Evaluation of cilnidipine-loaded self-micro-emulsifying drug delivery system (SMEDDS) by quantification of comparative pharmacokinetic parameters using validated LC-ESI-MS/MS bioanalytical method and pharmacodynamic assessment.

OBJECTIVE: Regardless of having desired therapeutic properties many of the recently approved drugs are removed from the developmental pipeline for their clinical use due to low solubility and permeability. Conventional dosage forms are found relatively unsuitable for achieving desired pharmacokinetic and pharmacodynamics profiles. Cilnidipine is 1,4 dihydropyridine derivative calcium channel blocker used for the treatment of hypertension. METHOD: The aim and objective of this study was to develop a precise and significant method in LC-MS/MS for quantification of pharmacokinetic parameters of a cilnidipine-loaded self-micro-emulsifying drug delivery system in rat plasma and simultaneously assessed pharmacodynamic characters in comparison with the marketed cilnidipine tablet. Another potential aim of this study is to reduce the dose of the drug in order to counter the dose-dependent toxicities related to chronic use. In the present study, the parent and product ion of cilnidipine was m/z 491.3\237.1. RESULT: The plasma was extracted by protein precipitation technique. The calibration standard concentrations were 1.875, 3.75, 7.50, 15.00, 30.00, 60.00ng/mL and LLOQ, low-quality control, middle-quality control and high-quality control were 1.87, 5.62, 22.50, 45.00ng/mL, respectively. The mobile phase composition was 0.1% formic acid in Milli Q water with 10mM Ammonium acetate as an aqueous solvent and 0.1% formic acid in methanol as an organic solvent. Following oral administration of optimized formulation Cmax (peak plasma concentration) was achieved 21.02±3.17ng/mL at 0.866±0.11h (Tmax), whereas in the case of marketed tablet Cmax (peak plasma concentration) was achieved 10.16±0.89ng/mL at 0.93±0.11h (Tmax). DISCUSSION: The in-vivo characterizations of the optimized SMEDDS showed significantly better pharmacokinetic parameters in Wistar rats and showed almost 2.4 times enhanced relative bioavailability as compared to the marketed tablet of cilnidipine which was observed to be correlating to our findings with noninvasive blood pressure parameter of Wistar rats.

Characterization and removal of microplastics in a sewage treatment plant from urban Nagpur, India.

Sewage treatment plant (STP) acts as a potential source of microplastic contamination in the environment. The presence of microplastics in the sewage treatment plant is reported over the globe in varying concentrations. Hence, the current study is intended to evaluate the presence and abundance of microplastics occurring in sewage treatment plants in India. The samples were processed through digestion and density separation, followed by microscopic and polymer identification through Fourier transform infrared spectroscopy. Also, different wastewater parameters were studied to analyze their influence. High microplastic concentrations were detected in the influent (1860 ± 265 MPs/L), which reduced by > 90%, to around 148 ± 51 MPs/L in the effluent. The concentration of microplastics in sewage sludge was 830 MPs/kg. The prominent plastic types identified include low-density polyethylene, polypropylene, polyurethane, polyvinyl chloride, and rayon. The smaller particles prevail in the effluent, releasing around 30 billion particles per day to the environment. This suggests that the current STP is efficient in removing the majority of the particles, but considerations are needed to avoid the ecological risks associated.

Adriaan van den Spiegel (1578-1625): anatomist, physician, and botanist.

Adriaan van den Spiegel (1578-1625) was a Flemish anatomist and physician. He was one of the most prominent anatomists at the University of Padua during the 17th century and became professor of anatomy and surgery there in 1619. He was privileged to have two of the most accomplished anatomists of that period, Fabricius ab Aquapendente and Iulius Casserius, as his teachers. His anatomical works were published after his death by his pupil Bucretius and his son-in-law Liberalis Crema, with illustrations procured from Casserius's unpublished anatomical atlas. He contributed significantly to establishing basic morphological facts about the developing embryo in his text De formato foetu liber singularis. In his book De humani corporis fabrica libri decem, Spiegel's lobe (caudate lobe) of the liver and the linea semilunaris (Spiegel's line) on the lateral side of the rectus abdominis muscle were described for the first time. Subsequently, Spigelian aponeurosis (between the lateral margin of the rectus abdominis and the linea semilunaris) and Spigelian hernia (lateral ventral hernia) were named after him. He was a renowned physician in his time and was the first to give a detailed description of malaria. He made significant contributions as a botanist: the genus Spigelia, which has six species, is named after him.

Variable-Barrier Quantum Coulomb Blockade Effect in Nanoscale Transistors.

Current-voltage characteristics of a quantum dot in double-barrier configuration, as formed in the nanoscale channel of silicon transistors, were analyzed both experimentally and theoretically. Single electron transistors (SET) made in a SOI-FET configuration using silicon quantum dot as well as phosphorus donor quantum dots were experimentally investigated. These devices exhibited a quantum Coulomb blockade phenomenon along with a detectable effect of variable tunnel barriers. To replicate the experimental results, we developed a generalized formalism for the tunnel-barrier dependent quantum Coulomb blockade by modifying the rate-equation approach. We qualitatively replicate the experimental results with numerical calculation using this formalism for two and three energy levels participated in the tunneling transport. The new formalism supports the features of most of the small-scaled SET devices.

Cytological, Histochemical, and Ultrastructural Study of the Human Fetal Spleen of Various Gestational Age With Future Implications in Splenic Transplantation: An Anatomical Perspective.

PURPOSE: The spleen is a fist-sized largest lymphoid organ located in the left hypochondrium. It has a unique location, embryological and histological structure that differs significantly from other lymphoid organs. The present work was undertaken to study the microscopic and ultramicroscopic histogenesis patterns of the spleen in relation to gestational age. METHODS: The splenic tissue of nine aborted fetuses of various gestational ages was studied. For cytology study, special stains like Masson's trichrome, Periodic Acid-Schiff, and Reticulin were used; immunohistochemical staining was performed with triple antibodies (C-myc, Ki-67, and Ber-H2); and for ultrastructure study, aluminum mounted specimens coated with gold and argon gas were observed under scanning electron microscopy (SEM). RESULTS: Microscopy and immunohistochemistry showed the developmental changes in the spleen from the emergence of the primordium to the end of the embryonic period in all stages of fetogenesis. The spleen primordium of a fetus at the developmental stage of the primary vascular reticulum was seen in the first trimester fetuses. The primordium is comprised mainly of mesenchymal tissue; numerous lymphocytes invading the area surrounding the central artery forming the periarterial lymphoid sheaths (PALS) were seen surrounded by venous sinuses in the early second trimester fetuses. CONCLUSION: The organizational changes in the reticuloendothelial system and microstructure of the spleen during fetogenesis are very crucial to achieving adult morphology in the future. Histogenesis of the fetal spleen follows a multistep process depending upon the gestational age. Any deviation from normalcy may lead to structural and functional abnormality later in life.

Attenuation of haemodynamic responses to laryngoscopy and endotracheal intubation with dexmedetomidine: A comparison between intravenous and intranasal route.

BACKGROUND AND AIMS: Haemodynamic changes during endotracheal intubation are major concerns in general anaesthesia This study compared the efficacy of intranasal and intravenous dexmedetomidine (DEX) to attenuate the stress response of laryngoscopy and endotracheal intubation. METHODS: In this prospective, randomised, double-blinded study, 70 adults were divided into two groups [Group DIV(n=35) and Group DIN(n=35)]. DIV group received intravenous dexmedetomidine (DEX) infusion (0.5 µg/kg) over 40 min and DIN group received intranasal dexmedetomidine (1 µg/kg) 40 min before induction. The primary objective was the comparison the mean arterial pressure (MAP) between two groups from 40 min before induction at every 10 min intervals till induction of anaesthesia, at the time of intubation, thereafter every 1 min interval till 5 min, at 7 min and 10 min after intubation. The secondary outcomes were comparison of heart rate, systolic and diastolic blood pressure along with sedation and other adverse effects. Statistical analysis was with Statistica 6.0 and Graph Pad prism version 5. RESULTS: In both the groups, all the haemodynamic parameters were maintained within (20% of baseline values) throughout the study period. There was no statistically significant difference in MAP between two groups (P>0.05). Preoperative sedation score was significantly higher in the DIV group than the DIN group (P = 0.014). CONCLUSION: Like IV DEX, intranasal DEX can also attenuate the haemodynamic stress responses of laryngoscopy and endotracheal intubation without significant differences in MAP between two groups.

Simultaneous Determination and Quantitation of Diosmetin and Hesperetin in Human Plasma by Liquid Chromatographic Mass Spectrometry With an Application to Pharmacokinetic Studies.

Among the secondary metabolites which are widely distributed in plants and foods in plant origin flavonoids is important one. Flavonoids have antioxidant activities as free radical scavenging action. They also have anti-inflammatory, antiulcer and anti-carcinogenic activities. Diosmin and hesperidin, the metabolites of which are diosmetin and hesperitin respectively are considered in the present study. Diosmetin has anticancer, antioxidant and blood lipid lowering activities. It also enhances venous tone and microcirculation and by reducing systemic oxidative stress it protects capillaries. Hesperitin also has antioxidant, anti-inflammatory, blood lipid and cholesterol lowering, anti-carcinogenic activities. In the present study efforts were given to develop and validate a bioanalytical method for simultaneous estimation of diosmetin and hesperitin in human plasma by liquid chromatography electron spray ionization mass spectrometry with an application to the analysis of plasma samples obtained from the comparative pharmacokinetic studies on healthy human volunteers under the framework of bioequivalence study. The developed method for simultaneous determination and quantification of diosmetin and hesperitin in human plasma was validated as per the US-FDA guidelines. The validation parameters found within the specified regulatory limit, hence acceptable. The present method also has a short run time (6.0 min) and easy extraction process. The developed method was found to be simple, specific, highly selective, sensitive and reproducible. This was applied for the analysis of the volunteer plasma samples. On the basis of comparison of the AUC0-t, the relative bioavailability of the test preparation was found 100.94 and 95.09% for diosmetin and hesperitin respectively of that of the reference preparation.

An anatomical study of wormian bones from the eastern part of India: is genetic influence a primary determinant of their morphogenesis?

Over the years a number of investigators have analysed the morphology of wormian bones in different population groups across the world. There have been significant variations between findings reported in these studies, and this has prompted researchers to focus on the influence of genetic factors on the morphology of these bones. In the light of the above observation, we considered it justified to conduct anatomical studies on wormian bones in different population groups; hence, we undertook the present study to look into the morphological details of these bones among a population in the eastern part of India. We observed a total of 120 adult dry human skulls of unknown age and sex, and noted the anatomical details of wormian bones when present. It was observed that wormian bones were present in 45 % of skulls, and that 30 % of skulls had more than one wormian bone. We also found that 2.5 % of the skulls had ten or more wormian bones, which is considered as pathognomonic. Maximum incidence (53.33 %) was observed at the lambdoid suture and minimum incidence at the bregma and metopic suture (0.61 % in each case). We noted a high incidence (21.21 %) of Inca bone/lambdoid ossicle, and bilaterally symmetrical wormian bones were present in 12.5 % study skulls. There were statistically significant (P < 0.05) variations between the findings of the present study and values reported in previous studies conducted in other regions of India and different parts of the world. Our observations favour the view that genetic influence primarily determines the morphology of wormian bones.

Low-power, low-rate ultrasonic communications system transmitting axially along a cylindrical pipe using transverse waves.

Acoustic-electric channels have been used in the recent past to send power and data through thin metallic barriers. Acoustic-electric channels formed along a structure which are highly attenuative and nonreverberant could have potential applications in aerospace, nuclear, and oil industries, among others. This work considers data transmission along the length of a cylindrical pipe both when in air and when filled and immersed in water using shear waves of transverse polarity. To combat the effects of frequency selectivity and to address the available power constraints, a simple modulation scheme using noncoherent demodulation is employed for data transmission: chirp-on-off keying (Chirp-OOK). The wideband nature of the chirp waveform provides resilience against nulls in the channel response while making it possible to implement a simple noncoherent energy detector. Monte Carlo simulation results using measured channel responses suggest that the bit error rate performance of the scheme matches quite closely with the theoretical results. The energy detector performance is independent of the type of the channel used as long as intersymbol-interference is negligible and same received Eb/N0 is maintained. A low-power prototype hardware system was implemented using microcontrollers, commercial ICs, and custom circuits. Successful data transmission was achieved across the 4.8 m length of pipe (in air and water) for a data rate of 100 bps using approximately 5 mW of transmit power.

Avian scavengers and the threat from veterinary pharmaceuticals.

Veterinary use of the non-steroidal anti-inflammatory drug diclofenac on domesticated ungulates caused populations of resident Gyps vultures in the Indian sub-continent to collapse. The birds died when they fed on carrion from treated animals. Veterinary diclofenac was banned in 2006 and meloxicam was advocated as a 'vulture-safe' alternative. We examine the effectiveness of the 2006 ban, whether meloxicam has replaced diclofenac, and the impact of these changes on vultures. Drug residue data from liver samples collected from ungulate carcasses in India since 2004 demonstrate that the prevalence of diclofenac in carcasses in 2009 was half of that before the ban and meloxicam prevalence increased by 44%. The expected vulture death rate from diclofenac per meal in 2009 was one-third of that before the ban. Surveys at veterinary clinics show that diclofenac use in India began in 1994, coinciding with the onset of rapid Gyps declines ascertained from measured rates of declines. Our study shows that one pharmaceutical product has had a devastating impact on Asia's vultures. Large-scale research and survey were needed to detect, diagnose and quantify the problem and measure the response to remedial actions. Given these difficulties, other effects of pharmaceuticals in the environment may remain undetected.

Tarlov cysts: a report of two cases.

Perineural cysts are common and usually detected incidentally during magnetic resonance imaging of the lumbosacral spine. Treatment is indicated only when the cyst is symptomatic. We report one such patients presented with cauda equina syndrome and another with low back pain with claudication. They underwent excision and duraplasty; both motor and sensory fibres were carefully separated from the cyst wall using a nerve root retractor and penfield. There was no nerve root damage or neural deficit. Symptoms were relieved postoperatively.

Massive tubercular pseudo-tumor of the thigh: a case report.

Psoas abscess in cases of tuberculosis originates from the primary lesion in the lower dorsal or the lumbar spine. From the spinal origin of the Psoas muscle, this abscess tracks down its sheath and may be palpable in the iliac fossa, in the lumbar triangle, in the upper part of thigh below the inguinal ligament. We present a rare case, where patient presented with thigh swelling, which on first look gave an impression of a malignant origin. But subsequent investigation revealed it to be one of tuberculous origin, and that to, tracking down of a Psoas abscess. According to best of our knowledge, there has been no reported case of a Psoas abscess tracking down to the thigh and knee and mimicking a tumour.

Effectiveness of action in India to reduce exposure of Gyps vultures to the toxic veterinary drug diclofenac.

Contamination of their carrion food supply with the non-steroidal anti-inflammatory drug diclofenac has caused rapid population declines across the Indian subcontinent of three species of Gyps vultures endemic to South Asia. The governments of India, Pakistan and Nepal took action in 2006 to prevent the veterinary use of diclofenac on domesticated livestock, the route by which contamination occurs. We analyse data from three surveys of the prevalence and concentration of diclofenac residues in carcasses of domesticated ungulates in India, carried out before and after the implementation of a ban on veterinary use. There was little change in the prevalence and concentration of diclofenac between a survey before the ban and one conducted soon after its implementation, with the percentage of carcasses containing diclofenac in these surveys estimated at 10.8 and 10.7%, respectively. However, both the prevalence and concentration of diclofenac had fallen markedly 7-31 months after the implementation of the ban, with the true prevalence in this third survey estimated at 6.5%. Modelling of the impact of this reduction in diclofenac on the expected rate of decline of the oriental white-backed vulture (Gyps bengalensis) in India indicates that the decline rate has decreased to 40% of the rate before the ban, but is still likely to be rapid (about 18% year(-1)). Hence, further efforts to remove diclofenac from vulture food are still needed if the future recovery or successful reintroduction of vultures is to be feasible.