Animal Use Alternatives
Models, Animal
Disease Models, Animal
Encyclopedias as Topic
Depression
Antidepressive Agents
Depressive Disorder, Major
Depressive Disorder
Efficacy of herpes simplex virus thymidine kinase in combination with cytokine gene therapy in an experimental metastatic breast cancer model. (1/9364)
Immunotherapy in combination with suicide gene therapy for breast cancer was tested using a metastatic animal model. Subcutaneous injection of the nonimmunogenic breast cancer cell line 4T1 in BALB/C mice gave rise to tumors in 100% of mice with both micrometastases and macrometastases in the lung. We used the herpes simplex virus thymidine kinase (HSV-TK) gene along with the cytokine genes granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) to determine their effect on tumor regression and inhibition of lung metastasis. Adenoviral (AV) vectors carrying these transgenes, in separate constructs, were used in this study. Intratumoral administration of AV-TK followed by 10 days of ganciclovir treatment resulted in a delay in tumor growth and, in some cases, in a low to moderate reduction in tumor volume. Inclusion of either GM-CSF or IL-2 gene with HSV-TK resulted in a slightly greater reduction in tumor volume, although these data were not significantly different from those obtained for TK treatment alone. However, when both cytokine genes were combined with TK, a substantial reduction in tumor growth was observed compared with HSV-TK alone (P < .02). Tumor weight data also exhibited superior efficacy of TK/GM-CSF/IL-2 treatment when compared with animals treated with TK gene only (P < .01). More importantly, TK/GM-CSF/IL-2 combination gene therapy induced a significant reduction in lung metastasis compared with any other treatment groups in the 4T1 model (P < .001 between TK GM-CSF/IL-2 versus TK only). Surgical excision of primary tumors after TK/GM-CSF/IL-2 plus ganciclovir treatment resulted in anti-metastatic activity that was similar to that observed for animals in which no surgery was performed. Survival analysis showed a significant difference between animals treated with AV-TK/GM-CSF/IL-2 and animals treated with TK only at 35 days after virus injection (P < .01). Immunophenotypic data suggest infiltration of lymphocytes within the tumor microenvironment in TK- and cytokine gene-treated animals. Thus, the overall data presented here demonstrate that TK gene therapy in combination with GM-CSF and IL-2 gene-mediated immunotherapy strategies have important implications in the treatment of breast cancer. (+info)Primary cultured hepatocytes of the bony fish, Oreochromis mossambicus, the tilapia: a valid tool for physiological studies on IGF-I expression in liver. (2/9364)
In spite of the importance of IGF-I for growth and development, knowledge about regulation of its production in submammalian species is rather limited. In order to create a tool for investigation of direct regulatory effects on the expression of IGF-I in bony fish liver, a primary cell culture of hepatocytes from Oreochromis mossambicus, the tilapia, was established. The cells were viable for up to 3 days and IGF-I mRNA synthesis was detected by northern blot and semiquantitative reverse transcriptase (RT)-PCR. Northern blot analysis of the primary cultured hepatocytes revealed four different IGF-I transcripts, 0.5, 1.9, 3.9 and 6.0 kb in size, which were identical to those in liver tissue. However, the expression rate was weaker than that in liver. The direct effects of recombinant tilapia (rt) growth hormone (GH) and salmon (s) IGF-I on the expression of IGF-I in primary cultured hepatocytes were investigated in time-course and dose-response experiments. In untreated cultures, IGF-I mRNA decreased with time. Hepatocytes treated with 100 nM rtGH resulted in a pronounced stimulation of IGF-I mRNA expression throughout the experiment. Treatment with rtGH in concentrations ranging from 0.1 nM to 1 microM caused a clear dose-dependent increase in the amount of IGF-I mRNA. Significant stimulation was obtained even with 0.1 nM, reaching a plateau with 10 nM. Neither significant inhibitory nor stimulatory effects were detected by adding sIGF-I from 0.1 nM to 1 microM to the hepataocytes. Our results indicate that the established primary cell culture of tilapia hepatocytes is a useful system in which to study direct effects of potential regulators of bony fish liver cell function. (+info)Exclusive androgenic effect of dehydroepiandrosterone in sebaceous glands of rat skin. (3/9364)
In order to analyze the hormonal effects of dehydroepiandrosterone (DHEA) in skin sebaceous glands, the precursor steroid was administered to ovariectomized (OVX) female Sprague-Dawley rats at a dose of 30 mg applied on the dorsal skin, twice daily, for 3, 6 and 12 months. In a parallel experiment, female OVX rats were treated with DHEA at the same daily percutaneous dose of 30 mg, alone or in combination with the antiandrogen Flutamide or the pure antiestrogen EM-800, for 12 months, in order to determine the androgenic and/or estrogenic components of DHEA action. Treatment of female OVX rats with DHEA resulted in a similar mild to moderate hyperplasia of the sebaceous glands of both dorsal (site of application) and ventral skin, as illustrated by an increase in the number and size of the acini. The above-indicated effects were observed at all time intervals studied, beginning at 3 months of treatment, and they were not further increased after longer term administration of DHEA (for 6 and 12 months). The addition of Flutamide to DHEA treatment completely prevented the DHEA-induced changes in the sebaceous glands, whereas the antiestrogen EM-800 had no effect. The present data indicate an exclusive androgenic stimulatory action of DHEA on the sebaceous glands, thus pointing out the importance of local intracrine DHEA transformation into androgens for skin anatomical integrity and function, while showing that estrogens, if active in rat skin, do not originate from DHEA. (+info)Electrophysiological and cardiohemodynamic effects of AH-1058, a new type calcium channel blocker, assessed by the in vivo canine model. (4/9364)
AH-1058 (4-(5H-dibenzo[a, d]cyclohepten-5-ylidene)- 1-[(E)-3-(3-methoxy-2-nitro)phenyl-2-propenyl]piperidine hydrochloride) is a novel calcium channel blocker whose chemical structure is quite different from those of typical calcium channel blockers. In this study, electrophysiological and hemodynamic effects of AH-1058 were assessed in the halothane-anesthetized, closed-chest canine model. Intravenous administration of a canine antiarrhythmic dose of 100 microg/kg of AH-1058 (n = 6) did not affect the cardiovascular variables, except that the cardiac output was decreased at 30 min after the drug administration. Additional administration of 200 microg/kg of AH-1058 (n = 6) suppressed the sinus nodal automaticity, AV nodal conduction and ventricular contraction and decreased the mean blood pressure, cardiac output and double product. The effects gradually appeared, while no change was detected in the intraventricular conduction, ventricular repolarization period, ventricular effective refractory period, preload to the left ventricle and total peripheral vascular resistance during the observation period of 30 min. The cardiosuppressive effects of AH-1058 can be explained by its calcium channel blocking action demonstrated in a previous in vitro experiment, while the lack of the effect on the vascular resistance would suggest that AH-1058 may become a slow-acting cardioselective calcium channel blocker. (+info)The effect of the prostaglandin I2 analogue OP-2507 on adrenaline-induced pulmonary edema in rabbits and analysis of hemodynamic changes. (5/9364)
This study was carried out to understand the onset mechanism of adrenaline (ADR)-induced pulmonary edema (PE) and the effect of drugs related to the arachidonate cascade in a rabbit model. ADR was administered intravenously by a bolus injection to the rabbits at 50, 75 and 100 microg/kg. To evaluate the severity of PE, the lung-water ratio (LWR) was calculated as a ratio of the difference between wet and dry lung weight to dry lung weight. The PE incidence and LWR exhibited a dose-dependent increase, and LWR correlated with the left atrial pressure (LAP). The involvement of the arachidonate cascade was evaluated by the co-administration of flurbiprofen, a cyclooxygenase inhibitor; ozagrel, a thromboxane synthase inhibitor; and OP-2507 (15-cis-(4-n-propylcyclohexyl)-6,17,18, 19,20-pentanor-9-deoxy-6,9-alpha-nitriloprostaglandin F1 methyl ester), a prostaglandin I2 analogue. Co-treatment of the rabbits with ADR and flurbiprofen resulted in an increase in LAP and the incidence of PE, whereas co-administration of ozagrel did not exhibit any significant changes in the measured parameters. Conversely, OP-2507 reduced the LAP, PE incidence and LWR when co-administered with ADR. Rabbits co-treated with OP-2507 displayed an improved cardiac function. The results of these studies demonstrated the effectiveness of OP-2507 in protecting the lung and cardiac function from the ADR-induced PE. (+info)Standardized ejection fraction as a parameter of overall ventricular pump function. (6/9364)
To evaluate the pump function of the ventricle, a parameter which (i) incorporates systolic and diastolic function and (ii) separates the heart from preload and afterload is needed. This study utilized ejection fraction (EF), calculated from the end-systolic (ES) and end-diastolic (ED) pressure-volume relationship (PVR) using an arbitrary set of loading conditions. Ten isolated canine hearts with a balloon placed inside the left ventricle were used to determine the ESPVR and EDPVR. An end-diastolic volume (EDV) at a pressure of 15 mmHg and an end-systolic volume (ESV) at 70 mmHg were obtained from the EDPVR and ESPVR, respectively. EF was calculated as (EDV-ESV)/EDV. With low-dose (8 microg/min) and high-dose (40 microg/min) dobutamine infusion, the EF increased from 0.25+/-0.16 to 0.33+/-0.13 and 0.57+/-0.08 (p<0.01), respectively, in conjunction with increases in end-systolic elastance from 3.11+/-0.83 to 3.48+/-1.08 and 5.38+/-1.91 mmHg/ml (p<0.01). It was thus concluded that because the estimation of EF separates the heart from preload and afterload, this method may facilitate comparing overall pump function of hearts beating under different loading conditions. (+info)Carnosine as a potential anti-senescence drug. (7/9364)
The naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) has been found to exert an anti-senescence effect when used as a dietary supplement. Carnosine clearly improved the external appearance of experimental animals and provided beneficial physiological effects, thus maintaining the animals in better condition than control animals receiving no carnosine or a mixture of beta-alanine and L-histidine. (+info)DNA vaccines. (8/9364)
DNA vaccination or genetic immunization is a rapidly developing technology that offers new approaches for the prevention and therapy of disease. Regarding the inoculation method of DNA vaccine, we recommend the gene gun delivery system, which is a highly reliable method compared to intramuscular inoculation. DNA vaccines could have potential advantages over other types of vaccines in that these vaccines can induce strong cellular immune responses, cytotoxic T lymphocytes and type 1 helper T cells, without resorting to live organisms or complicated protein formulation. The cellular immune responses are especially required for the protection against infections with intracellular pathogens such as viruses and Mycobacterium tuberculosis and protection against cancers, suggesting that they seem to be suitable targets of DNA vaccines. We describe here that their application to bacterial infections requires optimization of codon usage in the DNA vaccines to the host animal to improve translational efficiencies of the bacteria genes. DNA vaccines for a variety of pathogens and cancers have now entered phase I/II human clinical trials. (+info)"Animal Use Alternatives" refers to the methods and techniques used in scientific research, testing, and education that avoid or reduce the use of animals. The three main categories of alternatives are:
1. Replacement: This involves using non-animal methods to entirely replace the use of animals in a particular procedure or experiment. Examples include the use of computer modeling, cell cultures, and tissue samples instead of live animals.
2. Reduction: This refers to methods that reduce the number of animals used in a given procedure or experiment while still achieving the same scientific objective. Examples include using statistical methods to design experiments that require fewer animals, or sharing data and resources between research groups.
3. Refinement: This involves modifying procedures to minimize suffering and improve animal welfare for those animals that are still used. Examples include using anesthesia and pain relief during surgical procedures, providing appropriate housing and enrichment, and implementing humane endpoints in experiments.
The development and implementation of animal use alternatives is a key goal in the ethical and responsible conduct of scientific research, testing, and education.
An animal model in medicine refers to the use of non-human animals in experiments to understand, predict, and test responses and effects of various biological and chemical interactions that may also occur in humans. These models are used when studying complex systems or processes that cannot be easily replicated or studied in human subjects, such as genetic manipulation or exposure to harmful substances. The choice of animal model depends on the specific research question being asked and the similarities between the animal's and human's biological and physiological responses. Examples of commonly used animal models include mice, rats, rabbits, guinea pigs, and non-human primates.
Animal disease models are specialized animals, typically rodents such as mice or rats, that have been genetically engineered or exposed to certain conditions to develop symptoms and physiological changes similar to those seen in human diseases. These models are used in medical research to study the pathophysiology of diseases, identify potential therapeutic targets, test drug efficacy and safety, and understand disease mechanisms.
The genetic modifications can include knockout or knock-in mutations, transgenic expression of specific genes, or RNA interference techniques. The animals may also be exposed to environmental factors such as chemicals, radiation, or infectious agents to induce the disease state.
Examples of animal disease models include:
1. Mouse models of cancer: Genetically engineered mice that develop various types of tumors, allowing researchers to study cancer initiation, progression, and metastasis.
2. Alzheimer's disease models: Transgenic mice expressing mutant human genes associated with Alzheimer's disease, which exhibit amyloid plaque formation and cognitive decline.
3. Diabetes models: Obese and diabetic mouse strains like the NOD (non-obese diabetic) or db/db mice, used to study the development of type 1 and type 2 diabetes, respectively.
4. Cardiovascular disease models: Atherosclerosis-prone mice, such as ApoE-deficient or LDLR-deficient mice, that develop plaque buildup in their arteries when fed a high-fat diet.
5. Inflammatory bowel disease models: Mice with genetic mutations affecting intestinal barrier function and immune response, such as IL-10 knockout or SAMP1/YitFc mice, which develop colitis.
Animal disease models are essential tools in preclinical research, but it is important to recognize their limitations. Differences between species can affect the translatability of results from animal studies to human patients. Therefore, researchers must carefully consider the choice of model and interpret findings cautiously when applying them to human diseases.
An encyclopedia is a comprehensive reference work containing articles on various topics, usually arranged in alphabetical order. In the context of medicine, a medical encyclopedia is a collection of articles that provide information about a wide range of medical topics, including diseases and conditions, treatments, tests, procedures, and anatomy and physiology. Medical encyclopedias may be published in print or electronic formats and are often used as a starting point for researching medical topics. They can provide reliable and accurate information on medical subjects, making them useful resources for healthcare professionals, students, and patients alike. Some well-known examples of medical encyclopedias include the Merck Manual and the Stedman's Medical Dictionary.
Depression is a mood disorder that is characterized by persistent feelings of sadness, hopelessness, and loss of interest in activities. It can also cause significant changes in sleep, appetite, energy level, concentration, and behavior. Depression can interfere with daily life and normal functioning, and it can increase the risk of suicide and other mental health disorders. The exact cause of depression is not known, but it is believed to be related to a combination of genetic, biological, environmental, and psychological factors. There are several types of depression, including major depressive disorder, persistent depressive disorder, postpartum depression, and seasonal affective disorder. Treatment for depression typically involves a combination of medication and psychotherapy.
Antidepressive agents are a class of medications used to treat various forms of depression and anxiety disorders. They act on neurotransmitters, the chemical messengers in the brain, to restore the balance that has been disrupted by mental illness. The most commonly prescribed types of antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). These medications can help alleviate symptoms such as low mood, loss of interest in activities, changes in appetite and sleep patterns, fatigue, difficulty concentrating, and thoughts of death or suicide. It is important to note that antidepressants may take several weeks to reach their full effectiveness and may cause side effects, so it is essential to work closely with a healthcare provider to find the right medication and dosage.
Major Depressive Disorder (MDD), also simply referred to as depression, is a serious mental health condition characterized by the presence of one or more major depressive episodes. A major depressive episode is a period of at least two weeks during which an individual experiences a severely depressed mood and/or loss of interest or pleasure in nearly all activities, accompanied by at least four additional symptoms such as significant changes in appetite or weight, sleep disturbances, psychomotor agitation or retardation, fatigue or loss of energy, feelings of worthlessness or excessive guilt, difficulty thinking, concentrating, or making decisions, and recurrent thoughts of death or suicide.
MDD can significantly impair an individual's ability to function in daily life, and it is associated with increased risks of suicide, substance abuse, and other mental health disorders. The exact cause of MDD is not fully understood, but it is believed to result from a complex interplay of genetic, biological, environmental, and psychological factors. Treatment typically involves a combination of psychotherapy (such as cognitive-behavioral therapy) and medication (such as selective serotonin reuptake inhibitors or tricyclic antidepressants).
A depressive disorder is a mental health condition characterized by persistent feelings of sadness, hopelessness, and loss of interest or pleasure in activities. It can also include changes in sleep, appetite, energy levels, concentration, and self-esteem, as well as thoughts of death or suicide. Depressive disorders can vary in severity and duration, with some people experiencing mild and occasional symptoms, while others may have severe and chronic symptoms that interfere with their ability to function in daily life.
There are several types of depressive disorders, including major depressive disorder (MDD), persistent depressive disorder (PDD), and postpartum depression. MDD is characterized by symptoms that interfere significantly with a person's ability to function and last for at least two weeks, while PDD involves chronic low-grade depression that lasts for two years or more. Postpartum depression occurs in women after childbirth and can range from mild to severe.
Depressive disorders are thought to be caused by a combination of genetic, biological, environmental, and psychological factors. Treatment typically involves a combination of medication, psychotherapy (talk therapy), and lifestyle changes.
According to the World Health Organization (WHO), "An attempted suicide is a non-fatal self-directed, potentially injurious behavior with intent to die as a result of the behavior. It's a clear expression of intention to die."
It's important to note that anyone who has attempted suicide requires immediate professional medical attention and support. They should be assessed for their level of suicidal ideation and any underlying mental health conditions, and provided with appropriate care and treatment. If you or someone you know is struggling with thoughts of suicide, please reach out to a healthcare provider or a trusted mental health professional immediately.
Suicide is defined in the medical field as the intentional taking of one's own life. It is a complex phenomenon with various contributing factors, including psychological, biological, environmental, and sociocultural elements. Suicide is a significant global public health concern that requires comprehensive understanding, prevention, and intervention strategies. If you or someone you know is struggling with thoughts of self-harm or suicide, it's essential to seek help from a mental health professional immediately.