Ca2+ channel antagonist actions in bladder smooth muscle: comparative pharmacologic and [3H]nitrendipine binding studies

The actions of a series of 15 Ca2+ channel antagonists including D-600, nifedipine, and diltiazem were examined against K+ depolarization and muscarinic receptor induced responses in guinea pig bladder smooth muscle. Responses of bladder are very dependent upon extracellular Ca2+ and sensitive to the Ca2+ channel antagonists, the tonic component more than the phasic component of response. Regardless of stimulant, K+ or methylfurmethide (MF), or component of response, the same rank order of antagonist activities is expressed, suggestive of a single structure-activity relationship and the existence of a single category of binding site which may, however, exist in several affinity states. High affinity binding of [3H]nitrendipine (KD = 1.1 X 10(-10) M) occurs in bladder membranes, and similar high affinity binding was found in microsomal preparations from other smooth muscles including guinea pig and rat lung, rat vas deferens, uterus, and stomach. [3H]nitrendipine binding in the bladder was sensitive to displacement by other 1,4-dihydropyridines, paralleling their pharmacologic activities and showing excellent agreement with binding data previously obtained for guinea pig ileal smooth muscle. Comparison of pharmacologic data for inhibition of K+- and MF-induced responses by a common series of Ca2+ channel antagonists in bladder and ileum revealed excellent correlations. Neither pharmacologic nor binding studies suggest significant differences in Ca2+ channel antagonist properties in smooth muscle from bladder and intestine.     

Scalp reconstruction with a prefabricated abdominal flap carried by the radial artery.

Custom prefabrication of free flaps provides an unlimited variety of applications, since flaps can be created with expendable tissues and without restriction to naturally occurring vascular territories. These principles also can be used to customize flaps that could not be completed by conventional means. We report a case of scalp reconstruction using a random-pattern abdominal flap in which a radial artery fascial flap was induced to serve as the vascular carrier. In addition to providing durable scalp coverage, the prefabricated free flap enabled salvage of an abdominal flap that would otherwise have been aborted after intermediate transfer to the forearm.     

Inhibitory actions of a series of Ca2+ channel antagonists against agonist and K+ depolarization induced responses in smooth muscle: an assessment of selectivity of action

The inhibitory effects of the Ca2+ channel antagonists D-600, diltiazem, nifedipine and seven 1,4-dihydropyridine analogs of nifedipine against 80 mM K+ depolarization induced responses in guinea pig trachea, parenchyma, and pulmonary artery and rat renal and mesenteric artery preparations were determined. Together with similar data previously obtained for guinea pig ileum and bladder, these data permitted an assessment of tissue selectivity of action in smooth muscles of a series of Ca2+ channel antagonists under constant conditions (saline composition) and an identical challenge (K+ depolarization). Very similar rank orders of activity were expressed in all tissues suggesting that the same basic structure-activity relationship operates. However, the series of antagonists were significantly less active in respiratory smooth muscle than in other visceral or vascular smooth muscles. pA2 values for a series of 1,4-dihydropyridine antagonists measured in guinea pig taenia coli against Ca2+-induced responses in K+-depolarizing media correlated with mean inhibitory concentration values against K+-induced responses, suggesting that the latter were an appropriate measure of antagonist potency. pA2 values measured for nifedipine, D-600, and diltiazem against Ca2+-induced responses in taenia coli in the presence of a depolarizing K+ saline, or methylfurmethide, histamine, or 5-hydroxytryptamine did not differ, suggesting that the same channels were activated regardless of stimulant.     

Molecular phylogenetic study of flavonoids in medicinal plants: a case study family Apiaceae

Journal of Plant Research - The current study examined the phylogenetic pattern of medicinal species of the family Apiaceae based on flavonoid groups production, as well as the overall mechanism of...     

Embryonic development and organogenesis in the snail Marisa cornuarietis (Mesogastropoda: Ampullariidae). V. Development of the nervous system.

The nervous system is ectodermal in origin. All nerve ganglia arise separately by proliferation and later delamination from the ectoderm, not by invagination. They become secondarily connected to one another by commissures and connectives developing as extensions from the peripheral layer of ganglionic nerve cells. Rudiments of the cerebral, pedal, pleural and intestinal (parietal) ganglia arise almost simultaneously at a relatively early stage (Stage V). The cerebral ganglia develop from the ectoderm of the head plates. Rudiments of the pedal and pleural ganglia are separate at their inception. They later fuse (Stage VI) to form a pleuro-pedal ganglionic mass on each side. The 2 intestinal ganglia are symmetrical at the beginning, but they soon lose their symmetry as a result of torsion. The right ganglion crosses to the left over the gut and persists as the supraintestinal ganglion. The left or subintestinal ganglion shifts to the right and forward, and fuses with the right pleural ganglion (Stage VIII), thus obscuring the chiastoneury. The paired buccal and single visceral (abdominal) ganglia start differentiating in Stage VII. The former develop from the ectodermal wall of the stomodaeum, while the visceral ganglion delaminates from the right wall of the visceral sac, then shifts to the left during torsion. The statocysts develop early (Stage V) from 2 ectodermal invaginations on either side of the rudimentary foot. They later separate from the overlying ectoderm and statoconi appear in their lumina. Contrary to earlier reports on related ampullariids, the osphradium proved to be ontogenetically older than the mantle and mantle cavity. It starts differentiating as a thickened ectodermal plate in the right wall of the visceral sac (Stage V). During torsion, it becomes engulfed in the mantle cavity and shifts to the left side, then is carried forward as the mantlegrow. The eyes develop late (Stage IX) as ectodermal invaginations which rapidly separate from the ectoderm to form closed vesicles. Their cells start differentiating before hatching to form the retina, in which pigment is deposited, and the inner cornea. The lens is secreted in the lumen of the eye and grows by addition of concentric layers of secretion.     

Modeling of Fiber Optic Gold SPR Sensor Using Different Dielectric Function Models: A Comparative Study

The performance of surface plasmon resonance (SPR) sensors has great dependence on its plasmonic material’s frequency response, which is described by the complex dielectric function. Through history, researchers developed and enhanced mathematical models to accurately describe the material dielectric function. Although many papers compared the accuracy of different dielectric function models and stated its limitations, none of it addressed the effect of dielectric function model on the SPR sensor’s characteristics. In this paper, we investigated the performance of the three most used dielectric function models (Drude, Lorentz-Drude, and Brendel-Bormann) and their effect on the theoretically obtained sensor parameters when used in a gold SPR sensor’s model and validated it with the experimentally measured dielectric function. The result showed that using less accurate dielectric function’s model has a drastic effect on the theoretically obtained sensor’s parameters. Among the three models, the widely used Drude model was not the most accurate; alternatively, Brendel-Bormann model was the most accurate.

     

In vivo glucose-6-phosphatase inhibitory,toxicity and antidiabetic potentials of 2-picolylamine thioureas in Swiss albino mice

The 2-picolylamine is a simplest analogue of the alkaloid that has secondary and tertiary nitrogen function in its cyclic structure like that of alkaloids that can be derivatized to a number of biologically active compounds. In connection to our previous work, in the present work, three thiourea derivatives (I = 1,3-bis(2-benzyl-3-phenyl-1-(pyridine-2-yl) propyl) thiourea, II = 1,3-bis (pyridin-2-ylmethyl) thiourea, and III = 1-(2-benzyl-3-phenyl-1-(pyridine-2-yl) propyl)-3-phenylthiourea) were synthesized using 2-picolylamine template which is a readily available synthetic analogue of naturally occurring alkaloid. The biological effect of the synthesized derivatives were monitored on the activity of glucose-6-phosphatase in Swiss albino mice (21-days). The derivatives were also tested for their potential toxicity in a 28-days sub-chronic toxicity studies by assessing their effects on different parameters like hematological, serum biochemistry and liver histology. The therapeutic effect of the safe derivative (I) was examined in streptozotocin-induced diabetic mice as well. The derivatives showed inhibition of the enzyme activity from good to an excellent degree. Compound I had the highest inhibition with 21.42 ± 5.113 mg of the released phosphate as compared to that of the positive control group (84.55 ± 3.213 mg). Only I turned out to be safe for use in animals without exerting any toxic or lethal effects on any of the assessed parameters in the used animal model. Compound I efficiently reversed the effects like hyperglycemia, hyperlipidemia and weight loss in the test animals. Out of these three-tested compounds, I was found safe to be use as therapeutic agent in diabetes complications. However, further toxicological studies in other animal models are needed as well.     

Bioaccumulation of Key Metals and Other Contaminants by Seaweeds from the Egyptian Mediterranean Sea Coast in Relation to Human Health Risk

This study examined the bioaccumulation of key metals and other contaminants (SO₄, F, Na, K, Ca, Mg, P, Si, Fe, Mn, Zn, Ni, Co, Cu, and Cd) by seaweeds from the Egyptian Mediterranean Sea coast and their risk to human health. Bioaccumulation factor calculations indicated that S, F, Na, K, Zn, Cu, and Cd had high seaweed uptake and this referred to the potential pollution of the coastal area. Multivariate analysis of the studied contaminants confirmed the bioaccumulation factor results as well as the physiological processes in seaweeds. Human health risk assessment of F, Mn, Zn, Ni, Cu, and Cd was conducted using hazard quotient (HQ) and incremental lifetime cancer risk (ILCR) analyses. The carcinogenic assessment of sediments and ingestion of seaweeds using ILCR calculations revealed that Mn, Ni, and Cd in sediments and F and Zn in seaweeds require remedial action in order to reduce their human health risks. Additionally, HQ calculations for the contaminants in seaweeds and reference to toxicological references values from different agencies revealed that F and Co present high human health risk effects. Consequently, the potential public health risks from dietary exposure to hazardous contaminants in seaweeds must be continually subjected to research, regulation, and debate.     

CD154: the atherosclerotic risk factor in rheumatoid arthritis?

Atherosclerosis, now regarded as a chronic inflammatory disease of the arterial wall, and its clinical manifestations have increasingly been associated with rheumatoid arthritis (RA), supporting the notion that autoimmune diseases and vascular disorders share common etiological features. Indeed, evidence pertaining to this matter indicates that inflammation and its multiple components are the driving force behind the pathogenesis of these disorders. Interestingly, CD154 and its receptors have emerged as major players in the development of RA and atherosclerosis, which raises the possibility that this axis may represent an important biological link between both complications. Indeed, CD154 signaling elicits critical inflammatory responses that are common to the pathogenesis of both diseases. Here, we provide an overview of the traditional and disease-related interrelations between RA and vascular abnormalities, while focusing on CD154 as a potential mediator in the development of atherosclerotic events in RA patients.