The Caco-2 permeability assay has become the gold standard in vitro method to assess a test compound’s readiness for oral dosing.Why to Choose The Caco-2 Permeability Assay?Solubility and intestinal permeability are the important factors in determining the oral absorption of drugs. By evaluating compound permeability in early drug discovery, organizations can distinguish test compounds which are more likely to cause drug failure in the later stages of drug development due to poor intestinal permeability. Compounds with poor permeability and solubility are not likely to possess the favorable absorption, distribution, metabolism, and excretion parameters (ADME Parameters) for an investigational new drug and may cause drug failure in the clinic. The Caco-2 permeability assay is a United States FDA recommended in vitro method for the prediction of drug permeability.One of the key reasons the Caco-2 permeability assay is widely accepted by regulatory bodies is the Caco-2 cell line. The Caco-2 human colon carcinoma cell line has characteristics that mimic human epithelial cells found in the intestine such as the formation of a well-differentiated monolayer of cells containing a defined brush border on the apical surface. This monolayer of cells also contains many of the brush border enzymes that mediate the active uptake or efux of drugs in the human intestine.Because of the Caco-2 cell line’s ability to mimic human intestinal epithelial cells, the in vivo absorption of a compound in the intestine can be predicted by assessing the transport rate of a compound across a Caco-2 cell monolayer membrane. Additional assessments can be made, including whether a test compound is actively transported by P-glycoprotein (P-gp).Key Points About The Caco-2 Permeability AssayÏ The Caco-2 permeability assay is an FDA recommended assay for companies applying for an Investigational New Drug (IND).Ï The Caco-2 assay is utilized as an in vitro study for the human intestinal absorption of drugs. Ï When run with a reliable CRO, the Caco-2 permeability assay can predict the suitability of your test compound for oral dosing.Ï Additional assessments that can be made when running the Caco-2 permeability assay including an analysis on whether a test compound is actively transported by P-glycoprotein (P-gp). Selecting a Contract Research Organization (CRO) to Run a Caco-2 Study When looking to run a Caco-2 permeability study, check whether the company follows GCCP and GIVIMP guidelines. This is a good indicator of a company’s experience with in vitro techniques and what the quality of the data will be. Choose a professional CRO, which offers quality drug discovery services and provides guidance and support to clients for the discovery and development of novel drugs. IONTOX, L.L.C. is a contract research organization specializing in vitro methods. IONTOX ‘s Caco-2 permeability assay is overseen by a Diplomat of the American Board of Toxicology and all cell cultures follows the internationally recognized guidance documents on Good In Vitro Method Practices (GIVMP) and Good Cell Culture Practices (GCCP).To learn more about the Caco-2 permeability assay, visit https://www.iontox.com/caco-2-permeability-assay/ today.

Although MII strikingly reduces operational trauma and, accordingly, the length of hospitalization, it has significant technical disadvantages. The surgeon operates using a standard two-dimensional video monitor, instead of looking at his own hands. Video flattenes the natural depth of the surgical field, and fixed wrists and instruments limit motor capabilities. The lack of three-dimensional visualization of the surgical field, poor ergonomics and controllability are the main constraints on further progress. As a result, endoscopic surgery, as a form of IIR, limits its use to only a narrow circle of surgical interventions.

The revolutionary frontier in the development of surgical technology was achieved with the advent of the Da Vinci system. It is equipped with manipulators with artificial wrists having seven degrees of freedom (similar to a human hand) and three-dimensional intuitive visualization (3D monitor). These innovations created the prerequisites for minimally invasive complex operations in various fields of surgery.

The Da Vinci system improves surgical outcomes by fundamentally changing surgery in three ways:

Simplifying many of the operations already developed:
Many of the surgical procedures performed today using standard equipment can be performed faster and easier with the system, because Da Vinci creates “visibility and sensation” similar to open surgery.

By making complex minimally invasive operations routine.
By making possible new minimally invasive procedures:
A number of operations that could not be performed using traditional minimally invasive technologies can now be done using a surgical complex. The large EndoWrist toolkit allows surgeons to do more operations through small accesses.

The surgical system consists of an ergonomic surgeon console, a stand with four interactive robotic arms at the operating table, a high-performance InSite viewing system and patented EndoWrist tools. Armed with state-of-the-art robotic technology, the surgeon’s hand movements are scaled, filtered and evenly converted to the exact movements of EndoWrist instruments. The result is an intuitive interface with superior surgical capabilities.

Surgical System Components

The surgeon’s console
Using Da Vinci, the surgeon operates by sitting comfortably at the console and seeing a three-dimensional image of the surgical field.

The surgeon’s fingers grab the handles under the display, and his hands and wrists are naturally positioned in relation to his eyes. The system evenly translates the movements of the fingers, brushes and wrists of the surgeon into the exact movements of surgical instruments inside the patient in real time.

Stand at the operating table
The system rack holds up to four electromechanical hands manipulating tools. Tools and the camera are easily attached to the hands and easily moved from the console or assistant.

The first two hands of the robot, corresponding to the surgeon’s right and left hands, hold EndoWrist tools. The third hand holds the endoscope, allowing the surgeon to easily change, move, zoom in and turn the field of view from the console. This mobility eliminates the need for an assistant.

The fourth hand allows you to add a third EndoWrist tool and perform additional tasks, such as supporting continuous seam. This eliminates the need for another assistant.

The surgeon can simultaneously control any two hands using the pedals under the console.

EndoWrist Tools
Patterned after the human wrist, EndoWrist instruments have even greater range of motion than the human hand. They truly allow the system to advance surgical accuracy and technique beyond the capabilities of the human hand. Similar to human tendons, the EndoWrist internal tool cables provide maximum response, enabling fast and accurate suturing, dissection and tissue manipulation. A manipulator with a tool at its end has 7 degrees of mobility, like a human hand.

InSite review system
The InSite viewing system with a high-resolution 3D endoscope and image processing system provides a natural image of the surgical field. An endoscope controlled by a robotic arm, coupled with two 3-chip cameras, transfers the surgeon “inside” the patient.

The Intuitive Surgical video system is equipped with two independent image transmission channels paired with two high-resolution color monitors. The system also has image processing equipment consisting of two video cameras, edge enhancement algorithms and noise reduction.

The resulting high-resolution three-dimensional image is bright, clear and sharp, without tiring flickering and attenuation. Camera control through handles and pedals ensures smooth movement in the operating space. Moving the surgeon’s head on the console does not affect image quality.

Kitchen, the kingdom of the Queen of the house deserves to be equally ravishing as the rest of the house. And this is one area of the home where almost everything has to be useful and not only decorative. Today with the availability of numerous products available, who says an aesthetically appealing kitchen cannot be a practical one. And with professional kitchen cleaning services available it becomes an easy task to maintain the nook and cranny of your home.

We will tell you ways to get a fancy kitchen on a thrifty budget.

Fancy tiles:-
The market is full of tiles with designs to suit every taste and budget. The kitchen tiles no longer have to be the ones with photos of fruits and vegetables. Maybe a bright colored tile on one of the walls combined with a subtle colored tile on the rest of the walls will make the kitchen look brighter.

Colorful kitchen utensils:-
Supermarkets today are full of options in good rates for various kitchen utilities. Buy bright colored pots and pans to bring some oomph to the kitchen.

Back to school:-
We rely on post-its to remember tiny important things. Or in the worse case, we forget about it completely. And in such cases if you have painted a tiny section of your wall with black chalkboard paint, and use it as a blackboard to write down important things, or messages for your loved ones or even the menu for the day will be definitely a great idea to make your kitchen stand apart than that of your neighbours.

Add a brick wall:-
One way to make your kitchen look absolutely different from others, keep a brick wall or keep the entire kitchen that ways to give it a rustic look. Not only the maintenance will be easy, it will add a Mediterranean touch to your kitchen.

Accessorize:-
The online shopping websites have made us accessory junkies. The kind of items available on the internet that are unconventional but at the same time very handy. Like the batter dispenser, butter cutter, spiral slicer, a very useful self-draining sink caddy, colorful aprons, coasters with messages, coffee mugs in endless shape, the list is endless.

These were five ideas to spruce up your kitchen. And always remember that to maintain the wonderful home that you created with so much love will be better maintained with the help of Best Home Cleaning Services.

Something we generally tend to ignore but these services are a boon and help us keep our surroundings clean and healthy from deep within.

An ongoing outbreak of a novel coronavirus (SARS-CoV-2) has raised global concerns. It is identified as the cause of pneumonia with unknown etiology. Since the early outbreak in Wuhan, China, it has subsequently spread to all provinces of China and many other countries. In fact, coronavirus is a relatively common human virus, which causes 10% of the common colds. However, some coronaviruses are more harmful, such as SARS-CoV and MERS- CoV and the novel coronavirus, named SARS-CoV-2.

How does SARS-CoV-2 infect patients?

Spike protein (including S1 and S2 subunits) is the most important pathogenic protein of coronavirus, which helps the virus to bind to the transmembrane receptor protein on the human cell membrane, thereby helping itself to enter the cell.

The latest research shows that the Spike proteins of SARS-CoV-2 and SARS-CoV are more conserved, and in vitro experiments have proved that as long as the cell expresses ACE2, SARS-CoV-2 can infect cells; on the contrary, if there is no ACE2 on the cell protein, it will not be infected. Therefore, it is believed that SARS-CoV-2 is mediated into the interior of cells through the binding of Spike proteins to ACE2 proteins, which may become a breakthrough in the study of SARS-CoV-2.

What is ACE2 protein?

The ACE2 gene is located on the X chromosome, which encodes a type I transmembrane glycoprotein with a single extracellular catalytic domain. ACE2 has a well-known homologous gene, ACE, which is also an angiotensin-converting enzyme. ACE and ACE2 both have two domains: the amino-terminal catalytic domain and the carboxy-terminal domain).

Despite similarities, ACE2 and ACE function differently. ACE’s role is to convert angiotensin I (AngI) to active angiotensin II (AngII), thereby increasing hypertension. The role of ACE2 is to convert AngII to heptapeptide angiotensin 1-7 (Ang1-7), and then antagonize the blood pressure-increasing effect of AngII, which has a negative regulatory effect on the RAS system. Therefore, ACE2 functions completely differently from ACE and the two work together to balance blood pressure.

Lessons from SARS

Due to the function of ACE2, previous basic clinical studies have linked it with hypertension and cardiovascular disease, but in 2003, after ACE2 was identified as an essential receptor for SARS coronavirus infection, its research in this area has been carried out. And because the pathogenic mechanism of SARS-CoV-2 is highly similar to SARS of 2003, the current research of SARS is extremely informative.

In 2003, researchers identified ACE2 as a functional SARS-CoV receptor by co-immunoprecipitation technology. Subsequently, ACE2 was identified as an essential receptor for SARS infection in vivo in the ACE2-knockout mouse model. However, previous studies have found that ACE2-knockout mice with lung injury have a more severe acute injury and higher mortality than the wild-type mice, suggesting that ACE2 deficiency may worsen the symptoms of acute lung injury. Therefore, ACE2-mediated degradation of AngII is important for lung protection against the pathogenesis of pneumonia causing by SARS-CoV infection.

To unveil the secret of SARS-CoV-2, more research is needed, and at the same time, scientists worldwide are dedicated to finding methods of more accurate diagnosis and more efficient treatment.