Pathological pain has been subjected to intense research to shed light on the underlying mechanisms of key symptoms, such as allodynia and hyperalgesia. Toxicity of 38 aliphatic carboxylic acids was studied by using a quantitative structure–activity relationship (QSAR) method and the following molecular and topological properties: acidic dissociation constant, electrotopological states, molar refractivity, refraction index, log Kow, ELUMO, surface tension, and polarizability. DNA electrotransfer to muscle tissue yields long-term, high levels of gene expression; showing great promise for future gene therapy. We have previously demonstrated that high tumor tissue levels of TIMP-1 are associated with no or limited clinical benefit from chemotherapy with CMF and anthracyclines in metastatic breast cancer patients. In this selected cohort of high-risk patients, and in the subgroup of patients receiving no adjuvant therapy, TIMP-1 was not associated with prognosis. In the subgroup of patients receiving adjuvant chemotherapy we found an association between shorter survival after treatment in TIMP-1 high patients compared with TIMP-1 low patients, especially in patients receiving anthracycline-based therapy. This study aimed to investigate the effect of a novel kind of immune-stimulating complexes (ISCOMs) on human skin penetration of model compounds in vitro to evaluate their potential as a delivery system, ultimately for transcutaneous vaccination.
In an effort to develop a porcine model of Alzheimer’s disease we used handmade cloning to produce seven transgenic Gottingen minipigs.
Animal models have shown histamine to be released from the skin during the acute phase of a burn injury. The objectives of this trial were to study histamine release in human skin during the acute phase of a standardized thermal injury in healthy volunteers. Spectrofluorometric assay of histamine showed no histamine release in separate studies using 2-min samples over 20 min (n = 6) and 5–10-min samples over 120 min (n = 8).
Hepatic encephalopathy is a severe neuropathological condition arising secondary to liver failure. The Strong Heart Study is a longitudinal, cohort study of cardiovascular disease among American Indians. Our results confirm the effects of variant structural (B, C, and D) and promoter (H and Y) alleles that have been seen in other populations. New data is presented concerning the effects of known genetic variants on MBL levels in an American Indian population, as well as the relationship of MBL2 expression to clinical and environmental factors, including inflammatory markers. Aim: The aim of the present study was to determine the allelic and genotypic frequencies of NQO Hinf I polymorphisms in a Hindu population of Central India.
Settings and Design: Polymorphisms of NQO1 were determined in 311 unrelated Hindu individuals. Materials and Methods: Polymerase chain reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) analysis in peripheral blood DNA for NQO1 Hinf I polymorphism was used in 311 unrelated Hindu individuals. Results: The observed allelic frequency was 81% for C (wild) and 19% for T (mutant) in the total sample. Conclusions: The allelic frequency of "C" was higher than in other Asians (57%), but similar to Caucasians (81%). Phase I enzyme DT-diphorase [NAD (P) H: quinone oxidoreductase 1 (NQO1)] converts toxic benzoquinone into hydroquinone in an obligate two-electron reduction reaction and is a key enzyme in polycyclic hydrocarbon metabolism in humans. NQO1 is a key enzyme in carcinogen metabolism and its allelic frequency varies by ethnicity. The main focus has by and large concerned plasticity of spinal cord neurons and the primary afferent nerves relaying peripheral information to the spinal cord. Application of realistic molecular quantities that can express the toxicities of the molecules is the idea behind the choice of these topological and physicochemical descriptors.
Acidic dissociation constant, surface tension, log Kow, and the electrotopological state of the methyl group were selected as significant descriptors, using a backward elimination method on the top descriptors obtained from the genetic algorithm. We want to characterize the novel far-red fluorescent protein Katushka as a marker for gene expression using time domain fluorescence in vivo imaging. Here, we extend our investigations to the adjuvant setting studying outcome after adjuvant chemotherapy in premenopausal lymph node-positive patients. This suggests that high tumor tissue levels of TIMP-1 might be associated with reduced benefit from classical adjuvant chemotherapy.
The donor fibroblasts had been stably transfected with a plasmid cassette containing, as transgene, the cDNA of the neuronal variant of the human amyloid precursor protein gene with the Swedish mutation preceded by beta-globin sequences to induce splicing and a human PDGFbeta promoter fragment to drive transcription. The role of histamine during the early phase of thermal injuries in humans remains unclear.
Microdialysis fibers were inserted into the dermis in the lower leg in male healthy volunteers. The histamine values were at the limits of the quantification limit of the spectrofluorometric assay. The pathogenesis is not well understood; however, hyperammonemia is considered to be one causative factor. Persistent, subclinical infections and chronic inflammatory states are hypothesized to contribute to the pathogenesis of atherosclerosis.
A subset of individuals genotyped for the above mentioned case-control study were selected for analysis of circulating MBL levels by double sandwich ELISA method. In addition, MBL levels were found to be positively associated with male gender and hemoglobin A1c levels, but inversely related to triglyceride levels.
This enzyme has been associated with xenobiotic related diseases, such as cancer, therapeutic failure and abnormal effects of drugs.
All the subjects were the regular residents of the Vindhyan region, the heart land of India.
The variable frequency of NQO1 makes some populations more susceptible for getting cancerous disease due to the inability to detoxify the carcinogen by null allele. Persuasive evidence that quinone reductase type 1 (DT-diaphorase) protects cells against the toxicity of electrophiles and reactive forms of oxygen.

Lung cancer in Mexican-Americans and African-Americans is associated with the wild-type genotype of the NAD (P) H: Quinone oxidoreductase polymorphism. Ethnic variation in the prevalence of a common NAD (P) H: Quinone oxidoreductase polymorphism and its implications for anti-cancer chemotherapy.
A NAD (P) H: Quinone Oxidoreductase 1 Polymorphism Is a Risk Factor for Human Colon Cancer. Association of the GSTP1 and NQO1 Polymorphisms and Head and Neck Squamous Cell Carcinoma Risk. Association of the NAD (P) H: Quinone Oxidoreductase 609C3T Polymorphism with a Decreased Lung Cancer Risk.
Association of NAD (P) H: Quinone oxidoreductase 1 (NQO1) C609T polymorphism with esophageal squamous cell carcinoma in a German Caucasian and a northern Chinese population. Identification of NQO1 and GSTs genotype frequencies in Bulgarian patients with Balkan endemic nephropathy. Influence of CYP1A1, GSTM1, GSTT1, and NQO1 Genotypes and Cumulative Smoking Dose on Lung Cancer Risk in a Swedish Population. Genetic polymorphism analysis of NAD (P) : Quinone oxidoreductase 1 in different Iranian ethnic groups. Animal pain models display an increased presence of reactive astrocytes in the spinal cord, but in contrast to neurons, little is known about how they contribute to abnormal pain sensation. To obtain a proper model for relating the toxicity values of aliphatic carboxylic acids to their structural properties a genetic algorithm (GA) coupled with the partial least-squares (PLS) method were utilized. The selected descriptors and the orders chosen for them are shown to be good for assessing the toxicity of aliphatic carboxylic acids. Highly efficient transgenic expression was observed after DNA electrotransfer with 100-fold increase in fluorescent intensity. We hypothesize that TIMP-1 high tumors are less sensitive to chemotherapy and accordingly that high tumor tissue levels are associated with shorter survival. TIMP-1 was analyzed as a continuous variable and as a dichotomized one using the median TIMP-1 concentration as a cut point between high and low TIMP-1 groups. Preparation of ISCOMs was done by dialysis and subsequent purification in a sucrose density gradient. Transgene insertion had occurred only at the GLIS3 locus where a single complete copy of the transgene was identified in intronic sequences in opposite direction. A standardized superficial thermal injury was elicited by a heating thermode (49°C) applied to the skin for 5 min.
Hyperammonemia has been suggested to inhibit tricarboxylic acid (TCA) cycle activity, thus affecting energy metabolism.
MBL gene (MBL2) variants with between 12 to 25% allele frequency in Caucasian and other populations, result in markedly reduced expression of functional protein. Mean MBL levels were compared between genotypic groups and multivariate regression was used to determine other independent factors influencing MBL2 expression. The NQO1 is capable of maintaining these quinones in their reduced form, and therefore, detoxifies them.
This name originated from Vindhya Range, which is a range of older rounded mountains and hills in the west-central Indian subcontinent, which separates the Indian subcontinent into northern India (the Indo-Gangetic plain) and southern India. The PCR products of wild-type allele (CC) were 172 bp long and were undigestable by Hinf I at standard condition.
This fact led us to study the frequency of NQO1 in a population of Vindhyan region (Central India). Singh, Head, Blood Bank, Sanjay Gandhi Hospital, Rewa (MP) for the generous gift of blood samples, and Dr. However, astrocytes are now beginning to receive greater attention, and as new information is emerging, it appears that astrocytes undertake critical roles in manifesting pathological pain. Here, we present a new splice variant that is present in human brain as demonstrated by reverse transcription PCR.
The fluorescent signal peaked 1 week after transfection and returned to background level within 4 weeks.
We analyzed the benefit of adjuvant CMF and anthracyclines in univariate and multivariable survival models; endpoints were disease-free (DFS) and overall survival (OS). The penetration pathways of acridine-labeled ISCOMs were visualized using confocal laser scanning microscopy (CLSM).
Similar and robust levels of the transgene transcript were detected in skin biopsies from all piglets and the sequence of full-length transcript was verified. Histamine in dialysate was analyzed for up to 2 h after the injury using two different analytical methods. Furthermore, it has been suggested that catabolism of the branched-chain amino acid isoleucine may help curb the effect of hyperammonemia by by-passing the TCA cycle block as well as providing the carbon skeleton for glutamate and glutamine synthesis thus fixating ammonia. Prospective epidemiologic studies, including a nested, case-control study from the present population, have demonstrated the ability of MBL2 genotypes to predict complications of atherosclerosis,. Heterozygous condition (CT) appeared as 172, 131 and 41 bp long DNA fragments were produced after digestion with Hinf I.
Our study pointed at some important features of Hindu population, which were unknown until this study. Suraksha Agarwal, Head of Medical Genetics Division, Sanjay Gandhi Post Graduate Institute of Medical sciences, Lucknow (UP) for providing assistance in genotyping studies. Through the secretion of diffusible transmitters, such as interleukins, ATP, and NO, astrocytes may augment primary afferent neuronal signaling or sensitize second order neurons in the spinal cord. Heterologous expression in Xenopus laevis oocytes revealed a 30-mV shift in the voltage dependence of activation to more depolarized potentials and slower activation together with faster deactivation kinetics compared to hKv11.1.

Transmission electron microscopy (TEM) was used to evaluate the ultrastructural changes in the skin after application of the ISCOMs with or without hydration. Consistent with PDGFbeta promoter function, high levels of transgene expression, including high level of the corresponding protein, was observed in brain tissue and not in heart or liver tissues.
Here we present novel results describing [U-13C]isoleucine metabolism in muscle and brain analyzed by mass spectrometry in bile duct ligated rats, a model of chronic hepatic encephalopathy, and discuss them in relation to previously published results from neural cell cultures. The genetic control of MBL2 expression is complex and genetic background effects in specific populations are largely unknown. The C 609 T effectively inactivates the enzyme due to decreased catalytic activity and stability of NQO1 protein. Blood samples were drawn by intravenous injection and 3-5 ml of blood was collected in ethylenediamine tetraaceticacid (EDTA) containing bowls and was stored at -20ºC until use.
The null alleles (TT) were detected as the 131 and 41 bp long fragments were produced after digestion with Hinf I at standard condition. In addition, astrocytes might lead to altered pain perception by a direct modulation of synaptic transmission between neurons in the nociceptive pathway or through the creation of astrocytic networks capable of transducing signals for extended distances across and along the spinal cord. Further, we have cloned and electrophysiologically characterized two splice variants of hKv11.3. Transcutaneous permeation of the model compound, methyl nicotinate, was evaluated in diffusion cells. A rough estimate predicts that accumulation of the A? peptide in the brain may develop at the age of 1–2 years. The metabolism of [U-13C]isoleucine in muscle tissue was about five times higher than that in the brain which, in turn, was lower than in corresponding cell cultures. Genomic DNA was extracted from whole blood by a slight modification of salting out procedure described by Miller and coworkers. Future research in astrocyte activation and signaling may therefore reveal novel drug targets for managing pathological pain. In vivo bio-imaging using the novel Katushka fluorescent protein enables excellent evaluation of the transfection efficacy, and spatial distribution, but lacks long-term stability.
The prepared ISCOMs were 42–52 nm in diameter as evaluated by dynamic light scattering with zeta potentials of ?33 to ?26.1 mV.
It could be due to random mixing of various ethnic groups in Maharashtrian population in the modern age. In rat brain, differential labeling patterns in glutamate and glutamine suggest that isoleucine may primarily be metabolized in the astrocytic compartment which is in accordance with previous findings in neural cell cultures. But increase in heterozygosity surprised us because the marriage between the close communities is common among the Maharashtrians.Our results showed that the frequencies of different polymorphs of NQO1 genes are statically distinct in our population than in Caucasian and other Asian populations, although the differences are much evident between our population and other Asian populations [Table - 3],[Figure - 3]. The different current characteristics of the isoforms presented in this work may contribute to the regulation of neuronal excitability. Penetration of acridine into skin was greatly increased by incorporation into ISCOMs as visualized by CLSM.
Lastly, in rat brain the labeling patterns of glutamate, aspartate and GABA do not suggest any significant inhibition by ammonia of TCA cycle activity which corresponds well to findings in neural cell cultures. Branched-chain amino acids including isoleucine are used for treating hepatic encephalopathy and the present findings shed light on the possible mechanism involved.
All the values were nonsignificant, which showed that the frequency distribution of C and T alleles in both the groups was statically not Significant [Table - 2].
Ultrastructural changes of the intercellular space in the stratum corneum after exposure of ISCOMs were observed on micrographs, especially for hydrated skin.
The low turn-over of isoleucine in rat brain suggests that this amino acid does not serve the role of providing metabolites pertinent to TCA cycle function and hence energy formation as well as the necessary carbon skeleton for subsequent ammonia fixation in hyperammonemia. In conclusion, cutaneous application of ISCOMs leads to increased penetration of hydrophobic model compounds through human stratum corneum and thus shows potential as a transcutaneous delivery system.
The higher metabolism of isoleucine in muscle could, however, contribute to ammonia fixation and thus likely be of value in the treatment of hepatic encephalopathy. The increased penetration seems to be reflected by a change in the intercellular space between the corneocytes, and the effect is most likely caused by the components of the ISCOMs rather than intact ISCOMs. This indicates that NQO1 plays a role in p53 stabilization, which has a crucial role in cell cycle regulation. But an increase in TT (mutant) genotype was observed in our population and in two Iranian ethnic groups (Fars and Mazzandarani) than in Turks and other world populations. A 100-bp gene DNA ladder (Genetix, India) was run concurrently as a molecular weight marker. These results did not surprise us because in calculation of NQO1 Hinf I allele, Kiyohara et al. Synthetic antioxidants such as butyrate hydroxyanisole and extracts of cruciferous vegetables, including broccoli, have been shown to be potent inducers of NQO1. This inducibility has led to the suggestion that NQO1 can play an important role in cancer chemoprevention and therapy. This finding suggests that the Indian population cannot be correlated with the rest of the Asian population.

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