Synthesis, biological evaluation and molecular docking studies of novel quinazolinones as antitubercular and antimicrobial agents.

In the present study, a series of novel quinazolinone hybrids, viz. triazepino-quinazolinones 4, thiazolo-triazolo-quinazolinones 7 and triazolo-quinazolinones 8 have been synthesized from the key intermediate 3-(substituted phenyl)-2-hydrazinoquinazolin-4(3H)-ones 3. All the newly synthesized compounds were characterized by means of spectral (IR, 1H NMR, 13C NMR) and elemental analysis. The target compounds were biologically screened for their in vitro antimicrobial and antitubercular activities against pathogenic strain. The results of bioassay demonstrated that some of the compounds exhibited pronounced antimicrobial activity comparable to that of standard drugs tested under similar conditions. Compounds 4c, 4e, 7e and 8b showed relatively very good inhibitory activity against pathogenic bacteria with minimum inhibitory concentration (MIC) of 2.6 µg/mL, 5.2 µg/mL, while the rest of the compounds showed moderate activity. Compounds 4c and 8b were found to be nearly equipotent with ciprofloxacin against P. aeruginosa with MIC 5.2 µg/mL, while compound 8b was more potent against pathogenic bacteria S. aureus. It is very remarkable that four compounds, 4c, 4e, 7e and 8b showed pronounced antifungal activity against selected pathogenic fungi, A. niger, C. albicans with MIC 2.6 µg/mL and 5.2 µg/mL. The antitubercular activity of synthesized compounds reveal that compound 8b showed better activity than the other compounds with a MIC of 5.2 µg/mL against M. tuberculosis (H37Rv). Molecular docking studies of the compounds were performed to rationalize the inhibitory properties of these compounds and results showed that these compounds have good binding energy and better binding affinity within the active pocket, thus these compounds may be considered as potent inhibitors towards selective targets.

Unconventional strategies in the battle of focal and segmental glomerulosclerosis.

A 24-year-old male presented with classic features of the nephrotic syndrome. An initial renal biopsy revealed minimal change disease and thereafter, a second biopsy showed features of focal and segmental glomerulosclerosis. There was no response to conventional immunosuppression, and the patient had to be given rituximab; in spite of this, he went on to develop end-stage renal disease. He continued to have heavy proteinuria leading to severe hypoalbuminemia, thrombosis, infections, and malnutrition, placing the patient in a life-threatening situation. Bilateral renal ablation with embolization of both kidneys with coiling was done at one setting, which finally resolved the proteinuria in the patient. He then underwent a living-related renal transplant, developing recurrence immediately post-transplant. He was again given rituximab along with tacrolimus, mycophenolate mofetil, and prednisolone. There was no response to rituximab, and the patient underwent plasmapheresis, which leads to complete remission. An arteriovenous fistula was created post-transplant to facilitate regular plasmapheresis.

Evans syndrome and its link with systemic lupus erythematosus.

Evans syndrome is a rare syndrome associated with the presence of autoimmune hemolytic anemia and simultaneous or sequential development of thrombocytopenia. It was first described by Evan and Duane in 1951. It is one of the rare presenting features of autoimmune disorders, especially systemic lupus erythematosus (SLE), and sometimes may even precede the onset of disease. Primary Evans syndrome with no cause is very rare and is seen in children. Here, we describe a case of secondary Evans syndrome with severe hemolytic anemia leading to acute kidney injury and recovery thereafter only to develop lupus nephritis a few months later. This is one of the rare presentations of SLE and there are only anecdotal case reports.

Development of high-voltage pulse generator with variable amplitude and duration.

A high voltage pulse generator with variable amplitude (100-3000 V) and duration (100-2000 µs) has been designed and developed. The variable duration pulse has been generated by adopting a simple and novel technique of varying the turn off delay time of a high voltage Metal Oxide Semiconductor Field Effect Transistor (MOSFET) based switch by varying external gate resistance. The pulse amplitude is made variable by adjusting biasing supply of the high voltage switch. The high voltage switch has been developed using a MOSFET based stack of 3 kV rating with switching time of 7 ns.

Genes tagging and molecular diversity of red rot susceptible/tolerant sugarcane hybrids using c-DNA and unigene derived markers.

Sugarcane is an important international commodity as a valuable agricultural crop especially in tropical and subtropical countries. Two bulked DNA used to screen polymorphic primers from commercial hybrids (varieties) with moderately resistant and highly susceptible to red rot disease. Among 145 simple sequence repeat and unigene primers screened, 37 (25%) were found to be highly robust and polymorphic with Polymorphism Information Content values ranging from 0.50 to 1.00 with the mean value of 0.82. Among these microsatellites, twenty one were used in the study of genetic relationships and marker identification in sugarcane varieties for red rot resistance. A total of 105 polymorphic DNA bands were identified, with their fragment size ranging from 54 to 1,280 bp. Jaccard's similarity coefficient value recorded between closely related hybrids was 0.986 while lowest coefficient value of 0.341 was detected with distantly related hybrids. The average similarity coefficient among these hybrids was 0.663. Cluster analysis resulted in a dendrogram with two major clusters separating the moderately resistant varieties from highly susceptible varieties. Three group specific fragments amplified by unigene Saccharum microsatellite primers viz; two markers UGSM316(850) and UGSM316(60) were closely associated with moderately resistant varieties by appearing bands in this region but the bands were absent in highly susceptible varieties. Similarly UGSM316(400) marker was tightly linked with highly susceptible varieties by amplifying uniformly in sugarcane varieties showing highly susceptible reaction to red rot but it was absent in moderately resistant varietal groups. Validation of red rot resistance/susceptibility associated markers on a group of different mapping populations for red rot resistant/susceptible traits is in progress.

Template synthesis, spectroscopic characterization and preliminary insulin-mimetic activity of oxovanadium(IV) complexes with N2O2 diazadioxa macrocycles.

A new series of diazadioxa oxovanadium(IV) macrocyclic complexes of type [VO(mac)]SO(4) have been synthesized via the condensation reaction of a 3-(phenyl/substituted phenyl)-4-amino-5-hydrazino-1,2,4-triazole (H(2)L) with salicylaldehyde/2-hydroxyacetophenone and 1,4-dibromobutane in the presence of oxovanadium(IV) sulfate in ethanol. All the newly synthesized compounds were characterized on the basis of elemental analyses, conductance measurements, magnetic properties, spectral (UV-Vis, IR, EPR) and XRD studies. The particle size of the complexes has been calculated from XRD spectra using Debye-Scherrer formula and these are found to be in 31-32 nm range. The efficacy of two macrocyclic complexes was also studied in streptozotocin-induced diabetic rats over a period of 30 days. The administration of these complexes in diabetic rats reversed the diabetic effect due to their insulin-mimetic effects.

Development of high-voltage pulse-slicer unit with variable pulse duration for pulse radiolysis system.

A high-voltage pulse-slicer unit with variable pulse duration has been developed and integrated with a 7 MeV linear electron accelerator (LINAC) for pulse radiolysis investigation. The pulse-slicer unit provides switching voltage from 1 kV to 10 kV with rise time better than 5 ns. Two MOSFET based 10 kV switches were configured in differential mode to get variable duration pulses. The high-voltage pulse has been applied to the deflecting plates of the LINAC for slicing of electron beam of 2 µs duration. The duration of the electron beam has been varied from 30 ns to 2 µs with the optimized pulse amplitude of 7 kV to get corresponding radiation doses from 6 Gy to 167 Gy.

Role of preoperative chemotherapy in squamous cell carcinoma of esophagus in kashmir, a cancer belt - a pilot study.

BACKGROUND: Esophageal carcinoma is the fifth leading gastrointestinal malignancy and is one of the leading causes of cancer related death. Despite improvements in surgical technique over the last few decades, the outcome has been dismal, with overall 5 year survival not exceeding 15%-25%. AIMS AND OBJECTIVES: To evaluate the effect of preoperative chemotherapy on resectability, complication rate and overall survival in patients with squamous cell carcinoma esophagus. MATERIALS AND METHODS: 50 patients with histologically confirmed squamous cell carcinoma (SCC), with localised or loco-regional disease (stage 4 excluded) were divided into 2 groups. Group A patients were subjected to 2-3 cycles of pre-operative chemotherapy (5FU-CDDP), whereas Group B patients were directly operated on. OBSERVATIONS: 3 (12%) patients in group A showed complete pathological response to chemotherapy and 18 (72%) showed a partial response, with four patients (16%) showing resistance to chemotherapy. There was no statistically significant difference in terms of response to chemotherapy with respect to degree of differentiation of tumor. There was no significant difference in the overall resectability rates between the two groups (p > 0.05), but R0 resection was achieved in 20 (80%) of group A and only 10 (40%) of group B, the difference being statistically significant (p < 0.05). The rate of overall complications was also much higher in the control group. Initially there was no significant difference in the survival between the two groups, but later (20 months) the study group showed a slight non-significant advantage. CONCLUSION: Preoperative chemotherapy significantly increases the rate of R0 resection without significantly increasing postoperative morbidity and mortality in patients with squamous cell carcinoma of esophagus. However, to assess the impact on survival the study period needs to be extended.

Design of microcontroller based system for automation of streak camera.

A microcontroller based system has been developed for automation of the S-20 optical streak camera, which is used as a diagnostic tool to measure ultrafast light phenomenon. An 8 bit MCS family microcontroller is employed to generate all control signals for the streak camera. All biasing voltages required for various electrodes of the tubes are generated using dc-to-dc converters. A high voltage ramp signal is generated through a step generator unit followed by an integrator circuit and is applied to the camera's deflecting plates. The slope of the ramp can be changed by varying values of the capacitor and inductor. A programmable digital delay generator has been developed for synchronization of ramp signal with the optical signal. An independent hardwired interlock circuit has been developed for machine safety. A LABVIEW based graphical user interface has been developed which enables the user to program the settings of the camera and capture the image. The image is displayed with intensity profiles along horizontal and vertical axes. The streak camera was calibrated using nanosecond and femtosecond lasers.

New synthesis of nematocidal natural products dithiocynates thiocyanatin A and 1,8,16-trihydroxyhexadecane.

A new and short synthesis of nematocidal natural products, thiocyanatin A and 1,8,16-trihydroxyhexadecane, from readily available starting compounds 1,7-heptanediol and 1,9-nonanediol in six steps is described.

Three-dimensional study on the effect of organophosphate pesticide 'monocrotophos' on lens of fish and its recovery.

The present studies are based on the feedback provided by fish farmers practicing composite fish culture of carps. According to them, fish habitats are affected by pesticides draining from agricultural fields into their catchments, especially during the rainy season. The lenses of most of the cultured fish became opaque, resulting in poor overall growth. In the literature, there was mounting evidence of pesticide toxicity involving multiple tissues. However, the fish visual system has never been investigated particularly from the toxicological perspective. In this regard, we carried out comparative toxicological studies on the lens of Cyprinus carpio communis using three different sublethal concentrations (0.038, 0.062 and 0.126 p.p.m.) of monocrotophos along with untreated controls for 30 days. Lenses from all the groups were extracted and preserved in gluteraldehyde and osmium tetraoxide and dehydrated in increasing grades of acetone. After dehydration, tissues were conducted with gold to observe under SEM. The fish exposed to monocrotophos developed cataract. Furthermore, when fish from the monocrotophos-treated tanks were transferred to normal environmental conditions for the next 60 days, progressive lens degeneration was noted. To conclude, monocrotophos induces irreversible cataractous changes in the lens of C. carpio communis. The fish visual system has many similarities to mammals and may serve as a good model for comparative toxicologic and ophthalmologic studies.

A high voltage programmable ramp generator.

In this paper, a ramp generator with programmable slope is presented. It consists of a high voltage step generator, followed by integrator. The capacitor and inductor in the integrator are designed such that they can be varied by a microcontroller. This circuit generates two bipolar ramps with fastest speed <1 ns and provides continuous speed variation from 6 to 30 ns for a ramp of 500 V. This is being developed as a part of automated streak camera for deflection of electron beam.

Impact of low dose of organophosphate, monocrotophos on the epithelial cells of gills of Cyprinus carpio communis Linn.--SEM study.

The paper deals with the deleterious changes at ultrastructural level of the epithelial cells of gills of Cyprinus carpio communis Linn. upon exposure to 1/10th of LC50 of monocrotophos which is considered to be insignificant concentration from toxicological point of view. The gills of the fish are the primary corridor formolecularexchange between the internal milieu of a fish and its environment. Gills perform numerous functions such as oxygen uptake and CO2 excretion, osmoregulation, acid-basic balance, excretion of nitrogenous compounds and taste. Hazardous chemicals present in water may alter the morphology of the epithelial cells of gills of the fish, which may affect the process of diffusion of gases and ultimately the overall health of the fish. To prove this fact Cyprinus carpio communis Linn. was kept in water for 30 days having low concentration of 0.038 ppm (1\10th of LC50) of monocrotophos and an attempt was made to study the different types of degenerations produced in the epithelial cells of gills as compared to the normal epithelial cells of gills of this culturable fish using Scanning Electron Microscope (SEM) technique. The ultrastructural changes due to the toxic exposure at finer scale were thinning of microridges, upliftment of epithelial cells, development of hyperplasia, decrease in the density of mucous cells which are considered to be the first line of defence and total dystrophy of epithelial tissue. Thus, it is opined that a low concentration of monocrotophos has the potential to bring different type of degenerations at finer scale hence affecting the fish's health drastically and altering the fitness of the fish in water even having insignificant amount of this toxicant in the ambient water

Clinicopathological and radiological evaluation of cervical lymph node metastasis in head and neck malignancies.

The cervical lymphadenopathy due to metastasis carry poor prognosis. The status of cervical nodes is of critical interest to surgical, radiation and medical oncologists who manage patients with head and neck cancers. We conducted a prospective randomized study to assess the role of palpation, ultrasound and CT in detection of cervical metastasis in 25 patients presented to us with head and neck malignancy irrespective of cervical nodal status. It was observed that clinical examination was least sensitive (73.33%) when compared with computerized tomography (80%) and ultrasound (93.93%). The computerized tomography was found to be most specific (90%) when compared to clinical examination or ultrasonography (70% each).

Auditory brainstem responses in neonatal hyperbilirubinemia and effect of therapy.

UNLABELLED: Objectives; To determine the effect of neonatal hyperbilirubinemia on auditory brainstem responses (ABRs) and evaluate ABR responses to lowering of bilirubin levels. STUDY DESIGN: prospective case control trial SETTING: tertiary referral center. PATIENTS: 60 neonates (40 cases & 20 controls). Term appropriate for date(AFD) neonates with uncomplicated birth history and bilirubin level of ≥ 13 mg/dL were included as cases, those with bilirubin value of < 13 mg/dL were taken as controls.Interventions; First BERA examination was carried out within 24 hrs of the diagnosis of hyperbilirubinemia and repeat examination was done when total serum bilirubin came down to < 13 mg/dL with treatment. Comparisons were made between cases (before & after therapy) and controlResults; No abnormality in neonates with bilirubin < 18 mg/dL. Abnormal ABRs were observed in 24(60%) of the 40 cases studied, with therapy it reverted back to normal in 15(62%). The commonest abnormality noted was prolonged latency of wave V(42.5%), followed by prolonged latency of wave III(35%) and wave I(22.5%). Prolonged latency of wave I was found in only those with bilirubin > 20mg/dL. Inter peak latency of wave IV (Brain stem conduction time) was prolonged in 8 cases; it reverted to normal in all cases. Prolonged inter peak latency of wave I-III was observed in 7 cases, of which it reverted to normal in 6. Absent waves reappeared in 4 out of 5 cases, but abnormal amplitude ratios reverted to normal in only one of the 7 cases in which it was abnormal.Conclusions; about 60% of term A FD neonates with serum bilirubin of > 18mg/dL will demonstrate ABR changes. Most of these changes revert to normal early after therapy, indicating need for aggressive therapy in this subgroup of neonates.

Adaptation to disruption of the electron transfer pathway for Fe(III) reduction in Geobacter sulfurreducens.

Previous studies demonstrated that an outer membrane c-type cytochrome, OmcB, was involved in Fe(III) reduction in Geobacter sulfurreducens. An OmcB-deficient mutant was greatly impaired in its ability to reduce both soluble and insoluble Fe(III). Reintroducing omcB restored the capacity for Fe(III) reduction at a level proportional to the level of OmcB production. Here, we report that the OmcB-deficient mutant gradually adapted to grow on soluble Fe(III) but not insoluble Fe(III). The adapted OmcB-deficient mutant reduced soluble Fe(III) at a rate comparable to that of the wild type, but the cell yield of the mutant was only ca. 60% of that of the wild type under steady-state culturing conditions. Analysis of proteins and transcript levels demonstrated that expression of several membrane-associated cytochromes was higher in the adapted mutant than in the wild type. Further comparison of transcript levels during steady-state growth on Fe(III) citrate with a whole-genome DNA microarray revealed a significant shift in gene expression in an apparent attempt to adapt metabolism to the impaired electron transport to Fe(III). These results demonstrate that, although there are many other membrane-bound c-type cytochromes in G. sulfurreducens, increased expression of these cytochromes cannot completely compensate for the loss of OmcB. The concept that outer membrane cytochromes are promiscuous reductases that are interchangeable in function appears to be incorrect. Furthermore, the results indicate that there may be different mechanisms for electron transfer to soluble Fe(III) and insoluble Fe(III) oxides in G. sulfurreducens, which emphasizes the importance of studying electron transport to the environmentally relevant Fe(III) oxides.