Category Archives: Drug

NEW APPROACHES FOR TREATING ADDICTION

naltrexone-and-alcoholAddicts are often lumped into a single category, represented in the media as morally bankrupt and lacking in willpower. All the Addictive drugs affect the brain’s reward circuitry in similar ways. These drugs will trigger the Mesolimbic Dopamine System and the nucleus accumbens. When these drugs are taken for prolonged period, it can cause four roots of addiction states, by causing a long term impact to neurons.  They are Tolerance, Dependence, Dysphoria and Sensitization. If all drug substances work in a similar way, it can make an impact in one user to have greater or lesser willpower than other.

Prescription Opioid drugs are linked to the increase in heroin abuse. Prescription Opioids bind to the same receptor in brain as heroin. Therefore, the patients who are prescribed with heroin are also addicted to PO’s. And people who are addicted to Prescription Opioids are more likely to become addicted to heroin.naltrexone-implant

Stress hormones can reduce the drug desire. In the case of heroin, Cortisol can reduce its desire. Since cortisol inhibits the brain’s ability to retrieve memories, it is suggested that it can also reduce the heroin cravings.

Naltrexone, an alcohol antagonist is the most operative drug to reduce the alcohol dependence. In this case, a person has to take both the alcohol and naltrexone at a time. So that the naltrexone can bind to the opioids which is released from the alcohol and it can block the opioids to bind it to the brain’s receptor. Therefore, the person has to drink continuously by taking naltrexone to stop craving the alcohol.

DNA Drug Design for Cancer Therapy

6A direct genetic approach for cancer treatment is represented through DNA (antisense and other oligonucleotides (ODN’s)) drug design. This approach follows the mechanisms that activate genes known to confer a growth advantage to neoplastic cells. They have the ability to block the expression of these genes which allows exploration of normal growth regulation. As the Progress in DNA drug technology has been rapid, the traditional antisense inhibition of gene expression is now viewed on a genomic scale. Several antisense oligonucleotides are in clinical trials. These antisense oligonucleotides are well tolerated, and are potentially, therapeutically active. These drugs are promising molecular medicines for the treatment of human cancer in the near future.

Antisense or decoy DNA drugs can specifically inhibit gene expression and, as indicated in this review, can ultimately affect abnormal cell proliferation. Downregulation of genes that contribute to cancer progression has been the goal of antisense research, with the expectation that such an approach may lead to a selective or preferential inhibition of tumor growth without harming normal cell growth. Such targets include oncogenes, growth factors, cytokines, protein kinases, phosphoprotein phosphatases, and other positive intracellular regulators of cell growth and cell survival. Although a number of studies have demonstrated in vitro the efficacy of these ODNs against tumor growth, an examination of their long-term effects and pharmacological properties is warranted.

Recent advances in high-throughput screening of gene expression by microarray analysis would permit these studies. Results from these studies will not only provide critical information on ODN pharmacokinetics and toxicity, they will also provide insight into the mechanism of action of these molecules on their own targets and on total cellular gene expression. Such studies will thus narrow the number of selected target genes and the discovery of new target genes for antisense therapeutics.

Revisiting antisense-targeted gene expression on a genome-wide scale will facilitate the discovery of clinically appropriate antisense drugs and provide a unique perspective on the development of new chemotherapeutic combinations based on the molecular actions of these drugs.

Unlike conventional chemotherapy regimens, which depend on the maximum tolerated dose of a given drug to achieve optimal tumor-cell kill, treatment regimens involving antisense ODNs may rely more on the concept of an optimal biological dose. The ultimate goal of therapeutic ODNs is their use as long-term biological gene modulators with minimal or no toxicity. In that case, antisense ODNs represent cytostatic rather than cytotoxic drugs. As such, ODNs can induce tumor cells to differentiate or revert, eventually leading to apoptosis, and reduce or eliminate the chance of relapse in cancer patients following initial treatment. For utmost therapeutic effect, these biological target based antisense DNA drugs can be used at nontoxic minimum doses in combination with low doses of conventional cytotoxic drugs or radiation therapy for cancer.

Forceful prostate and lung cancers are driven by regular instruments

Specialists have found a typical procedure in the improvement recently arrange, little cell malignancies of the prostate and lung. These common atomic systems could prompt the improvement of drug and drug discovery to treat not simply prostate and lung growths, but rather little cell diseases of any organ. Prostate and lung cells have altogether different examples of quality articulation when they’re solid, however relatively indistinguishable examples when they change into little cell malignancies. The exploration proposes that diverse kinds of little cell tumors advance likewise, notwithstanding when they originate from various organs.1

Cancers that end up impervious to treatment frequently form into little cell growths, otherwise called little cell neuroendocrine carcinomas or SCNCs which for the most part have to a great degree poor forecast. Certain diseases can avoid treatment to some extent by changing cell composes from forceful adenocarcinoma to little cell carcinoma, for instance. Past clinical research implied that little cell growths from various organs might be driven by basic instruments, however, the study is the first to so obviously depict the means in their development.

Little cell malignancies of the lung, prostate, bladder, and different tissues were for some time thought to be comparable in name alone and they were dealt with by oncologists as various elements. In the course of recent years, however, specialists have progressively started to understand that there are similitudes in the diseases, and that is the thing that our work affirms. partners investigated the potential parallels between the malignancy composes by transplanting human prostate cells with five qualities, referred to all things considered as PARCB, into mice. At the point when those cells developed in the mice, they showed one of a kind highlights of human little cell neuroendocrine carcinomas.

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The group likewise distinguished that for little cell neuroendocrine carcinomas to create in the prostate, two tumor silencer qualities, TP53 and RB1, which are known for shielding typical cells from changing into disease cells, must be at the same time inactivated when PARCB was presented. Extra tests affirmed striking similitudes between the PARCB-SCNC cells and little cell prostate tumor cells from people. Specifically, RNA articulation and the turning on and off of specific qualities were about indistinguishable.

The group additionally took a gander everywhere databases of quality articulation, to think about the examples of quality articulation in their PARCB-SCNC cells to malignancies of different organs. They found that the example of quality articulation in PARCB-SCNC cells was to a great degree like those of both prostate and lung little cell malignancies. Next, they tried whether PARCB qualities could modify solid cells from human lungs into little cell lung growths, and the researchers found that they could. The group presently is taking a shot at mapping which qualities control the whole course of occasions that underlies the progress to little cell growth.

New Antibody Conjugates in Cancer Therapy

drug_conjugateTargeting of drugs, radiation and protein toxins to cancer selectively with monoclonal antibodies (MAbs) has been considerable as a topic of interest and an area of continued development. Radioimmunotherapy of lymphoma using directly labeled MAbs is of current interest after approval of two radiolabeled anti-CD20 MAbs, as illustrated with the near 100% overall response rate obtained in a recent clinical trial using an investigational radiolabeled 90Y-epratuzumab ,anti-CD22 MAb. The advantage of pre targeted RAIT over directly labeled MAbs is continuing to be validated in preclinical models of solid tumors and lymphoma. Importantly, the advantages of combining RAIT with radiation sensitizers, with immunotherapy, or a drug conjugate targeting a different antigen are being studied clinically and pre clinically. The area of drug-conjugated antibodies is progressing with encouraging data for the trastuzumab-DM1 conjugate in a phase I clinical trial in HER2-positive breast cancer. The technology of Dock-and-Lock platform has contributed to the design and the evaluation of antibody-toxin conjugates and complex antibody-cytokine.

RADIOIMMUNOCONJUGATES

Radioimmunotherapy (RAIT) involves in the application of radiolabeled MAbs for targeted radiotherapy (RT). Both directly radiolabeled MAbs and in vivo radiolabelings of tumor-targeted MAbs by complexation with radiolabeled haptens have been developed.

Radionuclides Used for RAIT

Tumoricidal effects produced by continuous low-dose irradiation from a tumor-targeted radiolabeled MAb. For therapy, α- and β-particle emitters are of practical relevance. There have been numerous investigations with a number of these radionuclides, but for use with whole antibodies, the most promising radionuclides are the β-emitters 131I, 90Y, and 177Lu. 90Y is a max-energy β-emitter (Emax: 2,280 keV; max range: 12 mm) with a 64-h half-life, while 131I has a higher half-life of 8.1 days with low-intermediate energy (610 keV, range: 2.0 mm). 131I is quickly removed from tumor cells after intracellular antibody catabolism so it is not suitable for use with internalizing MAbs. The forms of intracellularly trapped 131I have been designed by us and others for use with internalizing MAbs. A recent study of IMP-R4 template utilized for incorporating residualizing radioiodine for immuno-PET quantitation of de2-7 EGFR expression in glioma in a xenograft model using 124I-IMP-R4–labeled anti-EGFR antibody, ch806. Residualizing use of radioiodine method for clinical RAIT may be supplanted by the availability of the metallic radionuclide 177Lu, which has radiophysical properties similar to those of 131I and radiolabeling chemistry similar to that of 90Y.

New Drug Discovery for Pancreatic Cancer

A recent drug discovery can keep the most widely recognized sort of pancreatic cancer from developing and spreading in research facility mice, as indicated by another examination. The investigation likewise exhibited in mice that the medication, Metavert, may keep patients from building up a protection from as of now utilized pancreatic disease chemotherapies. As per the clinical research, it is an energizing advance toward enhancing survival rates in pancreatic cancer patients, If the outcomes are affirmed in people, the researchers could have a medication with the possibility to essentially expand the lives of patients with pancreatic ductal adenocarcinoma (PDAC), which is extremely hard to treat.

Ninety-five percent of pancreatic cancer patients are determined to have PDAC, which creates from cells lining little tubes in the pancreas. PDAC can be hard to treat on the grounds that the cancer cells incite typical cells that live in the pancreas, called stellate cells, to create pancreatic scar tissue. Scar tissue makes it troublesome for chemotherapy operators and blood to enter the pancreas. Cancer and stellate cell cooperation likewise make a domain that animates nearby tumor development and growth spread to inaccessible locales in the body. Also, the movement levels of specific catalysts rev up, filling protection from tumor medications.@1

Over a four-year time frame, the agents composed and integrated new chemicals that hinder disease cell movement. They found that Metavert blocked medication opposition and furthermore fundamentally helped the constructive outcomes of radiation and two chemotherapy specialists regularly utilized in people. In one of the mice considers, Metavert expanded the survival rate by around 50 percent. The examiners at present are building up a rendition of the medication to test in people.

Drugs Adverse effect & its classification

Adverse effect is ‘any undesirable or unintended consequence of drug administration’. it’s a broad term, includes all types of noxious effect—trivial, serious or maybe fatal. For the needs of detection and quantifying solely those adverse effects of a drug that square measure of some import and occur in normal therapeutic setting, the term adverse drug reaction (ADR) has been outlined as ‘any pestilent modification that is suspected to ensue to a drug, happens at doses usually utilized in man, needs treatment or decrease in dose or indicates caution within the future use of an equivalent drug’. This definition excludes trivial or expected side effects and poisonings or dose.

Another term ‘adverse drug event’ (ADE) has been wont to mean ‘any untoward medical occurrence that will gift throughout treatment with a drugs, however that doesn’t essentially have a causative relationship with the treatment’. the thought is to record all adverse events 1st, and appearance for
causality solely whereas analyzing pooled knowledge.
All medicine will turn out adverse effects, and whenever a drug is given a risk is taken. The magnitude of risk should be thought of beside the magnitude of expected therapeutic profit to decide whether or not to use or to not use a specific drug during a given patient, e.g. even risk of bone marrow depression could also be even in treating cancer, whereas delicate temporary state caused by associate degree antihistaminic in treating respiratory disease could also be unacceptable.1g

Fig; Adverse effects- nausea or vomiting, Headache, skin rash, chest pain

Adverse effects could develop promptly or solely when prolonged medication or maybe when stoppage of the drug. Adverse effects aren’t rare; associate degree incidence of 10–25% has been documented in several clinical settings. they’re a lot of common with multiple drug medical aid and within the older. Adverse effects are classified in some ways. They are-
Predictable (Type A or Augmented) reactions (mechanism based mostly adverse reactions) These square measure supported the medical specialty properties of the drug, which implies that they’re increased, however qualitatively traditional response to the drug; embody aspect effects, harmful effects and consequences of withdrawal. they’re a lot of common, dose connected and largely preventable and reversible.

Unpredictable (Type B or Bizarre) reactions These are based on peculiarities of the patient and not on drug’s known actions; include hypersensitivity reaction and specialness. they’re less common, usually non-dose connected, typically a lot of serious and need withdrawal of the drug. a number of these reactions is foretold and prevented if their genetic basis is thought and appropriate take a look at to characterize the individual’s composition is performed.

Severity of adverse drug reactions has been ranked as:
Minor: No medical aid, remedy or prolongation of hospitalization is needed.
Moderate: needs modification in drug medical aid, specific treatment or prolongs hospital keep by atleast someday.
Severe: doubtless grievous, causes permanent injury or needs intensive medical treatment.
Lethal: Directly or indirectly contributes to death of the patient.

New vaccine target for Malaria to control the birth of parasites

Malaria is an illness caused by the transfer of the Plasmodium parasite from bound mosquitos to humans, which is responsible for 429,000 deaths per annum in step with the World Health Organization. The life cycle of this parasite occurs within humans and mosquitos, permitting it to unfold spread at a great rate between the two species. Scientists have noticed that a protein concerned within the life cycle of the protozoal or malarial infection causing parasite is paving the way for a brand-new immunizing agent to scale back illness unfold. Most of the scientific community believe that the key to eliminating the illness is to prevent humans infected with the parasite from passing it on to doubtless dozens of mosquitos, every of which might then continue to infect more people.

On the surface of the reproductive cells of male protozoal infection, parasites may be a small molecule which is a protein referred to as HAP2 and it have discovered that by block it, simply targetable a part of the HAP2 molecule, fertilization between the male and feminine parasites is discontinuous. This ends up in protozoal infection parasites being unable to breed with efficiency, acting as a variety of parasitic birth control. In fertilization process, the male and feminine reproductive cells of the parasites would combine within the abdomen of their mosquito host, grow, then trip the secretion glands of the mosquito able to transmit the protozoal infection inflicting parasite once mosquito next bites an individual’s. Disturbing the method of fertilization prevents that can parasites from travel to the secretion glands of the mosquito, thereby reducing the transmission of the infecting parasite to humans.

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In initial in vitro studies, the team created an antibody that can blocks HAP2 and else it to blood infected with protozoal infection. They then ascertained the amount of winning fertilization events among the parasites that disclosed a big 85.88 percent reduction in comparison with an effect experiment wherever no protein was administered. Finally, the study examined by the scientists however the blocking approach of protein HAP2- affected the transmission of parasites between human blood and mosquitos, victimization blood samples of patient with protozoal infection. The patient blood was combined with antibodies that block HAP2 that resulted in 77 percent reduction in transmission of the parasite from human blood to infected mosquitoes.

It is an inexpensive and straightforward target within the seek for vaccines that may lower the transmission rates of protozoal infection.

Food Toxicology

The Toxicology is the branch of science that deals with the adverse effects of chemicals on living organisms and leads to fatal condition in living organism.

Toxicology is interface of chemistry and biology.
Pharmacology: therapeutic effect
Toxicology: toxicosis or disease effect
Food toxicology deals with physical, chemical and biological properties of food particles and detection of toxic substances in food, and their diseases and infections.

Some food items are poisonous and some are medicinal, stimulatory, hallucinatory, or narcotic effects.

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Toxicology in two categories: basic and Fundamental. Fundamental work on the molecular and biological processes of toxic substances is called Basic toxicology. Applying scientific knowledge to practical problems is called Applied Toxicology.

Toxicology vs. Risk analysis: In majority of Risk analysis only the applied toxicology is used to examine whether there is the presence of chemical, natural and anthropogenic is used. Risk analysis is broadly classified to include Risk assessment, Risk characterization, Risk communication, Risk management.2

Human health risk assessment: Predictive modelling of the toxicology to human health posed by the exposure to toxicants. • For constituents that are systemic toxicants, the threat can be expressed in terms of a hazard quotient. • Hazard Quotient = Dose ÷ Toxicity Factor. Systemic toxicity is a threshold phenomenon. – Increasing exposure (dose) of a chemical will cross a threshold when biological effects will start to occur. – The dose is the total dose attributable all routes of exposure. Dose is modeled with the following general equation (unit conversion factors are used as needed): Dose = CC × CR × EF ÷ (BW × UCF) • CC — constituent • CR — contact rate • EF — exposure frequency. • BW — body weight . • UCF — unit conversion factor.

Test drug trains in on malignancies related with Epstein-Barr infection

Epstein-Barr Virus (EBV) doesn’t straightforwardly cause malignancy, yet disease with this normal herpes infection brings an expanded danger of a few cancers, including quickly developing lymphomas. This week in mSphere, analysts write about another medication that works by focusing on EBV-positive tumors. In investigates mice, the medication restrained tumor advancement and metastases for EBV-related lymphomas. The discoveries propose the medication might be helpful in treating malignancies in EBV-positive patients and have prompted a stage I trial in that patient populace.1

The Epstein-Barr infection is common to the point that nearly everybody has been contaminated when they achieve their twenties. A contamination can cause mononucleosis (the “kissing sickness”), however numerous individuals stay asymptomatic their whole lives. An expanded danger of different sorts of tumor, including nasopharyngeal and stomach malignancies, has been related with EBV diseases.

Diseases by EBV are thought to advance the development of B lymphocytes, bringing about lymphomas. Significantly, EBV encodes a protein called LMP2A (Latent Membrane Protein 2A) that can seize the phone flagging component of the B cells it taints. Researcher has discovered that LMP2A can both anticipate apoptosis, or cell passing, and drive the cell-division cycle, advancing disease in murine models. For the new investigation, researchers considered mice that had been hereditary changed to express LMP2A protein in B cells that advanced lymphoma improvement. In treated mice, the medication, a tyrosine kinase inhibitor called TAK-659, neutralized the malignancy advancing systems of the LMP2A protein. The medication slaughtered tumor cells however left host cells unaffected. It likewise advanced apoptosis in tumor cells and halted the spread of tumor cells into close-by bone marrow. 2

In view of past clinical research, the organization propelled three stage I clinical preliminaries to test the wellbeing of the medication in patients with a few lymphomas, intense myelogenous leukemia, and some strong tumors. Those investigations are enrolling. In light of the discoveries distributed for the current week in mSphere, which approved the medication’s viability in EBV-positive lymphomas, the organization included a partner of EBV-positive patients to one of those preliminaries.

The medication has guarantee both as a solitary operator and in mix with other disease treatments, including immunotherapies, it consolidates extremely well with checkpoint inhibitors, researchers said that the new discoveries exhibit the medication’s adequacy can be tried among various sorts of growth, as well as more by and large among those related with EBV.

New Discovery for Chronic Kidney Disease

Specialists have built peptide nanoparticles to defeat the organic framework and focus on the kidney cells. The development may demonstrate basic to tending to unending kidney ailment. Since kidneys are the sifting specialists in our body, they are quick to dispose of little particles that they sense don’t have a place. Furthermore, if the kidney does not sift through a molecule, discharging it through urine, it might be wiped out by the liver, which utilizes macrophages to look for and dispose of remote bodies.1

Specialists have built peptide nanoparticles to outflank the organic framework and focus on the kidney cells. The advancement may demonstrate basic to tending to endless kidney infection. To date, there have been couple of answers for cutting edge kidney illness past dialysis and kidney transplant – both of which are amazingly costly and saddling. Already, specialists would likewise need to endorse substantial measurements of solution as they trusted a portion of the drug would have the capacity to reach and focus on the kidney. Be that as it may, this substantial dosing effectually affected different organs in the body.

While focused on drug delivery has for quite some time been a territory of fixation for malignancy inquire about, nanoparticles for focused medication conveyance for the kidneys has to a great extent gone unexplored. Basically, the specialists took a while to make their kidney focusing on molecule. This nanoparticle is a Michelle, which is 10-20 times littler than a conventional nanoparticle. This specific Michelle is blended from a peptide chain that is detailed from lysine and glutamic acids. The additional little size of the nanoparticle permits section into the kidneys through the underlying obstruction of kidney filtration while the peptide permits the nanoparticle to remain in the kidneys and conceivably empty a medication at the site of the malady without getting expelled by the urine. Thus, the scientists are exploiting a characteristic instrument of the body to focus on the kidneys and can limit fundamental off-target symptoms that are trademark to most kidney drugs.2

The scientists infused mice with fluorescent-marked nanoparticles. They found that the nanoparticles they had built were more present in the kidney than different parts of the body. These particles therefore could convey sedates more specifically than past tests by different scientists. Besides, these biocompatible, bio-degradable particles could get out of the body in under multi week and would not harm different organs.