) followed 2 hr later by a single i.p. injection of either 1.35 mg/kg of dexamethasone (DEX) or the vehicle, a 50% ethanol solution, both delivered in a volume of 3 mL/kg. RNA levels of the hormone-inducible, specialized liver function genes, tyrosine aminotransferase (TAT) and glutamine synthetase (GS), were monitored 4, 5, 6, 7, 8, and 10 hr after the DEX injection. Maximal induction of both the TAT (26-fold) and GS (6-fold) RNAs occurred 6 hr after DEX administration in PBS-pretreated animals. Pretreatment with DMN caused at least a 42% inhibition of DEX-induced RNA accumulation at every time point examined, with greater than 90% inhibition occurring when the genes were maximally induced at 6 hr. This inhibition was not due to any alterations of the glucocorticoid receptors as DMN had no effect on the binding affinity or amounts of glucocorticoid receptors present in rat hepatic cytosols. These results suggest that chemical carcinogens such as DMN may affect normal gene function in vivo by inhibiting the cellular response to hormone receptors mediating differentiation-associated, specialized cell functions.

Effect of metoclopramide, bethanechol and the cholecystokinin receptor antagonist, L-364,718, on gastric emptying in the rat.

The prokinetic effects of metoclopramide, bethanechol and L-364,718 on a semisolid meal and solid pellet gastric emptying were evaluated and compared. Each compound increased the rate of meal emptying as measured 90 min post-dose. L-364,718, a non-peptide CCK antagonist, was the most potent of these three agents with statistically significant activity observed at 0.03, 0.1 and 0.3 mg/kg p.o. Only metoclopramide significantly enhanced pellet emptying in a dose-dependent manner (3-30 mg/kg p.o.). The effects of each test agent and the potential physiologic role of cholecystokinin in regulating gastric emptying are discussed.

What are the conditions for exponential time-cubed echo decays?

Diffusion of precessing spins through a constant field gradient is well-known to produce two distinctive features: an exp(-bt(3)) decay of the echo amplitude in response to two pulses and a much slower decay of the Carr-Purcell echo train. These features will appear whenever the spin frequency is described by a continuous random-walk. The present work shows that this may also occur in the presence of motions with long correlation times tau(c)-continuous Gaussian frequency noise with an exponential autocorrelation has the correct properties over time durations smaller than tau(c). Thus, time-cubed echo decays will occur in situations other than physical diffusion. The decay rate of the Carr-Purcell echo train is shown to vary with the pulse spacing tau whenever the correlation time tau(c) is long; the slower Carr-Purcell decay compared to the two-pulse echo decay is not unique to diffusion. Simulations are presented that display time-cubed decays. The simulations confirm two important criteria: the echo time must be less than tau(c) and the frequency noise must consist of nearly continuous variations, as opposed to step-like changes. These criteria define the range of physical parameters for which time-cubed decays will be observable.

Clinical outcome of Burkholderia cepacia complex infection in cystic fibrosis adults.

BACKGROUND: The Burkholderia cepacia complex (BCC) is one of the most important groups of organisms infecting cystic fibrosis (CF) patients. The aim of the study was to examine how infection with BCC affects clinical outcome. METHODS: Nineteen CF adults infected with BCC and 19 controls infected with Pseudomonas aeruginosa were studied over a 4-year period. The best forced expiratory volume in 1 s (FEV(1)) and body mass index (BMI) for each year were recorded and annual rate of decline calculated. RESULTS: The BCC infected group displayed a significantly greater reduction of FEV(1) and BMI compared to the P. aeruginosa infected group (p=0.001 and p=0.009, respectively). Sixteen patients infected with a single Burkholderia cenocepacia strain had a significantly greater rate of FEV(1) decline compared to those infected with Burkholderia multivorans (n=3) or P. aeruginosa (p=0.01 and p<0.0001, respectively). The rate of BMI decline was significantly greater in patients infected with B. cenocepacia compared to those with P. aeruginosa (p=0.007), but not significantly different in those with B. multivorans (p=0.29). CONCLUSION: BCC infection is associated with an accelerated decline in pulmonary function and BMI. Infection with a single B. cenocepacia strain was associated with a more rapid decline in lung function than those infected with either B. multivorans or P. aeruginosa.

Nutrition knowledge and attitudes of cardiac patients.

OBJECTIVE: Despite the importance of dietary factors in treating and preventing heart disease, relatively little work has explored how well cardiac patients understand the nutrition information they are given. This study was designed to assess the nutrition knowledge and attitudes of cardiac patients. DESIGN: An onsite survey was administered to patients who were waiting to see their cardiologists. The survey focused on patients' medical history, attitudes toward nutrition, and knowledge of "heart-healthy" dietary information. SETTING: Cardiology practices in New England, Southern California, and the Midwest. SUBJECTS: A total of 606 patients completed the survey (roughly 74% of those approached). RESULTS: Most patients rated dietary factors as extremely important in treating and preventing heart disease, and 67.0% of those who had experienced a heart attack reported believing that diet had played a contributing role. Nonetheless, nutrition knowledge was marginal. Despite the fact that 92.4% of patients reported receiving dietary literature, overall accuracy rates on responses to nutrition questions did not exceed chance levels. Only 30.5% of the patients who were given dietary literature reported understanding it completely. CONCLUSIONS: Nutrition counseling should receive higher priority, both in medical training and in patient care, and cardiac patients should be referred to dietitians on a more routine basis. Physicians should not assume that patients who are given dietary information understand the materials they receive.

Increased metallothionein gene expression in 5-aza-2'-deoxycytidine-induced resistance to cadmium cytotoxicity.

The pyrimidine analog, 5-azacytidine (AZA-CR), has been shown to increase the expression of the metallothionein (MT) gene and to induce tolerance to cadmium toxicity. Since incorporation into DNA of AZA-CR appears to be required for this effect, the deoxynucleoside of AZA-CR should also be effective. Therefore, this study was undertaken to assess the effect of 5-aza-2'-deoxycytidine (AZA-CdR) pretreatment on cadmium-induced cytotoxicity and MT expression in cultured cells. TRL 1215 cells in log phase of growth were exposed to AZA-CdR (0.4, 0.8, 4.0, 8.0 microM) followed 48 h later by the addition of cadmium (10 microM). MT concentrations were measured 24 h after the addition of cadmium. AZA-CdR alone caused modest, dose-related increases in MT levels (2.3-fold maximum), while cadmium alone resulted in a 9.5-fold increase. Pretreatment with AZA-CdR in combination with cadmium caused a 19--24-fold increase in cellular MT at all doses of AZA-CdR. Addition of the DNA synthesis inhibitor, hydroxyurea (HU), to the incubation medium during AZA-CdR exposure prevented the enhancing effect of the analog on cadmium induction of MT accumulation. Time course studies revealed that AZA-CdR pretreatment reduced the time required for cadmium to induce MT levels from 4--8 h to 0--2 h. AZA-CdR pretreated cells placed in suspension with cadmium (125 microM) showed a marked reduction in cadmium-induced cytotoxicity as reflected by reduced glutamic-oxaloacetic transaminase (GOT) loss. Uptake studies showed that AZA-CdR pretreatment had no effect on cadmium transport during the initial phases of exposure, indicating that an alteration in the toxicokinetics of the metal did not account for the reduction in toxicity. AZA-CdR did, however, cause hypomethylation of the MT-I gene. These results suggest that AZA-CdR pretreatment induces tolerance to cadmium toxicity by increasing the genetic expression of MT possibly through hypomethylation of the MT gene.

Simultaneous multicomponent drug determinations with a vidicon spectrometer.

A vidicon spectrometer, useful for absorption spectrophotometry over the 210-800-nm spectral region and capable of scanning a portion of this region at repetition rates of 250 scans/sec, was applied for the simultaneous determination of multicomponent drug formulations without a separation. Results are reported for two drug preparations containing two and four active components. The average of ratios of determined to expected values for the six active components contained in both formulations was 99.2% based on the specified tablet contents. Relative standard errors for the analyses were less than 3%. Other potential applications of the vidicon spectrometer are discussed briefly.