Monday, 6 November 2023

4 Signs You Should See a Stomach Doctor


 

Our digestive system is responsible for breaking down the food we eat into nutrients the body can use for energy and growth. However, when our digestive system runs into problems, it can affect our overall health and well-being. Symptoms such as abdominal pain, diarrhea, and constipation can be frustrating and even debilitating. If you have been experiencing any of these symptoms or other abnormal signs, it may be time to see a stomach doctor.

 

By Hannah Whittenly

 

Gastrointestinal problems such as acid reflux, irritable bowel syndrome, inflammatory bowel disease, and peptic ulcers can all cause uncomfortable symptoms that require medical attention. If left untreated, they may escalate into more severe health issues. Here are four signs that indicate you should see a gastroenterologist.

 

Chronic Abdominal Pain

 

If you experience chronic abdominal pain, it could be a sign of an underlying issue like gastritis or an ulcer. Generally, stomach pains after meals that last over an hour should not be ignored. The pain intensity can range from mild to severe impacts on your work and activities. Consulting with a stomach doctor helps alleviate the underlying problem.

 

Consistent Bowel Irregularities

 

If you have irregular bowel movements, such as diarrhea, constipation, or alternating between the two, you might have an undiagnosed medical condition. Moreover, blood in the stool, persistent bloating, or weight loss are concerning signs that need medical attention. You might have diarrhea due to food poisoning, celiac disease, or inflammatory bowel disease. Therefore, a stomach doctor must examine you to identify the underlying cause.

 

Regular Heartburn

 

Heartburn causes a sharp, burning sensation in the chest and throat, which worsens after consuming fatty foods or lying down. Regular heartburn is a sign of acid reflux disease, a condition whereby the esophageal lining's acid damages over time. Long-term untreated heartburn can lead to a more severe health condition, like Barrett's esophagus or esophageal cancer. It is crucial to have an endoscopy to diagnose and treat any medical problem.

 

Unexplained Weight Loss

 

Sudden weight loss without excessive restrictions, dieting, or effort indicates an underlying gastrointestinal condition. Weight loss without an apparent cause may indicate an intestinal issue like Crohn's disease, gluten intolerance, or celiac disease. Therefore, it's advisable to see a gastrointestinal doctor to investigate the cause.

 

In conclusion, ignoring stomach issues can negatively impact your life. Therefore, if you notice any of the four symptoms, it's best to see a stomach doctor for diagnosis and treatment. The skill and experience of a stomach doctor can uncover the root of your stomach problems and recommend adequate treatment or medication. Consulting with a stomach doctor will enable you to address these issues, lead a pain-free life, and allow your body to absorb the necessary nutrients for optimal performance.

 

Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Saturday, 4 November 2023

Advances in Non-Viral Vector Delivery Systems for Nucleic Acid Drugs

                                                                                                    Image: by Roland1952, CC BY-SA 3.0

Nucleic acid drugs are mainly divided into two major categories: small nucleic acid drugs and mRNA. Small nucleic acid drugs, also known as oligonucleotide drugs, include antisense nucleotides (ASO)small interfering RNA (siRNA), microRNA, nucleic acid aptamers, and others. mRNA products can be further categorized into mRNA vaccines and mRNA drugs.

 

By Carrie Taylor, Director of Business Development of BOCSCI 

 

Characteristics of Nucleic Acid Drugs

 

Nucleic acid drugs offer distinct advantages. Traditional small molecule and antibody drugs primarily function by binding to target proteins, but their development is often constrained by the druggability of these target proteins. In contrast, nucleic acid drugs modulate genes associated with protein expression, enabling them to regulate both intracellular and extracellular proteins, as well as membrane-bound proteins. Moreover, most nucleic acid drugs operate on the principle of base-pairing complementarity, making sequence design relatively straightforward once the target gene’s base sequence is known.

 

However, limitations such as instability, immunogenicity, low cellular uptake efficiency, and difficulties in escaping endocytic pathways have restricted the development of nucleic acid drugs. To address the challenges associated with the molecules themselves, the development of delivery carrier systems that facilitate the uptake of nucleic acids into target cells has become crucial. These delivery carriers need to overcome barriers both extracellularly and intracellularly, withstand nucleases in the bloodstream, enhance and assist in cellular uptake of nucleic acid drugs, and promote intracellular escape of the nucleic acid drugs once inside the cell.

 

Nucleic Acid Drug Delivery System

 

In the early stages of research, viruses were commonly used as carriers for delivering nucleic acids. Virus carriers utilized in clinical trials included adenovirus (Ad), adeno-associated virus (AAV), lentivirus (LV), herpes simplex virus (HSV), and others. However, some virus carriers exhibited undesirable characteristics, such as potential carcinogenicity and high immunogenicity, which led to serious clinical adverse events and hindered the research on their clinical applications. With the development of materials and preparation techniques, non-viral carriers that are cost-effective, easily synthesized, purified, and possess high transfection efficiency with low immunogenicity have emerged as the “optimal candidates” for delivering nucleic acid drugs.

 

1. GalNac  Modification

 

GalNac (N-acetylgalactosamine) conjugate modification is the most commonly used nucleic acid drug delivery system today. GalNac is a lactose analog covalently attached to the 3′ end of nucleic acids in a trivalent form.

 

Following subcutaneous injection of GalNac-siRNA conjugates, they can rapidly enter the liver through the circulatory system. Subsequently, they are rapidly internalized by liver cells through ASPGR receptor-mediated uptake, accumulate in lysosomes, and are slowly released, continuously loading onto the RNA

 

Currently, drugs modified with GalNAc primarily include GalNAc-antisense oligonucleotides (ASO) and GalNAc-siRNA. Since effective ASOs for therapy have already undergone extensive modifications, a delivery carrier is not necessary. siRNAs, on the other hand, are prone to degradation on their own, so carrier delivery technologies are often employed.

 

2. Nanoparticles

 

(1) Lipid Nanoparticle

 

Lipid Nanoparticle (LNP), is one of the important technologies in lipid carrier drug delivery system. The main components are categorized into the following four types:

 

 

    1. Ionic lipids that can be ionized are the most crucial excipients and serve as determinants of delivery and transfection efficiency. Due to their relatively easy uptake by antigen-presenting cells, they are commonly used in vaccines.
    2. Neutral helper lipids, typically saturated lipids, can increase the phase transition temperature of cationic liposomes, support the formation of a lamellar lipid bilayer structure, and stabilize its structural arrangement.
    3. Cholesterol, possessing strong membrane fusion capabilities, facilitates intracellular uptake and cytoplasmic entry of mRNA.
    4. PEGylated lipids, located on the surface of lipid nanoparticles, enhance their hydrophilicity, prevent rapid clearance by the immune system, prevent particle aggregation, and increase stability.

     

    (2) Polymer Nanoparticles

     

    Cationic polymers have become another major type of non-viral gene delivery vector due to their ease of synthesis and flexibility. Polymers can bind with nucleic acids to form polycomplexes at physiological pH, facilitating gene delivery. Typically, polymer nanoparticles contain positively charged units that promote electrostatic binding with nucleic acids. Additionally, covalent linkage between nucleic acids and polymers can be achieved using degradable linkers. Common polymer materials include polyethylenimine (PEI) and chitosan (CS).

     

    Another class of polymers used for RNA delivery is dendrimers. These large molecules have a core molecule at their center and are synthesized through repeated growth reactions, resulting in highly branched polymers. Dendrimers carrying cationic groups can form complexes with RNA. Research has shown that they can deliver RNA to the central nervous system and siRNA to liver endothelial cells. Modifying the structure of dendrimers can protect nucleotides from enzymatic degradation.

     

    siG12D-LODER is a biodegradable polymer matrix containing siRNA targeting KRASG12D. Currently, Novartis is conducting Phase II clinical trials for siG12D-LODER to assess its effectiveness in combination with chemotherapy drugs like gemcitabine and paclitaxel in treating locally advanced pancreatic cancer patients.

     

    (3) Inorganic Nanoparticles

     

    Gold nanoparticles have unique optical properties, ease of synthesis and surface functionalization, and can be selectively and synergistically modified with nucleic acids through covalent or non-covalent affixation. Nucleic acid chains are covalently attached to the gold nanoparticle core (typically 13-15 nm) via thiol groups. This strategy can be used for DNA and siRNA, which can be directly attached to gold cores or polymer-modified gold cores.

     

    Spherical nucleic acids (SNA) are composed of nucleic acids arranged on the surface of small spherical gold nanoparticles. The platform drug, NU-0129, is currently being studied in a clinical phase 1 study in recurrent glioma. Once NU-0129 crosses the blood-brain barrier and enters the tumor, the nucleic acid component is able to target a gene called Bcl2L12. The researchers believe that targeting the Bcl2L12 gene with NU-0129 will help stop the growth of gliomas.

     

    Silica nanoparticles (100-250 nm in diameter), are used for nucleic acid delivery due to their good biocompatibility and tunability. Typically, nucleic acid molecules are loaded into silica nanoparticles through weak non-covalent interactions. Small pore (2.5-5 nm) silica nanoparticles are suitable for delivery of small siRNA.

     

    Iron oxide nanoparticles (consisting of Fe3O4 or Fe2O3) have superparamagnetic properties of a certain size and show success as delivery carriers and magnetothermal based therapies. Cationic iron oxide nanoparticles and anionic nucleic acid drugs, bind to each other by electrostatic forces. 50-100 nm lipid-coated iron oxide nanoparticles show optimal siRNA delivery activity.

     

    3. New Delivery Systems

    (1) Exosomes

     

    Extracellular vesicles, derived from endosomes and released into the extracellular space through multivesicular body fusion with the cell membrane, are membrane-bound vesicular structures with diameters ranging between 50 and 150 nm. These extracellular vesicles contain various biological macromolecules, including proteins, nucleic acids, and lipids. Extracellular vesicles can transfer a variety of biological macromolecules between cells, making them a drug delivery method with significant inherent advantages.

     

    1. Firstly, extracellular vesicles are “naturally tamed” nanocarriers that inherently contain multiple active components, allowing them to carry a wide range of drug types, including small molecules, nucleic acids, and recombinant proteins.
    2. Secondly, as endogenous nanoparticles, extracellular vesicles have low immunogenicity, resulting in high safety.
    3. Thirdly, extracellular vesicles can circulate through all the body’s cavities, exhibiting good tissue selectivity.
    4. Finally, complex engineering modifications can be applied to extracellular vesicles through genetic or chemical approaches, allowing precise control over their composition and biological functions, thus better serving our therapeutic purposes.
     

    (2) Peptides

    The current technologies used in nucleic acid drug delivery that are on the market today do not effectively address the issue of tissue-specific targeting. Peptides offer solutions to many problems that other delivery systems cannot resolve. Chemical modifications of non-natural amino acids have greatly improved the half-life of peptide drugs in the body. The development of cyclization techniques has increased the rigidity of peptide structures, significantly enhancing their affinity for target proteins. Peptide-drug conjugates (PDCs) exhibit strong tumor penetration, low immunogenicity, and renal metabolism, among other characteristics.

     

    Currently, companies like Ionis, Alnylam, Entrada Therapeutics, and others are actively establishing platforms for peptide-nucleic acid conjugate drugs. The future looks promising for peptide-nucleic acid conjugates.

     

    (3) Others

     

    Renowned scientist Zhang Feng’s company, Aera Therapeutics, has introduced a novel delivery platform called Protein Nanoparticles (PNP), which utilizes endogenous human proteins to address the limitations of current delivery technologies.

     

    Altamira Therapeutics, a biotechnology company focused on RNA therapy, has announced the development of an innovative peptide-based SemaPhoreTM nanoparticle technology platform. This delivery platform is designed for safe and effective systemic or local administration of oligonucleotides such as siRNA and mRNA to target cells. Currently, the company has established two preclinical siRNA projects on this platform for the treatment of KRAS-driven cancers and rheumatoid arthritis.

    Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

    Thursday, 2 November 2023

    5 Things You'll Need after Tearing Your ACL


    An anterior cruciate ligament (ACL) tear is a common injury among athletes, especially those involved in sports that require sudden, pivoting movements like basketball, soccer, and football. According to studies, about 250,000 people experience this injury in the U.S. each year. While it can be a devastating and painful experience, it is treatable with physical therapy, surgery, and the right tools. This blog post is going to explore the five things you'll need after tearing your ACL. These tools will help you heal faster and reduce the risk of re-injury.

     

    By Lizzie Weakley

     

    Knee Brace

    A knee brace is one of the most important tools you'll need to aid recovery after a torn ACL. It provides support to the knee and helps to stabilize it, reducing the risk of further injury. A knee brace also helps to reduce swelling, pain, and discomfort, making it easier for you to move around. There are many types of knee braces out there, from hinged and compression to ROM and post-op braces. Your doctor or physical therapist will recommend the orthopedic rehab equipment that suits your needs.

    Crutches

    After an ACL injury, your doctor will most likely advise you to stay off your feet and use crutches for a while. Crutches help to keep the weight off your injured knee, reducing pressure and preventing further damage. They also allow you to move around easily and perform daily activities like going to the bathroom or showering. If you're using crutches, make sure to practice proper technique and use them correctly to avoid further injury.

    Ice Pack

    An ice pack is another essential tool you'll need after tearing your ACL. It helps to reduce swelling, pain, and inflammation, promoting healing and reducing recovery time. Ice packs come in different forms and shapes, from gel packs and ice cubes to ice wraps and bags. Your doctor or physical therapist will recommend the best type for your needs.

    Physical Therapy

    Physical therapy is an integral part of ACL tear recovery. It helps to restore your knee's range of motion, strength, and flexibility, reducing the risk of re-injury. Physical therapy may include exercises, stretches, massages, and other therapies that target your injured knee. Your physical therapist will create a customized treatment plan based on your needs, goals, and level of fitness.

    Positive Attitude

    Finally, a positive attitude is crucial when recovering from an ACL tear. It's normal to feel frustrated, sad, and impatient after an injury, but a positive mindset can go a long way in speeding up recovery and

    reducing stress. Surround yourself with supportive friends and family, set achievable goals, and celebrate small victories. Remember to be kind to yourself and give yourself time to heal.

    Recovering from an ACL tear can be a long and challenging journey, but with the right tools, it's possible to heal faster and reduce the risk of re-injury. A knee brace, crutches, ice pack, physical therapy, and a positive attitude are five things you'll need after tearing your ACL. Remember to consult your doctor or physical therapist before using any of these tools and to follow their instructions to the letter. Keep a positive outlook, believe in yourself, and trust in the healing process. With patience, determination, and the right support, you'll be back on your feet in no time!

     

    Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

    Wednesday, 1 November 2023

    Risk of viral airborne transmission peaks within 5 seconds

     


    Scientists have successfully visualized and measured the flow field of aerosol particles derived from exhaled air and examined the risk of viral exposure during face-to-face encounters, such as while walking, jogging, running, or sprinting.

    The results, from the University of Tsukuba, showed that the number of aerosol particles during face-to-face encounters peaked within 5 seconds after the encounter and rapidly declined thereafter.

    The researchers identified the risk of virus exposure by visualizing and measuring the flow field of aerosol particles derived from exhaled air (jet stream) during face-to-face encounters using a mobile full-scale mannequin and a particle-tracking velocimetry system. Subsequently, the researchers compared the differences between aerodynamic characteristics with and without ventilation and their effects on the risk of virus exposure.

    The researchers found that, with or without ventilation, the number of aerosol particles peaked within 5 seconds after face-to-face encounters and then declined rapidly. The higher the transit velocity, the smaller this peak became, which may be due to the increase in the relative velocity between exhaled air and ambient air that facilitated particle diffusion. Furthermore, the number of aerosol particles in ventilated conditions was significantly lower than that in nonventilated conditions.

    The results indicate that, to reduce the risk of viral infection during face-to-face encounters, measures such as interrupting inhalation, maintaining a physical distance of at least 1 m, and positioning oneself upwind, are effective within 5 seconds of face-to-face encounters. These findings can help in the management of exposure risk to airborne viruses in general.

     

    See: Takeshi Asai, Erina Kurosaki, Kaoru Kimachi, Masao Nakayama, Masaaki Koido, Sungchan Hong. Peak risk of SARS-CoV-2 infection within 5 s of face-to-face encounters: an observational/retrospective study. Scientific Reports, 2023; 13 (1) DOI: 10.1038/s41598-023-44967-x

    Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

    Tuesday, 31 October 2023

    Wellness Strategies for Pharmacists: Nurturing Health and Resilience

     

    Pharmacists work very demanding jobs. Not only do they interact daily with patients, but they also spend long hours processing, handling, managing, and filing medications — work that requires a high level of attention to detail. 

     

    By Indiana Lee

     

    Studies show that since the pandemic, 51% of pharmacists have experienced burnout associated with long working hours, excessive workloads, and high prescription volumes. Those rates remain high among pharmacists in particular for a variety of reasons. Most notably, the pharmacy profession is not as extensively studied and thus doesn’t get the attention it needs for better-developed burnout solutions.

     

    For this reason, pharmacists must find ways to prioritize their health and stress to avoid negative outcomes. Not only can continued stress and burnout impact the well-being of pharmacists but it can also start to impact their ability to do their job, which can negatively affect patient care.

    How Stress Can Affect the Body

    Pharmacists, like many other healthcare professionals, tend to work long hours and are expected to meet high expectations. Unfortunately, if the stress that their job causes goes unmanaged, it can lead to several physical and even mental health issues.

     

    Both acute and chronic stressors can cause the “fight or flight” response in the body, according to the Harvard School of Public Health. This causes hormones to release that can cause several reactions including higher blood pressure, faster heart rate, and difficulty breathing. Stress hormones also deactivate certain functions to allow the body to focus on the stress response, such as reproduction, growth, and digestion.

     

    In fact, there is a strong connection between stress and issues with the gut. If the gut microbiome is impacted, it can negatively affect various other functions in the body, such as the immune system and neurological functions.

     

    Overall, some of the many health risks that can develop as a result of unmanaged stress in those who work demanding jobs, such as pharmacists, include:

     

         Weight gain

         Heart disease

         Skin conditions

         Muscular pain

         Insomnia

         Infertility

         Elevated blood pressure

         Digestive issues

     

    Constant stress can also lead to mental health problems, like anxiety and depression. Unfortunately, once mental health becomes affected, it can further impact physical health, creating a cycle of chronic problems that are difficult to manage.

    Health and Wellness Strategies to Help Pharmacists

    Healthcare jobs are inherently more demanding and stressful than those in other industries. However, this doesn’t mean that pharmacists should have to learn to live with the stress they experience daily. Managing stress in a high-pressure industry like the pharmaceutical field is necessary if workers want to be able to continue in that industry without suffering serious negative consequences, both for their own health and for the patients they interact with.

    Practice Better Time Management and Delegation

    In some cases, stress can arise from a lack of time management and taking on too many duties alone. There are a lot of different tasks pharmacists have to navigate throughout the day, so it can help to seek out a routine that could allow for more downtime during the day if possible.

     

    Understandably, part of the problem can be that pharmacies are simply understaffed,. If that is the case, pharmacists should not be afraid to stand up for their needs with their employer and ask for more help so tasks can be delegated more effectively. If staffing needs cannot be met, it may be necessary to close the pharmacy for temporary periods, such as in the middle of the day, so the pharmacists can take a break and attend to their needs.

    Eat Healthy, Regular Meals

    Those who work demanding jobs often find it hard to eat well throughout the workday. However, pharmacists need to eat healthy so they have the energy needed to stay on their feet and focused all day.

     

    Meal planning ahead of time can help. Instead of trying to think of something last minute, set some time aside to put together healthy meals that you can easily grab and eat on the go and take to work with you. Eating well when you are not working is also important to help you manage stress and keep your immune system strong.

     

    There are also certain foods that can specifically help fight stress. This includes foods high in antioxidants, such as kale, beans, tomatoes, blueberries, and beetroot. Omega-3 fatty acids are also great for fighting inflammation, which can occur as a stress response.

     

    You should also eat plenty of fruits and veggies as they are high in essential vitamins needed to help keep your body functioning properly. Some fruits and vegetables also have strong antibacterials and antimicrobial properties, like blueberries and ginger, which can help you have better oral health.

     

    Nutrition can also impact other facets of your health, such as your oral health. Foods that are good for oral health include whole grains and dairy products. Whole grains also have more dietary fiber, which can help with digestion.

    Practice Self-Care

    When working a high-stress job, it is necessary to practice self-care outside of work to help relax and find an outlet for the stress. This includes standard habits like getting a good night’s sleep and regular exercise, but it can also include things like talking to someone and finding support, taking up creative hobbies, journaling, or even meditating.

    Address Anxieties

    In some cases, stress for pharmacists can come from specific things that are triggering anxiety, such as a coworker who is difficult to work with or general social anxiety from interacting with people daily. To help reduce stress, it may be necessary to address the things that are causing your anxiety.

     

    If it’s someone you work with, try talking to them calmly and see if there is a way to resolve your issues in a healthy and constructive manner. If you have general social anxiety, make a list of things that trigger you and be proactive about planning out a way to deal with those situations ahead of time.

    Final Thoughts

    Working as a pharmacist is, by nature, a stressful job. However, that does not mean you should live with constant stress. Instead of pushing through the stress, it’s important to address it to ensure you and your customers are happier and healthier.

     

    Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

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