Peptide receptor radionuclide therapy induced carcinoid crisis: A case report.

Peptide receptor radionuclide therapy (PRRT) is a therapeutic option in inoperable or metastatic neuroendocrine tumours (NETs). PRRT proved to be promising in prolonging survival and delaying disease progression in patients with advanced bronchopulmonary carcinoid. However, it may lead to worsening of carcinoid symptoms or even precipitate carcinoid crises. The incidence of PRRT induced carcinoid crisis would be between 1-10%. This usually takes place during the first PRRT cycle, either during the tracer infusion or 12-48 hours' post-administration. We report a 62-year-old man with underlying metastatic lung carcinoid tumour who developed carcinoid crisis at 10 hours after receiving PRRT. The carcinoid crisis was successfully treated with intravenous octreotide infusion, corticosteroid, a selective 5-HT3 receptor antagonist, parenteral ranitidine and chlorpheniramine for H1 and H2 antagonism respectively.

Synthesis, structural elucidation, antioxidant, CT-DNA binding and molecular docking studies of novel chloroquinoline derivatives: Promising antioxidant and anti-diabetic agents.

The synthesized novel chloroquinoline derivatives 1-(2-chloro-4-phenylquinolin-3-yl)ethanone (CPQE), 1-(2,6-dichloro-4-phenylquinolin-3-yl)ethanone (DCPQE), methyl 2,6-dichloro-4-phenylquinoline-3-carboxylate (MDCPQC),methyl 2-chloro-4-methylquinoline-3-carboxylate (MCMQC) were subjected to the elementary analysis like FT-IR, NMR and Mass spectra using GCMS. Also, single crystal X-ray diffraction study was executed for the compound MDCPQC. The crystal packing is stabilized by C-H…π and π-π interactions and also Chlorine-Chlorine short intermolecular contacts generating a three-dimensional supramolecular network. The antioxidant activity reduces high glucose level in the human body and hence the synthesized compounds were subjected for the estimation of antioxidant activity using DPPH method which exhibited good percentage of inhibition in comparison with ascorbic acid, a well-known anti-oxidant. The binding interaction of the chloroquinoline derivatives with calf thymus DNA (CT-DNA) has been explored by fluorescence quenching studies and molecular docking analysis has been employed to confirm the nature of binding. The prediction of pharmacological properties such as drug-likeness, molecular properties like absorption, distribution, metabolism, excretion and toxicity (ADMET) was carried out by computational studies to compare chloroquinoline derivatives with standard drug. Owing to the various potential biological activities of the quinoline compounds, molecular docking studies were also further carried out for the chloroquinoline derivatives, showing that they may act as effective anti-diabetic agents by inhibiting Glycogen Phosphorylase a protein.

Ubiquitin ligase Nedd4-2 modulates Kv1.3 current amplitude and ion channel protein targeting.

Voltage-dependent potassium channels (Kv) go beyond the stabilization of the resting potential and regulate biochemical pathways, regulate intracellular signaling, and detect energy homeostasis. Because targeted deletion and pharmacological block of the Kv1.3 channel protein produce marked changes in metabolism, resistance to diet-induced obesity, and changes in olfactory structure and function, this investigation explored Nedd4-2-mediated ubiquitination and degradation to regulate Kv1.3 channel density. Heterologous coexpression of Nedd4-2 ligase and Kv1.3 in HEK 293 cells reduced Kv1.3 current density without modulation of kinetic properties as measured by patch-clamp electrophysiology. Modulation of current density was dependent on ligase activity and was lost through point mutation of cysteine 938 in the catalytic site of the ligase (Nedd4-2CS). Incorporation of adaptor protein Grb10 relieved Nedd4-2-induced current suppression as did application of the proteasome inhibitor Mg-132. SDS-PAGE and immunoprecipitation strategies demonstrated a channel/adaptor/ligase signalplex. Pixel immunodensity was reduced for Kv1.3 in the presence of Nedd4-2, which was eliminated upon additional incorporation of Grb10. We confirmed Nedd4-2/Grb10 coimmunoprecipitation and observed an increased immunodensity for Nedd4-2 in the presence of Kv1.3 plus Grb10, regardless of whether the catalytic site was active. Kv1.3/Nedd4-2 were reciprocally coimmunoprecipated, whereby mutation of the COOH-terminal, SH3-recognition (493-498), or ubiquitination sites on Kv1.3 (lysines 467, 476, 498) retained coimmunoprecipitation, while the latter prevented the reduction in channel density. A model is presented for which an atypical interaction outside the canonical PY motif may permit channel/ligase interaction to lead to protein degradation and reduced current density, which can involve Nedd4-2/Grb10 interactions to disrupt Kv1.3 loss of current density.

Prevalence of and risk factors for hypertension in urban and rural India: the ICMR-INDIAB study.

The aim of the study is to determine the prevalence of hypertension (HTN) and its risk factors in urban and rural India. In Phase I of the Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study, individuals aged ⩾20 years were surveyed using a stratified multistage sampling design, in three states (Tamil Nadu, Maharashtra and Jharkhand) and one union territory (Chandigarh) of India. Blood pressure was measured in all study subjects (n=14 059). HTN was defined as systolic blood pressure ⩾140 mm Hg, and/or DBP ⩾90 mm Hg and/or use of antihypertensive drugs. Overall age-standardized prevalence of HTN was 26.3% (self-reported: 5.5%; newly detected: 20.8%). Urban residents of Tamil Nadu, Jharkhand, Chandigarh and Maharashtra (31.5, 28.9, 30.7 and 28.1%) had significantly higher prevalence of HTN compared with rural residents (26.2, 21.7, 19.8 and 24.0%, respectively). Multivariate regression analysis showed that age, male gender, urban residence, generalized obesity, diabetes, physical inactivity and alcohol consumption were significantly associated with HTN. Salt intake ⩾6.5 g per day, showed significantly higher risk for HTN (odds ratio: 1.4, 95% confidence interval: 1.0-1.9, P=0.042) even after adjusting for confounding variables. In conclusion, prevalence of undiagnosed HTN is high in India and this calls for regular screening.

Knowledge and awareness of diabetes in urban and rural India: The Indian Council of Medical Research India Diabetes Study (Phase I): Indian Council of Medical Research India Diabetes 4.

BACKGROUND: Representative data on knowledge and awareness about diabetes is scarce in India and is extremely important to plan public health policies aimed at preventing and controlling diabetes. AIM: The aim of the following study is to assess awareness and knowledge about diabetes in the general population, as well as in individuals with diabetes in four selected regions of India. MATERIALS AND METHODS: The study subjects were drawn from a representative sample of four geographical regions of India, Chandigarh, Tamil Nadu, Jharkhand and Maharashtra representing North, South, East and West and covering a population of 213 million. A total of 16,607 individuals (5112 urban and 11,495 rural) aged ≥20 years were selected from 188 urban and 175 rural areas. Awareness of diabetes and knowledge of causative factors and complications of diabetes were assessed using an interviewer administered structured questionnaire in 14,274 individuals (response rate, 86.0%), which included 480 self-reported diabetic subjects. RESULTS: Only 43.2% (6160/14,274) of the overall study population had heard about a condition called diabetes. Overall urban residents had higher awareness rates (58.4%) compared to rural residents (36.8%) (P < 0.001). About 46.7% of males and 39.6% of females reported that they knew about a condition called diabetes (P < 0.001). Of the general population, 41.5% (5726/13,794) knew about a condition called diabetes. Among them, 80.7% (4620/5726) knew that the prevalence of diabetes was increasing, whereas among diabetic subjects, it was 93.0% (448/480). Among the general and diabetic population, 56.3% and 63.4% respectively, were aware that diabetes could be prevented. Regarding complications, 51.5% of the general population and 72.7% diabetic population knew that diabetes could affect other organs. Based on a composite knowledge score to assess knowledge among the general population, Tamil Nadu had the highest (31.7) and Jharkhand the lowest score (16.3). However among self-reported diabetic subjects, Maharashtra had the highest (70.1) and Tamil Nadu, the lowest score (56.5). CONCLUSION: Knowledge and awareness about diabetes in India, particularly in rural areas, is poor. This underscores the need for conducting large scale diabetes awareness and education programs.

In-vitro anti-inflammatory and mosquito larvicidal efficacy of nickel nanoparticles phytofabricated from aqueous leaf extracts of Aegle marmelos Correa.

In recent years there is a tremendous growth in the interdisciplinary world of nanotechnology across the globe and emergence of its potential applications remains as a big revolution to the industry. Fusion of green nanotechnology and medicine represents one of the major breakthroughs of modern science with the aim of developing nanomaterials for diagnosis, treatment, prevention of various diseases and overall improving health for the beneficial of mankind. In the present study phytofabrication of nickel nanoparticles (nickel NPs) was carried out by using indigenous Aegle marmelos Correa aqueous leaf extracts as a reducing, stabilizing and capping agents. Nickel NPs were characterized by UV-spectroscopy, FTIR, XRD, SEM, AFM and TGA studies. Phytosynthesis of nickel NPs was monitored both at room temperature (25°C) and at 60°C for 5h. The green synthesis of triangular shape nickel NPs phytofabricated from A. marmelos Correa aqueous leaf extracts having face centered cubic structure showing an average particle size of 80-100nm which is in consistent with the particle size calculated by XRD Scherer equation. We further explored and compared nickel NPs of A. marmelos Correa with crude leaf extracts of A. marmelos Correa for its in-vitro anti-inflammatory and mosquito larvicidal efficacy against three blood feeding parasites. The results obtained clearly gives an idea that nickel NPs of A. marmelos Correa (NiNPs of AmC) possess an enhanced anti-inflammatory and larvicidal activity when compared to crude leaf extracts of A. marmelos Correa.

Synthesis, spectral characterization and larvicidal activity of acridin-1(2H)-one analogues.

Acridin-1(2H)-one analogue of 7-chloro-3,4-dihydro-9-phenyl-2-[(pyridine-2yl) methylene] acridin-1(2H)-one, 5 was prepared by using 7-chloro-3,4-dihydro-9-phenylacridin-1(2H)-one, 3 and picolinaldehyde, 4 in the presence of KOH at room temperature. These compounds were characterized by analytical and spectral analyses. The purpose of the present study was to assess the efficacy of larvicidal and repellent activity of synthesized 7-chloro-3,4-dihydro-9-phenyl-acridin-1(2H)-one analogues such as compounds 3 and 5 against the early fourth instar larvae of filariasis vector, Culex quinquefasciatus and Japanese encephalitis vector, Culex gelidus (Diptera: Culicidae). The compound exhibited high larvicidal effects at 50mg/L against both the mosquitoes with LC(50) values of 25.02 mg/L (r(2)=0.998) and 26.40 mg/L (r(2)=0.988) against C. quinquefasciatus and C. gelidus, respectively. The 7-chloro-3,4-dihydro-9-phenyl-acridin-1(2H)-one analogues that are reported for the first time to our best of knowledge can be better explored for the control of mosquito population. This is an ideal ecofriendly approach for the control of Japanese encephalitis vectors, C. quinquefasciatus and C. gelidus.

Prevalence of diabetes, obesity, and metabolic syndrome in subjects with and without schizophrenia (CURES-104).

BACKGROUND: There are some reports that diabetes and metabolic syndrome (MS) are more prevalent among schizophrenia patients. However, there are very few studies in India which have estimated the prevalence of diabetes and MS in schizophrenia patients. AIMS: The aim of this study was to determine the prevalence of diabetes, obesity, and MS in subjects with and without schizophrenia. SETTINGS AND DESIGN: This case control study comprised of "cases" i.e. subjects with schizophrenia recruited from a schizophrenia centre at Chennai and "controls" i.e. healthy age- and gender-matched subjects without psychiatric illness selected from an ongoing epidemiological study in Chennai in a 1:4 ratio of cases: Controls. MATERIALS AND METHODS: Fasting plasma glucose and serum lipids were estimated for all subjects. Anthropometric measures including height, weight, and waist circumference were assessed. Diabetes and impaired fasting glucose (IFG) were defined using American Diabetes Association criteria. STATISTICAL ANALYSIS: One-way ANOVA or student's "t" test was used to compare continuous variables and Chi-square test to compare proportion between two groups. RESULTS: The study group comprised of 655 subjects, 131 with schizophrenia and a control group of 524 subjects without schizophrenia. The prevalence of the diabetes, IFG, abdominal obesity and MS were significantly higher among subjects with schizophrenia compared to those without schizophrenia-diabetes (15.3% vs. 7.3%, P=0.003), IFG (31.3% vs. 8.6%, P<0.001), abdominal obesity (59.2% vs. 44.7%, P<0.001), and MS (34.4% vs. 24%, P=0.014). CONCLUSION: In subjects with schizophrenia, the prevalence of diabetes, IFG, abdominal obesity, and MS is significantly higher than in those without schizophrenia.

Prevalence of diabetes and prediabetes (impaired fasting glucose and/or impaired glucose tolerance) in urban and rural India: phase I results of the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study.

AIMS/HYPOTHESIS: This study reports the results of the first phase of a national study to determine the prevalence of diabetes and prediabetes (impaired fasting glucose and/or impaired glucose tolerance) in India. METHODS: A total of 363 primary sampling units (188 urban, 175 rural), in three states (Tamilnadu, Maharashtra and Jharkhand) and one union territory (Chandigarh) of India were sampled using a stratified multistage sampling design to survey individuals aged ≥ 20 years. The prevalence rates of diabetes and prediabetes were assessed by measurement of fasting and 2 h post glucose load capillary blood glucose. RESULTS: Of the 16,607 individuals selected for the study, 14,277 (86%) participated, of whom 13,055 gave blood samples. The weighted prevalence of diabetes (both known and newly diagnosed) was 10.4% in Tamilnadu, 8.4% in Maharashtra, 5.3% in Jharkhand, and 13.6% in Chandigarh. The prevalences of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) were 8.3%, 12.8%, 8.1% and 14.6% respectively. Multiple logistic regression analysis showed that age, male sex, family history of diabetes, urban residence, abdominal obesity, generalised obesity, hypertension and income status were significantly associated with diabetes. Significant risk factors for prediabetes were age, family history of diabetes, abdominal obesity, hypertension and income status. CONCLUSIONS/INTERPRETATIONS: We estimate that, in 2011, Maharashtra will have 6 million individuals with diabetes and 9.2 million with prediabetes, Tamilnadu will have 4.8 million with diabetes and 3.9 million with prediabetes, Jharkhand will have 0.96 million with diabetes and 1.5 million with prediabetes, and Chandigarh will have 0.12 million with diabetes and 0.13 million with prediabetes. Projections for the whole of India would be 62.4 million people with diabetes and 77.2 million people with prediabetes.

2,4-Dichloro-7,8-dimethyl-quinoline.

There are two independent mol-ecules in the asymmetric unit of the title compound, C(11)H(9)Cl(2)N, both of which are essentially planar [maximum deviations of 0.072 (5) and 0.072 (7) Å]. In the crystal structure, weak π-π stacking inter-actions [centroid-centroid distances = 3.791 (3) Šand 3.855 (3) Å] link pairs of mol-ecules.

Measurement of human immunodeficiency virus type 1 preintegration transcription by using Rev-dependent Rev-CEM cells reveals a sizable transcribing DNA population comparable to that from proviral templates.

Preintegration transcription is an early process in human immunodeficiency virus type 1 infection and has been suggested to occur at a low level. The templates have also been suggested to represent a small population of nonintegrated viral DNA, particularly the two-long-terminal-repeat (2-LTR) circles. However, these determinations were made by either using PCR amplification of viral transcripts in bulk cell populations or utilizing the LTR-driving reporter cells that measure the synthesis of Tat. The intrinsic leakiness of LTR often makes the measurement of low-level viral transcription inaccurate. Since preintegration transcription also generates Rev, to eliminate the nonspecificity associated with the use of LTR alone we have developed a novel Rev-dependent indicator cell, Rev-CEM, to measure preintegration transcription based on the amount of Rev generated. In this report, using Rev-CEM cells, we demonstrate that preintegration transcription occurs on a much larger scale than expected. The transcribing population derived from nonintegrated viral DNA was comparable (at approximately 70%) to that derived from provirus in a productive viral replication cycle. Nevertheless, each nonintegrated viral DNA template exhibited a significant reduction in the level of transcriptional activity in the absence of integration. We also performed flow cytometry sorting of infected cells to identify viral templates. Surprisingly, our results suggest that the majority of 2-LTR circles are not active in directing transcription. It is likely that the nonintegrated templates are from the predominant DNA species, such as the full-length, linear DNA. Our results also suggest that a nonintegrating lentiviral vector can be as effective as an integrating vector in directing gene expression in nondividing cells, with the proper choice of an internal promoter.

Large cryptic internal sequence repeats in protein structures from Homo sapiens.

Amino acid sequences are known to constantly mutate and diverge unless there is a limiting condition that makes such a change deleterious. However, closer examination of the sequence and structure reveals that a few large, cryptic repeats are nevertheless sequentially conserved. This leads to the question of why only certain repeats are conserved at the sequence level. It would be interesting to find out if these sequences maintain their conservation at the three-dimensional structure level. They can play an active role in protein and nucleotide stability, thus not only ensuring proper functioning but also potentiating malfunction and disease. Therefore,insights into any aspect of the repeats - be it structure, function or evolution - would prove to be of some importance. This study aims to address the relationship between protein sequence and its three-dimensional structure, by examining if large cryptic sequence repeats have the same structure.

2-Chloro-6-methyl-quinoline-3-carbaldehyde.

The quinolinyl fused-ring of the title compound, C(11)H(8)ClNO, is almost planar (r.m.s. deviation = 0.013 Å); the formyl group is slightly bent out of the plane of the fused ring system [C-C-C-O torsion angle = 13.5 (4)°].

2-Chloro-7,8-dimethyl-quinoline-3-carbaldehyde.

All the non-H atoms of the title compound, C(12)H(10)ClNO, lie on a crystallographic mirror plane orientated perpendicular to the crystallographic b axis.

2-Chloro-quinoline-3-carbaldehyde.

The quinolinyl fused ring system of the title compound, C(10)H(6)ClNO, is planar (r.m.s. deviation = 0.018 Å); the formyl group is slightly bent out of the plane of the fused ring system [C-C-C-O torsion angle = 8.2 (3)°].

2-Chloro-benzo[h]quinoline-3-carbaldehyde.

The benzo[h]quinolinyl fused-ring of the title compound, C(14)H(8)ClNO, is planar (r.m.s. deviation = 0.016 Å); the formyl group is slightly bent out of the plane [the C-C-C-O torsion angle is 10.7 (4)°].

2-Chloro-8-methoxy-quinoline-3-carbaldehyde.

In the title compound, C(11)H(8)ClNO(2), the quinoline fused-ring system is almost planar (r.m.s. deviation = 0.020 Å). The formyl group is slightly bent out of the quinoline plane [deviation of the O atom = 0.371 (2) Å].

2-Chloro-7-methyl-quinoline-3-carbaldehyde.

The quinoline fused-ring system of the title compound, C(11)H(8)ClNO, is planar (r.m.s. deviation = 0.007 Å); the formyl group is bent slightly out of the plane [C-C-C-O torsion angles = -9.6 (5) and 170.4 (3)°].

2-Chloro-8-methyl-quinoline-3-carbaldehyde.

The quinoline fused-ring system of the title compound, C(11)H(8)ClNO, is planar (r.m.s. deviation = 0.005 Å); the formyl group is slightly bent out of the plane [C-C-C-O1 torsion angles = 8.8 (7) and -172.8 (4)°].

2-Chloro-6-methoxy-quinoline-3-carbaldehyde.

The quinoline fused-ring system of the title compound, C(11)H(8)ClNO(2), is planar (r.m.s. deviation = 0.0095 Å); the formyl group is slightly bent out of this plane [C-C-C-O torsion angles = -2.4 (3) and 175.9 (2)°].