Selective, Ultra-Sensitive, and Rapid Detection of Serotonin by Optimized ZnO Nanorod FET Biosensor.

BACKGROUND: Fluctuation in serotonin (5-HT) level is an essential manifestation of several neurological disorders. In view of such importance, it is necessary to monitor the levels of 5-HT with good sensitivity, selectivity, affordability and low response time. Zinc oxide (ZnO) based field effect transistors (FET) with attributes like minimized noise levels and large on-off ratio are regarded as emerging high performance biosensor platforms. However, their response is significantly non-linear and there has been no appreciable endeavor for improving the non-linearity. METHOD: In this paper, we have introduced embedded gate electrode encompassing the channel of the FET which improves the uniformity in electric field line distribution through the electrolyte and proportionately enhances the capture of target biomolecule at ultra-low concentrations, thereby increasing the linearity. Further, we have incorporated the optimized parameters of ZnO nanorods reported previously, for rapid and selective detection of 5-HT. RESULTS: It has been observed that the fabricated ZnO FET biosensor lowers the detection limit down to 0.1fM which is at least one order of magnitude lower than the existing reports. The sensor also has wide linear range from 0.1fM to 1nM with a detection time of about 20 minutes. CONCLUSION: The proposed zinc oxide nanorod-based sensor can be used as an excellent tool for future diagnosis of neurological disorders.

Label free, electric field mediated ultrasensitive electrochemical point-of-care device for CEA detection.

Developing point-of-care (PoC) diagnostic platforms for carcinoembryonic antigen detection is essential. However, thefew implementations of transferring the signal amplification strategies in electrochemical sensing on paper-based platforms are not satisfactory in terms of detection limit (LOD). In the quest for pushing down LOD, majority of the research has been targeted towards development of improved nanostructured substrates for entrapping more analyte molecules and augmenting the electron transfer rate to the working electrode. But, such approaches have reached saturation. This paper focuses on enhancing the mass transport of the analyte towards the sensor surface through the application of an electric field, in graphene-ZnO nanorods heterostructure. These hybrid nanostructures have been deposited on flexible polyethylene terephthalate substrates with screen printed electrodes for PoC application. The ZnO nanorods have been functionalized with aptamers and the working sensor has been integrated with smartphone interfaced indigenously developed low cost potentiostat. The performance of the system, requiring only 50 µl analyte has been evaluated using electrochemical impedance spectroscopy and validated against commercially available ELISA kit. Limit of detection of 1 fg/ml in human serum with 6.5% coefficient of variation has been demonstrated, which is more than three orders of magnitude lower than the existing attempts on PoC device.

Massive intracerebral hemorrhage in an amphetamine addict.

A case of massive intracerebral hemorrhage, a rare but often fatal complication of amphetamine abuse, is described along with the review of the literature. There has been resurgence in the abuse of amphetamine. Amphetamine or other illicit drug abuse should be considered in young patients with cerebrovascular events.

Patellar stress fracture: a complication of knee joint arthroplasty without patellar resurfacing.

A case of patellar stress fracture after total knee arthroplasty in a man with gout and previous osteonecrosis of the tali is reported. The combination of fat pad excision and lateral release causing disruption to the patellar blood supply during primary total knee arthroplasty resulted in the development of a patellar fracture. Avascular necrosis, caused by gout, may form part of the pathogenesis.

Comparative analysis of chicken Hoxb-4 regulation in transgenic mice.

We cloned the chicken Hoxb-4 gene and performed in situ analysis to investigate conservation in patterns of expression between the chicken and mouse. The anterior boundaries of expression for both genes in segmented tissues, such as the hindbrain and paraxial mesoderm, map to the same rhombomere (r) (r6/r7) and somite (s) (s6/s7) limits, showing a direct correlation between expression of a specific Hox gene and patterning identical axial structures in both species. Given this similarity in expression we have tested the functional activity of cis-regulatory regions from the chicken Hoxb-4 gene in transgenic mice to identify and map components conserved between the species. We identified enhancers which contain conserved blocks of sequence identity and which are necessary to mediate mesodermal and neural restricted patterns of expression. However, only the neural enhancer directs the proper anterior boundary of expression (r6/r7), indicating that only a subset of the underlying molecular components regulating Hoxb-4 expression are functionally conserved between species.

Detecting conserved regulatory elements with the model genome of the Japanese puffer fish, Fugu rubripes.

Comparative vertebrate genome sequencing offers a powerful method for detecting conserved regulatory sequences. We propose that the compact genome of the teleost Fugu rubripes is well suited for this purpose. The evolutionary distance of teleosts from other vertebrates offers the maximum stringency for such evolutionary comparisons. To illustrate the comparative genome approach for F. rubripes, we use sequence comparisons between mouse and Fugu Hoxb-4 noncoding regions to identify conserved sequence blocks. We have used two approaches to test the function of these conserved blocks. In the first, homologous sequences were deleted from a mouse enhancer, resulting in a tissue-specific loss of activity when assayed in transgenic mice. In the second approach, Fugu DNA sequences showing homology to mouse sequences were tested for enhancer activity in transgenic mice. This strategy identified a neural element that mediates a subset of Hoxb-4 expression that is conserved between mammals and teleosts. The comparison of noncoding vertebrate sequences with those of Fugu, coupled to a transgenic bioassay, represents a general approach suitable for many genome projects.

Characterisation of the murine Hox-3.3 gene and its promoter.

The murine Hox-3.3 homeobox containing gene and its Xenopus homologue (XlHbox 1) produce two embryonic transcripts from two distinct promoters located approximately 9 kb apart. In order to begin to characterise one of these promoter regions (PRII), we have sequenced 3 kb of DNA immediately upstream of the transcription start site of the PRII transcript and analyzed the sequence for sequences known to bind transcription factors. Within this region are located a number of sequences that match known cis-elements. We have analysed the ability of two of these sequences that match to the Drosophila hunchback and Antennapedia/fushi-tarazu consensus binding sequences to specifically bind proteins extracted from embryos and from adult tissues. Using gel retention assays with oligonucleotides derived from these sequences, we show that both sequences specifically bind proteins present in extracts of mouse embryos and some, but not all extracts of various adult tissues. Protein binding cannot, however, be correlated with the known spatial domains of Hox-3.3 expression, suggesting that binding to these sequences is not simply related to activation of Hox-3.3 expression. A two base pair change in the most conserved region of the hunchback-like binding sequence completely abolishes protein binding. The presence of these highly conserved cis-acting elements that are known to be involved in regulation of the hunchback, even-skipped and engrailed genes in Drosophila suggests that these sequences may also be involved in the regulation of expression of Hox-3.3 and furthermore that regulation may in part at least involve binding of hunchback-like proteins (i.e. zinc-finger proteins) and Antennapedia-like homeobox-containing proteins.

Biochemical studies following ovulation induction with clomiphene citrate and human menopausal gonadotropin in infertile Indian women.

Biochemical studies were done in 65 anovulatory women before and following induction of ovulation with ethinyl estradiol/clomiphene citrate/human chorionic gonadotropin and also clomiphene citrate/human menopausal gonadotropin/human chorionic gonadotropin to determine the metabolic adverse effects, if any, of such therapy. Significant increases occurred in lipids and lipoprotein levels, while minor changes were seen in liver function enzymes and fasting blood sugar. Sialic acid decreased significantly after therapy in both the regimens, and both induction therapies seem to be free of adverse metabolic effects of hormones. On comparison with normal ovulatory women, this study suggests that some of the biochemical parameters can serve as reliable indicators of ensuing ovulation.

Alterations in blood sugar, protein, and lipid levels in Indian women by norethisterone enanthate.

Fasting levels of sugar, protein, and lipids, namely, cholesterol, triglyceride, and phospholipid, were determined in the blood of 150 women taking an injectable contraceptive, norethisterone enanthate, 200 mg every 60 days for 24 months. Triglyceride and cholesterol showed a statistically significant decrease from 10 and 16 months of use; however, both values returned to control level after use for 24 months. Serum phospholipids and total protein did not show significant changes, while the blood sugar level increased significantly from 12 months onwards and remained elevated (P less than .001) up to the end of the trial period.

PIP: 150 healthy female subjects aged 18-35 and ranging in parity from 1 to 3 were tested to determine the fasting levels of sugar, protein and lipids, particularly cholesterol, triglyceride and phospholipid. All of the women were receiving injections of the contraceptive norethisterone enanthate: 200 mg every 60 days for 2 years. The samples of blood were obtained from an antecubital vein before an injection of norethisterone enanthate (NET-EN). A substantial decline in serum triglyceride level was evident after 8 months. Serum cholesterol level declined after 14 months, but resumed its normal level after continued use. Changes in the phospholipid level were minor. Blood sugar increased substantially; however, the total protein level remained relatively unchanged. A tendency to decrease total cholesterol and triglyceride levels was observed. Levels returned to normal, however, after 2 years. In contrast to past studies, the fasting blood sugar level rose steadily. Although the rise in blood sugar level was not sufficient to cause concern, caution should still be practiced when administering NET-EN.

Effect of norethisterone enanthate on the blood count and endometrial histology of Indian women.

Endometrial histology and the haematological indices were studied in women receiving 200 mg of norethisterone enanthate (NET-EN) at 60-day intervals for 24 months as a method of contraception. Significant elevations occurred in the haemoglobin concentration and red blood cell counts during one year of therapy, while eosinophil counts showed a transient increase at 4 months of trial. The changes in the haematological indices seem to be due to stimulation of the erythropoietic system by NET-EN and may also be attributable to diminished blood loss due to amenorrhoea during the course of therapy. The endometrial histology revealed proliferative glands at 2 months which turned quiescent at 6-12 months of NET-EN therapy. Long-term use of 18 months showed atrophic changes with few glands, narrow lumina and stromal oedema.

Studies on some enzymes and sialic acid during progestational contraceptive therapy.

Injectable progestogen, norethisterone enanthate (NET-EN, 200 mg/ml at 60-day intervals), was administered to one-hundred-fifty women for two years as a method of contraception. Blood levels of acid phosphatase (ACP), alkaline phosphatase (AP), glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), acetylcholinesterase (AChE) and sialic acid were determined in all the subjects to ascertain whether NET-EN therapy causes any adverse metabolic effect or damage to the functional status of the liver. NET-EN contraception did not alter the liver function enzymes, but there is a significant increase (P less than 0.001) in AChE activity after two years. Serum sialic acid level showed a transient increase up to one year, which however returned to control level later. The mechanism responsible for these changes and whether the rise in sialic acid and AChE activity are related to any pathological condition remain unclear at this stage.

PIP: Injectable progestogen, norethisterone enanthate (NET-EN, 200 mg/ml at 60 day intervals), was administered to 150 women for 2 years as their method of contraception. Blood levels of acid phosphatase, alkaline phosphatase, glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, acetylcholinesterase (AChe), sialic acid were determined in all subjects to ascertain whether NET-EN therapy causes any adverse metabolic effect or damage to the functional status of the liver. NET-EN contraception did not alter the liver function enzymes but there is a significant increase (P0.001) in AChE activity after 2 years. Serum sialic acid level showed a transient increase up to 1 year, which however returned to control level later. The mechanism responsible for these changes and whether the rise in sialic acid and AChE activity are related to any pathological condition remain unclear at this stage.

Clinical trial of a long-acting injectable contraceptive: NET-EN.

Injectable progestogen, norethisterone enanthate (NET-EN, 200 mg/ml) was administered to 122 women at 2 month intervals for more than 1 year. Only a minority of women had consistently normal cycles. Most women experienced some menstrual irregularities: 57% of users experienced irregular bleeding, 32% developed amenorrhea, while only 11% showed regular cyclic bleeding. Important nonmenstrual side effects were weakness and abdominal pain. No appreciable changes in body weight and blood pressure were recorded.

L-ascorbic acid synthesis in birds: phylogenetic trend.

The ability of several species of birds to synthesize L-ascorbic acid is correlated with their phylogeny. In the more primitive species, synthesis of L-ascorbic acid occurs in the kidney. Among the highly evolved passeriform species, kidney and liver can synthesize L-ascorbic acid in some, whereas in others synthesis occurs in the liver. In still others, the capacity for the synthesis of L-ascorbic acid is apparently lost. The pattern of evolution of the ascorbic acid pathway among birds is thus similar to that among mammals.