Chemometric modeling of pharmaceuticals for partitioning between sludge and aqueous phase during the wastewater treatment process.

Computational techniques, such as quantitative structure-property relationships (QSPRs), can play a significant role in exploring the important chemical features essential for the degree of sorption or sludge/water partition coefficient (Kd) towards sewage sludge of wastewater treatment process to evaluate the environmental consequence and risk of pharmaceuticals. The current research work aims to construct a predictive QSPR model for the sorption of 148 diverse active pharmaceutical ingredients (APIs) in sewage sludge during wastewater treatment. For the development of the model, we employed easily computable 2D descriptors as independent variables. The model has been developed following the Organization for Economic Cooperation and Development's (OECD) guidelines. It has undergone internal and external validation using a variety of methodologies, as well as been tested for its applicability domain. A measure of hydrophobicity, i.e., MLOGP2, showed the most promising contribution in modeling the sorption coefficient of APIs. Among other parameters, the number of tertiary aromatic amines, the presence of electronegative atoms like N, O, and Cl, the size of a molecule, the number of aromatic hydroxyl groups, the presence of substituted aromatic nitrogen atoms and alkyl-substituted tertiary carbon atoms were also found to be influential for the regulation of solid water partition coefficient of APIs during the wastewater treatment process. The statistical validity tests performed on the developed partial least squares (PLS) model showed that it is statistically evident, robust, and predictive (R2Train = 0.750, Q2LOO = 0.683, Q2F1 = 0.655, Q2F2 (or R2Test) = 0.651). In addition, the predictivity of the constructed model was further inspected by using the "prediction reliability indicator" tool for 14 external APIs.

Exploring quantitative structure-property relationship models for environmental fate assessment of petroleum hydrocarbons.

The rate and extent of biodegradation of petroleum hydrocarbons in the different aquatic environments is an important element to address. The major avenue for removing petroleum hydrocarbons from the environment is thought to be biodegradation. The present study involves the development of predictive quantitative structure-property relationship (QSPR) models for the primary biodegradation half-life of petroleum hydrocarbons that may be used to forecast the biodegradation half-life of untested petroleum hydrocarbons within the established models' applicability domain. These models use easily computable two-dimensional (2D) descriptors to investigate important structural characteristics needed for the biodegradation of petroleum hydrocarbons in freshwater (dataset 1), temperate seawater (dataset 2), and arctic seawater (dataset 3). All the developed models follow OECD guidelines. We have used double cross-validation, best subset selection, and partial least squares tools for model development. In addition, the small dataset modeler tool has been successfully used for the dataset with very few compounds (dataset 3 with 17 compounds), where dataset division was not possible. The resultant models are robust, predictive, and mechanistically interpretable based on both internal and external validation metrics (R2 range of 0.605-0.959. Q2(Loo) range of 0.509-0.904, and Q2F1 range of 0.526-0.959). The intelligent consensus predictor tool has been used for the improvement of the prediction quality for test set compounds which provided superior outcomes to those from individual partial least squares models based on several metrics (Q2F1 = 0.808 and Q2F2 = 0.805 for dataset 1 in freshwater). Molecular size and hydrophilic factor for freshwater, frequency of two carbon atoms at topological distance 4 for temperate seawater, and electronegative atom count relative to size for arctic seawater were found to be the most significant descriptors responsible for the regulation of biodegradation half-life of petroleum hydrocarbons.

Exploring QSAR modeling of toxicity of chemicals on earthworm.

Earthworm provides sustainability towards the agroecosystem which can be degraded day by day by the extensive use of pesticides (e.g., fungicides, insecticides and herbicides). The present study attempts to develop a predictive quantitative structure-activity relationship (QSAR) model for toxicity of pesticides to earthworm in order to give a suitable guidance for designing new analogues with lower toxicity by exploring the important chemical features which are required to develop safer alternatives. The QSAR model was developed by using the negative logarithm of lethal concentration (pLC50) values of pesticides towards earthworm. We have used various 2D descriptors along with extended topochemical atom (ETA) indices as independent variables for the development of the model. The developed partial least squares (PLS) model was subjected to statistical validation tests proving that the model is statistically reliable and robust (R2 = 0.765, Q2 = 0.614, Q2F1 = 0.734, Q2F2 = 0.713). The contributing descriptors in the model suggested that the pesticides may affect the earthworm nucleic acid through various physicochemical interactions including hydrophobicity, hydrogen bonding, electron donor acceptor complex formation, π-π stacking interaction and charge transfer complex formation.

Exploring QSPR modeling for adsorption of hazardous synthetic organic chemicals (SOCs) by SWCNTs.

In order to understand the physicochemical properties as well as the mechanisms behind adsorption of hazardous synthetic organic chemicals (SOCs) onto single walled carbon nanotubes (SWCNTs), we have developed partial least squares (PLS)-regression based QSPR models using a diverse set of 40 hazardous SOCs having defined adsorption coefficient (logK). The models were extensively validated using different validation parameters in order to assure the robustness and predictivity of the models. We have also checked the consensus predictivity of all the individual models using "Intelligent consensus predictor" tool for possible enhancement of the quality of predictions for test set compounds. The consensus predictivity of the test set compounds were found to be better than the individual models based on not only the MAE based criteria (MAE(95%) = Good) but also some other validation parameters (Q2F1 = 0.938, Q2F2 = 0.937). The contributing descriptors obtained from the QSPR models suggested that the hazardous SOCs may get adsorbed onto the SWCNTs through hydrophobic interaction as well as hydrogen bonding interactions and electrostatic interaction to the functionally modified SWCNTs. Thus, the developed models may provide knowledge to scientists to increase the efficient application of SWCNTs as a special adsorbent, which may be useful for the management of environmental pollution.

Effects of organoselenium compound 2-(5-selenocyanato-pentyl)-benzo[de]isoquinoline 1,3-dione on cisplatin induced nephrotoxicity and genotoxicity: an investigation of the influence of the compound on oxidative stress and antioxidant enzyme system.

Cisplatin is one of the most active cytotoxic agents used in the treatment of cancer. However, cisplatin therapy is also associated with severe side effects like nephrotoxicity and genotoxicity. Free oxygen radicals are known to play a major role in cisplatin induced toxicities. Selenium is believed to be an important trace element and dietary antioxidant because of its ability to scavenge free oxygen radicals, thereby preventing cells from oxidative stress. The purpose of this study is to evaluate the protective role of a novel naphthalimide based organoselenium compound 2-(5-selenocyanato-pentyl)-benzo[de]isoquinoline 1,3-dione against cisplatin induced toxicities in Swiss albino mice. Cisplatin was administered intraperitoneally (5 mg/kg b.w.) and the organoselenium compound was given by oral gavages (3 mg/kg b.w.) in concomitant and pretreatment schedule. The results showed that the test compound substantially reduced cisplatin induced reactive oxygen species generation and lipid peroxidation in kidney as well as blood urea nitrogen and creatinine levels in serum. Treatment with organoselenium compound was also able to restore the renal antioxidant system by modulating the cisplatin induced depleted activities of glutathione S-transferase, thioredoxin reductase, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione level. In addition, the organoselenium compound could efficiently minimize cisplatin induced chromosomal aberrations in bone marrow cells and extent of DNA damage in lymphocytes. Furthermore, the chemoprotective efficacy of the compound against cisplatin induced toxicity was confirmed by histopathological evaluation. The results suggest that the organoselenium compound has the potential to protect against cisplatin induced nephrotoxicity and genotoxicity in part by scavenging reactive oxygen species and by up regulating the antioxidant enzyme system.

Influence of novel naphthalimide-based organoselenium on genotoxicity induced by an alkylating agent: the role of reactive oxygen species and selenoenzymes.

OBJECTIVE: The protection conferred by a series of synthetic organoselenium compounds against genotoxicity and oxidative stress induced by a reference mutagen cyclophosphamide (CP) was assessed. METHOD: Genotoxicity was induced in mice by CP treatment (25 mg/kg b.w.) for 10 consecutive days. Organoselenium compounds (3 mg/kg b.w.) were administered orally in a concomitant and pretreatment schedule. DNA damage in peripheral blood lymphocytes and frequency of chromosomal aberration in the bone marrow cells were measured. Liver tissues were collected for analysis of the activity of antioxidant and detoxifying enzymes, lipid peroxidation (LPO) level, glutathione content, and histopathology. RESULTS: Exposure to CP not only led to a significant increase in the percent of chromosomal aberration and DNA damage, but also enhanced generation of hepatic reactive oxygen species (ROS) and LPO level. The organoselenium compounds demonstrated marked functional protection against CP-induced genotoxicity. DNA damage and chromosomal aberration along with ROS generation were attenuated in the organoselenium-treated mice compared with the CP-treated control mice. CP caused marked depression in the activities of the selenoenzymes (glutathione peroxidase (GPx) and thioredoxin reductase (TRxR)) and other detoxifying and antioxidant enzymes, while treatment with organoselenium compounds restored all these activities towards normal. DISCUSSION: The protective effect of these compounds may be primarily associated with the improvement of the activity of antioxidant and detoxifying enzymes (including the selenoenzymes, GPx, and TRxR) that are known to protect the DNA and other cellular components from oxidative damage.

Screening for thalassemia and other hemoglobinopathies in a tertiary care hospital of West Bengal: implications for population screening.

Hemoglobinopathies are common genetic disorders of hemoglobin, which can be prevented by population screening and offering genetic counseling. In absence of population-based screening for hemoglobinopathies, the hospital-based diagnosis register provide idea about the extent of problem in the community. The present study was undertaken to find out the burden of hemoglobinopathies and spectrum of this disorders among the population who were screened in the hospital-based screening program. A record-basedanalysis of subjects who underwent screening for hemoglobinopathies in Burdwan Medical College and Hospital over a period of 3 years and 4 months revealed that overall 29.3% of subjects were positive for hemoglobinopathies. Beta thalassemia heterozygous was the most commonhemoglobinopathy in this region closely followed by hemoglobin E heterozygous. In view of high prevalence of hemoglobinopathies in this region, a routine premarital screening program is needed for identification and prevention of high-risk marriages.

Lewandowsky and lutz dysplasia: report of two cases in a family.

Lewandowsky and Lutz dysplasia, also known as epidermodysplasia verruciformis (EV), is an inherited disorder in which there is widespread and persistent infection with human papilloma virus, defect in cell-mediated immunity and propensity for malignant transformation. Differential clinical and histopathologic evolutions of lesions in two cases of familial EV are compared and discussed in detail. Cases were followed up for 7 years. Detailed history, clinical features and investigations, including skin biopsy from different sites at different times, were examined. Generalized pityriasis versicolor like hypopigmented lesions in both the cases, together with variable pigmented nodular actinic keratosis like lesions on sun-exposed areas, were present. Multiple skin biopsies done from various sites on different occasions revealed features typical of EV along with lesions, i.e., actinic keratosis, Bowen's disease, basal and squamous cell carcinoma, in the elder sibling. However, skin biopsy of the other sibling showed features of EV and seborrheic keratosis only till date. This study reveals that the disease progression is variable among two individuals of the same family. Malignant lesions were seen only on sun-exposed areas and may be associated with other skin lesions or infections such as angiokeratoma of Fordyce and tinea cruris, as seen in this report.

Forensic diagnosis and classification of snakebite (neurotoxic and haemotoxic) from renal changes at autopsy: morphological and histological determinants using a semi-quantitative method.

Mortality due to poisonous snakebite is an emerging public health concern. Of late, snakebite has drawn global attention. Snakebite is a well-known cause of renal pathology especially in the haemotoxic group. Deaths due to renal failure are very common in envenomation due to poisonous snakebite. In this investigation our aim was to devise autopsy-proven diagnostic criteria of snakebite from the renal changes to confirm and classify the type of snakebite in forensic casework. That would be of practical help to the forensic pathologist with access to limited resources. An arbitrary scoring system from histology was adopted for the present semi-quantitative analysis. The scoring system (with scores from 0 to 5) developed by the present study was effective, valid and was able to distinguish between snakebite and control. The score obtained at histology in cases of snakebite was significantly different from the control group (Mann-Whitney U = 71.5; P = 0.011). Using stepwise linear discriminant function (DF) analysis, the score (Mukhopadhyay's score [MS]) was seen to be the only predictor of the type of snakebite. This model (DF = 1.05 x MS-1.78) could correctly classify 93.3% of the cases into neurotoxic and haemotoxic variety of offending snake. This is an effective, cheap and easy semi-quantitative method of distinguishing neurotoxic and haematoxic snakes from the renal changes at autopsy. It would be useful for practical application in centres where sophisticated biochemical or immunological analyses are not available due to limited resources.

Synthesis and biological evaluation of novel spiro 6-methoxytetralin-1,3'-pyrrolidine based organoselenocyanates against cadmium-induced oxidative and hepatic damage in mice.

A series of novel organoselenocyanate compounds (6a-d) having spiro[tetralin-1,3'-pyrrolidine] moiety were synthesized. The compounds were evaluated for their inhibitory activity against cadmium- (Cd) induced toxicity in Swiss Albino mice. All the compounds (6a-d) inhibited the level of lipid peroxidation (LPO) and upregulated the activity of glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels in treatment group in comparison to the untreated Cd control group. Serum transaminase activities, e.g., alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also significantly lowered in the compound-treated mice. Elongation of the alkyl chain length bearing the selenocyanate (SeCN) active group enhanced the potency of the compounds, 6d being the most active one (6d>6c>6b>6a).

Prognostic value of AgNOR in benign and malignant lesions of larynx in a rural medical college hospital, Burdwan, West Bengal.

AgNOR counting is a useful proliferative marker in different malignant lesions and it also acts as a good prognostic indicator in rural hospital. Fifty-three cases of benign and malignant lesions of larynx were examine using AgNOR distribution in routinely processed paraffin embedded histological tissue sections. Significant differences were found between benign lesion, dysplasia (p > 0.10) and carcinoma (p > 0.10). Mean AgNOR count was 2.41% in dysplasia and 3.71% in malignant lesion. This value was high in poorly differentiated squamous cell carcinoma (4.17%) and also in supraglottic type of laryngeal squamous cell carcinoma which associated with lymph node metastasis. Thus proliferative marker AgNOR may be a prognostic factor and might be of clinical value as predictor of lymph node metastasis in supraglottic type of laryngeal squamous cell carcinoma.

Dedifferentiated papillary carcinoma of thyroid in an adolescent girl--a case report.

Dedifferentiated papillary carcinoma of thyroid shows combined histopathological features of classical papillary carcinoma and anaplastic carcinoma. This is a very rare tumour in adolescence. This prompted the authors to report this case.