Oxidative stress and neopterin abnormalities in schizophrenia: A longitudinal study

Oxidative stress abnormalities have been proposed to explain the pathogenesis of schizophrenia. The present study examined neopterin and oxidative stress abnormalities in schizophrenia patients before and after treatment. Serum neopterin, total anti-oxidants, nitrites and thiols in antipsychotic-naïve schizophrenia patients (n = 45) were assessed at baseline before treatment in comparison with healthy controls (n = 43). The schizophrenia patients on treatment were followed up for 3 months and these parameters were reassessed (n = 32). In comparison to healthy controls, schizophrenia patients had significantly higher levels of neopterin and nitrites and significantly lower levels of anti-oxidants before treatment. During follow-up assessments in schizophrenia patients after treatment with antipsychotics, there was a significant decrease in the neopterin levels and significant increase in anti-oxidant levels. Our study observations support increased oxidative stress in schizophrenia that improves with antipsychotic treatment.     

Development of quantitative structure-activity relationship (QSAR) models to predict the carcinogenic potency of chemicals: I. Alternative toxicity measures as an estimator of carcinogenic potency

Determining the carcinogenicity and carcinogenic potency of new chemicals is both a labor-intensive and time-consuming process. In order to expedite the screening process, there is a need to identify alternative toxicity measures that may be used as surrogates for carcinogenic potency. Alternative toxicity measures for carcinogenic potency currently being used in the literature include lethal dose (dose that kills 50% of a study population [LD₅₀]), lowest-observed-adverse-effect-level (LOAEL) and maximum tolerated dose (MTD). The purpose of this study was to investigate the correlation between tumor dose (TD₅₀) and three alternative toxicity measures as an estimator of carcinogenic potency. A second aim of this study was to develop a Classification and Regression Tree (CART) between TD₅₀ and estimated/experimental predictor variables to predict the carcinogenic potency of new chemicals. Rat TD₅₀s of 590 structurally diverse chemicals were obtained from the Cancer Potency Database, and the three alternative toxicity measures considered in this study were estimated using TOPKAT^®, a toxicity estimation software. Though poor correlations were obtained between carcinogenic potency and the three alternative toxicity (both experimental and TOPKAT) measures for the CPDB chemicals, a CART developed using experimental data with no missing values as predictor variables provided reasonable estimates of TD₅₀ for nine chemicals that were part of an external validation set. However, if experimental values for the three alternative measures, mutagenicity and logP are not available in the literature, then either the CART developed using missing experimental values or estimated values may be used for making a prediction.     

Less-Frequent Fusarium Species of Clinical Interest: Correlation between Morphological and Molecular Identification and Antifungal Susceptibility

Forty-eight Fusarium isolates morphologically identified as belonging to seven species of clinical interest (i.e., Fusarium chlamydosporum, Fusarium dimerum, Fusarium incarnatum, Fusarium napiforme, Fusarium nygamai, Fusarium proliferatum, and Fusarium sacchari) were characterized molecularly by the analysis of the sequences of the TUB region of the β-tubulin gene. F. chlamydosporum and F. dimerum were the most genetically heterogeneous species. A high degree of correlation between the morphological and molecular identification was shown among the isolates studied. A table with the key morphological features for the identification of these Fusarium species is provided. The antifungal susceptibilities of the Fusarium isolates to 11 antifungal drugs were tested; terbinafine was the most active drug against all the species tested with the exception of F. incarnatum, for which amphotericin B was the most active.The most frequent species causing fusariosis are Fusarium solani, Fusarium oxysporum, and Fusarium verticillioides (1, 16, 47), but several other species are also found to cause human infections, although less frequently. Some of these species are Fusarium chlamydosporum, Fusarium dimerum, Fusarium incarnatum, and the following other species that are included into the Gibberella fujikuroi species complex: Fusarium napiforme, Fusarium nygamai, Fusarium proliferatum, and Fusarium sacchari (30, 31). These species have been associated with different types of infection, in particular with keratomycoses and other ocular infections (10) and with disseminated infections in immunocompromised patients (2, 6, 17, 20, 23, 24, 26, 39, 41, 43, 44). The real incidence of these species is unknown since they are poorly known and laboratorians and clinical microbiologists are not generally aware of their possible presence in human infections.Since the species of Fusarium are generally resistant to all the available antifungal drugs (40), it could be considered that speciation of Fusarium is necessary only for epidemiological purposes. However, some in vitro data concerning particular species seem to be very promising and deserve to be investigated clinically. For instance, F. verticillioides isolates were susceptible to posaconazole and terbinafine and Fusarium thapsinum isolates to terbinafine (4). The identification of fusaria to the species level is not easy, and in numerous clinical cases the etiological agent is reported as being a Fusarium sp. However, several recent studies have demonstrated the usefulness of molecular methods for the identification of those Fusarium species that are difficult to distinguish morphologically (1, 4, 47). In recent years, the in vitro antifungal susceptibilities of the most frequent species of Fusarium have been evaluated (1, 3, 4, 40, 47), but only a few isolates of the less-common species have been studied. The objectives of our study were (i) to evaluate the correlation between the morphological and the molecular identification of less-frequent Fusarium species isolates received by our laboratory and (ii) to determine the antifungal susceptibilities of isolates representative of those less-common Fusarium species of clinical interest identified molecularly.     

Haplotype analysis of HLA‐A, ‐B antigens and ‐DRB1 alleles in south Indian HIV‐1‐infected patients with and without pulmonary tuberculosis

We have shown earlier the association of human leucocyte antigen (HLA)‐A11 with resistance and HLA‐B40 and ‐DR2 with susceptibility to HIV and HIV‐TB. In the present study, we have attempted to find out the HLA‐DR2 subtypes and the possible HLA‐A/‐B/‐DRB1 haplotype combinations that are associated with susceptibility or resistance to HIV and HIV with pulmonary tuberculosis (HIV+PTB+). HLA‐DR2 subtyping was carried out by polymerase chain reaction‐based sequence‐specific oligonucleotide probe method. Overrepresentation of HLA‐DRB1*1501 in HIV‐positive PTB‐negative (HIV+PTB–) patients (P = 0.004, P_c = 0.06) and ‐DRB1*1502 in HIV‐positive PTB‐positive (HIV+PTB+) patients (P = 0.019) was observed as compared to healthy controls. Haplotype analysis revealed an increased frequency of HLA‐A2‐DRB1*1501 haplotype in HIV+PTB– patients (P = 0.008) and HLA‐A2‐DRB1*1502 among HIV+PTB+ patients (P = 0.01) compared to healthy controls. The haplotypes B40‐DRB1*1501 and B40‐DRB1*04 were found to be moderately increased in HIV+PTB– and HIV+PTB+ patients (P < 0.05). The study suggests that HLA‐A2‐DRB1*1501 haplotype may be associated with HIV infection while HLA‐A2‐DRB1*1502 haplotype might be associated with susceptibility to PTB in HIV patients. Moreover, HLA‐B40‐DRB1*1501 and HLA‐B40‐DRB1*04 haplotypes may be associated with susceptibility to HIV infection and to PTB in HIV patients.     

Increasing nevirapine dose can overcome reduced bioavailability due to rifampicin coadministration

We studied the effect of rifampicin on steady-state pharmacokinetics of nevirapine and the impact of increasing the dose of nevirapine on its peak (Cmax) and trough (Cmin) levels in 13 HIV-infected patients on regular antiretroviral treatment with nevirapine-containing regimens (200 mg twice daily). A baseline pharmacokinetic study was conducted and repeated after 1 week of daily rifampicin (450/600 mg). The study was repeated in 7 of 8 patients who had subtherapeutic Cmin nevirapine levels after increasing nevirapine dose to 300 mg twice daily. Liver function was monitored. Rifampicin caused significant reductions in Cmax (42%), Cmin (53%), and exposure (46%) of nevirapine (P <.01). The Cmin of nevirapine fell below the therapeutic range of 3 microg/ml in 8 of 13 patients. An increase of nevirapine to 300 mg twice daily raised Cmin to therapeutic range in all 7 patients without exceeding the toxic level of 12 microg/mL. There were no clinical or laboratory adverse events. Our findings suggest that decreased bioavailability of nevirapine because of rifampicin coadministration could be overcome by increasing the dose of nevirapine from 200 to 300 mg twice daily without short-term adverse events. Further studies to evaluate the long-term safety of higher dose of nevirapine are required.     

Blood storage at 4 degrees C-factors involved in DNA yield and quality

BACKGROUND: Whole blood provides one of the most common sources of both high-quality DNA and high-quantity DNA for molecular biological purposes. Typically, blood storage at 4 degrees C is short term, which ranges from a few days to a few weeks. However, long-term storage usually involves blood being frozen, with a resultant loss in DNA yield. The authors examined the effects of long-term storage at 4 degrees C. METHODS: Duplicate blood samples were collected from 301 participants (aged 20-98 years) enrolled as part of ongoing studies. Samples were stored at 4 degrees C for between 11 days and 922 days, and DNA was subsequently extracted using a phenol/chloroform procedure. RESULTS: A negative correlation of the number of storage days existed at 4 degrees C with DNA yield. The main determinant on DNA yield was the age of the participant in the study, with older persons having a lower DNA yield. CONCLUSIONS: Long-term storage of blood at 4 degrees C does have a detrimental effect on DNA yield, but this effect seemed less significant than the age of a person. The impact of age of a person or storage time has a minimal impact on DNA quality. Therefore, storage of blood at 4 degrees C offers an acceptable alternative to frozen storage.