Downregulation of thromboxane A2 and angiotensin II type 1 receptors associated with aging-related decrease in internal anal sphincter tone.

Aging-associated decrease in internal anal sphincter (IAS) tone (AADI) is a major contributor in the rectoanal incontinence (RI). To determine the pathogenesis of AADI, we investigated the effect of aging on GPCR activation and related downstream signaling. We particularly investigated two GPCRs that characterize IAS smooth muscle cells (SMCs): thromboxane A 2 and angiotensin II type 1. Two groups of Fischer 344 rats (6-month-old [young group] and 26-month-old [old group]) were employed to determine the GPCR function by isometric contraction, the expressions of GPCRs, and their downstream regulatory signaling proteins (regulator of G-protein signaling 2, RGS2; GPCR Kinase 5, GRK5; and β-arrestin, Arrb2) using RT-PCR, qPCR, and western blot analyses. We used reversible biotinylation to monitor the GPCR trafficking using SMCs. Aging selectively attenuated thromboxane A 2 and Ang II-induced IAS contraction. RT-PCR, qPCR, and WB data revealed a significant decrease in the expressions of the GPCRs and increase in the expression of RGS2, GRK5, and Arrb2. The increased GPCR internalization and decreased recycling under aging were validated by reversible biotinylation. We conclude that downregulation of GPCR, accompanied by upregulation of regulatory proteins, plays an important role in receptor desensitization and may be important underlying mechanisms of RI in certain aging patients

RhoA/ROCK Pathway is the Major Molecular Determinant of Basal Tone in Intact Human Internal Anal Sphincter

Poster presented at: Digestive Disease Week (DDW) International meeting in San Diego, California. Background and Aims Knowledge of molecular control mechanisms underlying the basal tone in the intact human IAS is critical for the pathophysiology and rational therapy for debilitating rectoanal motility disorders

Basal internal anal sphincter tone, inhibitory neurotransmission, and other factors contributing to the maintenance of high pressures in the anal canal

Maintenance of the basal tone in the internal anal sphincter (IAS) is critical for rectoanal continence. Effective evacuation requires a fully functional rectoanal inhibitory reflex (RAIR)-mediated relaxation of the IAS via inhibitory neurotransmission (INT). Systematic studies examining the nature of the INT in different species have identified nitric oxide (NO) as the major inhibitory neurotransmitter. However, other mediators such as vasoactive intestinal polypeptide (VIP), ATP, and carbon monoxide (CO) may also play species-specific role under certain experimental conditions. Measurements of the intraluminal pressures in the IAS along with the force of the isolated IAS tissues are the mainstay in the basic studies for the molecular mechanisms underlying the basal tone and in the nature of the INT. The identification of NO as the inhibitory neurotransmitter has led to major advances in the diagnosis and treatment of a number of rectoanal motility disorders associated with the IAS dysfunction. Besides the IAS, the high pressures in the anal canal are affected by the external anal sphincter (EAS) function, and its malfunction may also lead to rectoanal incontinence. Different approaches including biofeedback have been attempted to improve the EAS function, with variable outcomes. There is a dire need for the innovative ways to improve the week high pressures zone in the anal canal. This viewpoint focuses on two studies that extend the above concept of multiplicity of inhibitory neurotransmitters (Neurogastroenterol Motil 2011 23 e11–25), and that high pressures in the anal canal can be improved by the EAS plication (Neurogastroenterol Motil 2011 23 70–5)

Urinary ascites in a preterm female neonate: a rare case report

Here we report a rare case of urinary ascites due to spontaneous bladder rupture in a preterm female neonate. The baby presented with respiratory distress, abdominal distension, anuria, and renal insufficiency. The diagnosis of bladder rupture was confirmed by peritoneal fluid aspiration with biochemical analysis and ultrasonography abdomen. The patient was managed successfully by establishing urinary outflow with indwelling Foley’s catheterization of the urinary bladder.Keywords: bladder rupture, neonate, urinary ascite

A Linear Antenna Array Failure Correction with Null Steering using Firefly Algorithm

The element failure of digital beam forming array antenna systems used in defence equipment increases the side lobe power level which distorts the beam pattern of the antenna array. The problem of array failure correction becomes more complex when null steering conditions are required to be added. In this paper, the problem of linear antenna array failure has been addressed with multiple wide band null steering using firefly algorithm (FA) by controlling the amplitude and phase excitation of array elements. A fitness function in the form of template has been formulated to obtain the error between original (pre-failed) side lobe pattern and measured side lobe pattern and this error function has been minimized using FA. Numerical example of element failure correction of element failure of array along with multiple nulls is presented to show the capability of this flexible approach.Defence Science Journal, 2014, 64(2), pp. 136-142. DOI: http://dx.doi.org/10.14429/dsj.64.425

Giant Vascular Malformation in an Infant’s Hand

Medical Imag

Aging-associated changes in microRNA expression profile of internal anal sphincter smooth muscle: Role of microRNA-133a.

A comprehensive genomic and proteomic, computational, and physiological approach was employed to examine the (previously unexplored) role of microRNAs (miRNAs) as regulators of internal anal sphincter (IAS) smooth muscle contractile phenotype and basal tone. miRNA profiling, genome-wide expression, validation, and network analyses were employed to assess changes in mRNA and miRNA expression in IAS smooth muscles from young vs. aging rats. Multiple miRNAs, including rno-miR-1, rno-miR-340-5p, rno-miR-185, rno-miR-199a-3p, rno-miR-200c, rno-miR-200b, rno-miR-31, rno-miR-133a, and rno-miR-206, were found to be upregulated in aging IAS. qPCR confirmed the upregulated expression of these miRNAs and downregulation of multiple, predicted targets (Eln, Col3a1, Col1a1, Zeb2, Myocd, Srf, Smad1, Smad2, Rhoa/Rock2, Fn1, Tagln v2, Klf4, and Acta2) involved in regulation of smooth muscle contractility. Subsequent studies demonstrated an aging-associated increase in the expression of miR-133a, corresponding decreases in RhoA, ROCK2, MYOCD, SRF, and SM22α protein expression, RhoA-signaling, and a decrease in basal and agonist [U-46619 (thromboxane A2 analog)]-induced increase in the IAS tone. Moreover, in vitro transfection of miR-133a caused a dose-dependent increase of IAS tone in strips, which was reversed by anti-miR-133a. Last, in vivo perianal injection of anti-miR-133a reversed the loss of IAS tone associated with age. This work establishes the important regulatory effect of miRNA-133a on basal and agonist-stimulated IAS tone. Moreover, reversal of age-associated loss of tone via anti-miR delivery strongly implicates miR dysregulation as a causal factor in the aging-associated decrease in IAS tone and suggests that miR-133a is a feasible therapeutic target in aging-associated rectoanal incontinence

Dicephalic parapagus twin - A rare case report

We are reporting a rare case of a dicephalic parapagus twin born to multigravida mother diagnosed antenatally few hours before birth by ultrasonography. The baby was born by emergency cesarean section. The baby was full-term live male baby; however, the baby expired few hours after birth. Due to the rarity of the case, we are prompted to report this case

Transient behaviour of induction motors in island conditions due to interruptions in the ship’s electrical power supply

The focus present dissertation was a problem that occurs in industrial installations and ships. The said installations experience overvoltage in case of power cut. This problem is a result of installing capacitive compensation parallel to motors. This dissertation studied this problem with two different electric motors widely used in big installations. The motors were tested in laboratory in different operational conditions; with different connections (D and WYE), with different loads and without load and with and without capacitive compensation. The capacitor bank, source of capacitive compensation, was also connected in D and WYE during the tests. The overvoltage was observed with capacitive compensation only when the capacitor bank was connected in D and the motors were connected in WYE. The mechanical load on the shaft has determined the peak value of the transient voltage and the duration of the waveform. The laboratory testing circuits, in which the overvoltage was observed, were recreated in Matlab to validate the results obtained in real-world. The simulation results were very similar to their real-world counterparts in 3 of the 4 cases. In conclusion, the overvoltage has manifested when the voltage received by the capacitor bank was superior than the motor’s. The load has also played an important role in determining the peak value of transient of waveform