Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential involvement of apoptosis in the pathogenesis of visceral leishmaniasis (VL) was examined by studying spontaneous and Leishmania antigen (LAg)-induced apoptosis using cryopreserved peripheral blood mononuclear cells (PBMC) of Sicilian patients with VL. Results indicate that monocytes and T lymphocytes from acute VL patients show a significantly higher level of apoptosis compared with that observed in healed subjects. The percentage of apoptotic cells was higher in monocytes than in T lymphocytes. T cells involved in programmed cell death (PCD) were mainly of the CD4(+) phenotype. In particular, the T helper 1-type (Th1) subset, as evaluated by chemokine receptor-5 (CCR5) expression, is involved in this process. Cell death in Th1-type uses a CD95-mediated mechanism. Furthermore, Th1-type CCR5(+) cells are prone to cell suicide in an autocrine or paracrine way, as attested by enhanced expression of CD95L in acute VL patients. The reduction in Th1-type cells by apoptosis was confirmed by the decrease in interferon-gamma secretion. In conclusion, apoptosis of monocytes, CD4(+) and CD4(+) CCR5(+) T cells could be involved in the failure of cell mediated immunity that is responsible for severe immune-depression in VL.
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PMID:CD4+ CCR5+ and CD4+ CCR3+ lymphocyte subset and monocyte apoptosis in patients with acute visceral leishmaniasis. 1537 87

Antimony (Sb) is the mainstay for the treatment of Leishmaniasis. It has serious, often lethal, cardiovascular side effects. The objective of this study was to examine the effects of Sb treatment upon the electrocardiogram (ECG), myocyte contractility (assessed by monitoring sarcomere length during field stimulation), whole-cell action potential (AP) and calcium current (I(Ca)) of the guinea-pig and to evaluate L-carnitine as a cardioprotective agent. Guinea-pigs received daily injections of either saline, Sb(V), Sb(III), L-carnitine or L-carnitine with Sb(III). Eight lead ECGs were recorded under halothane anaesthesia every 4 days. At the end of each treatment regime, animals were killed and ventricular myocytes were enzymatically isolated. Treatment with Sb(V) for 26 days prolonged the QT interval of the ECG. Treatment with Sb(III) was lethal within 2 days for approximately 50% of the animals. The survivors showed ECG alterations similar to those described in man: T wave flattening and/or inversion, depression of the ST segment, and elongation of RR and QT intervals. Their ventricular myocytes showed impaired contraction responses to changes in stimulus frequency, elongated AP and reduced I(Ca). Combined treatment with L-carnitine and Sb(III) delayed mortality. Prior treatment with L-carnitine followed by combined treatment with L-carnitine and Sb(III) reduced mortality to <10% over 12 days and these animals showed normal ECG. Their myocytes showed normal contractility and AP. It is concluded that L-carnitine has a preventive cardioprotective role against antimony-induced cardiomyopathy. The mechanism of action of L-carnitine may be to counter oxidative stress caused by Sb(III).
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PMID:Antimony-induced cardiomyopathy in guinea-pig and protection by L-carnitine. 1564 65

Binding of the interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) triggers a series of intracellular events culminating in lymphocyte proliferation and differentiation. We report here the identification of a novel G245R polymorphism in the membrane proximal domain of the IL-2 receptor beta chain (IL-2Rbeta). Present at a frequency of 7.2%, the IL-2-Rbeta G245R was identified in a population of Eastern Sudan exposed to a severe outbreak of visceral leishmaniasis (VL), a disease associated with a marked depression of T-cell antigen-specific responses. The location of the G245R polymorphism next to the box1/box2 proximal cytokine receptor homology segment and suggestive genetic association with the development of disease (P=0.043), suggest that it may affect Janus kinase (JAK) association and impair growth signal transduction. However, additional genetic association with a synonymous single nucleotide polymorphism (IL2RB+8777T) suggests that other variations of IL2RB or nearby genes participate in the highly significant linkage with VL at 22q12 previously reported for this population.
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PMID:Identification of a novel G245R polymorphism in the IL-2 receptor beta membrane proximal domain associated with human visceral leishmaniasis. 1710 90

A 4-year-old, domestic shorthair, female spayed cat was presented for decreased appetite and depression. Severe pancytopenia with erythrocyte autoagglutination was found. The cat was seronegative for feline immunodeficiency and leukemia viruses. Immune-mediated hemolytic anemia was suspected but no response to treatment with a blood transfusion, enrofloxacin, and prednisone was observed. Blood and bone marrow smears obtained 11 days later contained Leishmania amastigotes in the cytoplasm of neutrophils and macrophages, respectively. Serologic and PCR testing of peripheral blood confirmed infection with Leishmania infantum. Despite treatment, the cat worsened clinically and was euthanized. At necropsy, visceral dissemination of the parasite was confirmed. The findings in this case indicate that visceral leishmaniasis should be considered as a differential diagnoses in cats with pancytopenia in areas endemic for Leishmania. In addition, amastigotes may be observed in peripheral blood neutrophils.
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PMID:Pancytopenia in a cat with visceral leishmaniasis. 1949 May 73

Opportunistic infections (OIs) are the leading cause of mortality and morbidity among HIV-positive subjects. The breadth of reports of the rare occurrence of OIs in HIV/AIDS has been increasing over the years and more recent studies have outlined the changing trends in the emergence of newer pathogens. Recent reports of the association of certain protozoans that normally do not infect sites other than their normal sites of localization have generated huge interest among scientists. The complete depression of the immune system, followed by the onset of OIs, especially due to protozoans, i.e. toxoplasmosis, isosporiasis, leishmaniasis, cyclosporosis, microsporidiosis and cryptosporidiosis, is not uncommon in AIDS. The immunologic and pathologic basis behind the susceptibility of immunodepressed individuals to these 'non-site-specific parasites' is likely to have a huge impact on HIV disease progression. Certain possible shortcomings in the immunologic armory of immunodeficient subjects, their failure to contain the establishment of these 'uncommon' agents in the human host and their significance in HIV disease progression are discussed.
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PMID:Common protozoans as an uncommon cause of respiratory ailments in HIV-associated immunodeficiency. 1970 77

Acid sensing ion channels (ASICs) are implicated in various brain functions including learning and memory and are involved in a number of neurological disorders such as pain, ischemic stroke, depression, and multiple sclerosis. We have recently defined ASICs as one of receptor targets of aromatic diamidines in neurons. Aromatic diamidines are DNA-binding agents and have long been used in the treatment of leishmaniasis, trypanosomiasis, pneumocystis pneumonia and babesiosis. Moreover, some aromatic diamidines are used as skin-care and baby products and others have potential to suppress tumor growth or to combat malaria. A large number of aromatic diamidines or analogs have been synthesized. Many efforts are being made to optimize the therapeutic spectrum of aromatic diamidines, i.e. to reduce toxicity, increase oral bioavailability and enhance their penetration of the blood-brain barrier. Aromatic diamidines therefore provide a shortcut of screening for selective ASIC inhibitors with therapeutic potential. Intriguingly nafamostat, a protease inhibitor for treating acute pancreatitis, also inhibits ASIC activities. Aromatic diamidines and nafamostat have many similarities although they belong to distinct classes of medicinal agents for curing different diseases. Here we delineate background, clinical application and drug development of aromatic diamidines that could facilitate the screening for selective ASIC inhibitors for research purposes. Further studies may lead to a drug with therapeutic value and extend the therapeutic scope of aromatic diamidines to combat neurological diseases.
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PMID:Design and screening of ASIC inhibitors based on aromatic diamidines for combating neurological disorders. 2085 10

Visceral leishmaniases are vector-borne parasitic diseases caused by protozoa belonging to the genus Leishmania. The heterogeneity of clinical manifestations and epidemiological characteristics of the disease reflect the complex interplay between the infecting Leishmania species and the genetic and immunologic characteristics of the infected host. The clinical presentation of visceral leishmaniasis depends strictly on the immunocompetency of the host and ranges from asymptomatic to severe forms. Conditions of depression of the immune system, such as HIV infection or immunosuppressive treatments, impair the capability of the immune response to resolve the infection and allow reactivation and relapses of the disease.
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PMID:Visceral leishmaniasis: host-parasite interactions and clinical presentation in the immunocompetent and in the immunocompromised host. 2338 Apr 19

Intracellular pathogenic protozoan infection like visceral leishmaniasis is considered in terms of the overall inflammatory response and the complex cellular interactions leading to formation of the activated macrophage. Analysis of the development of activation is facilitated when operationally defined stage of activation are characterized using a library of objective markers. There is a role of arginase in the immune response supporting its involvement in macrophage effector mechanism in vitro and in vivo. 5'-Nucleotidase a plasma membrane component has been cited as a biochemical correlate of macrophage function in an altered morphological and biochemical state of activation and stimulation. Depression in 5'-nucleotidase activity has been generally referred to as a characteristic marker of activated macrophages. Lysozyme or lysosomal enzymes are released into the endocytic or autophagic vacuole macrophage where they serve the purpose of intracellular digestion of engulfed or segregated materials. In the present study, we have studied levels of arginase and 5'-nucleotidase (marker for macrophage activation) in monocytes of active VL patients and healthy controls. Lysozyme a secretary product of macrophages was also measured in supernatants collected from monocytes of active VL patients and healthy controls. Elevated levels of 5'-nucleotidase were observed in supernatants of monocytes from active VL patients as compared to healthy controls. Low levels of arginase and lysozyme production by monocytes isolated from VL patients were observed as compared to healthy controls. Our studies suggest that low levels of arginase and elevated 5'-nucleotidase activity could be one of the mechanisms in the pathology of VL infection. Low lysozyme activity in patients may account for persistence of Leishmania parasites in VL infections.
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PMID:Studies on the arginase, 5'-nucleotidase and lysozyme activity by monocytes from visceral leishmaniasis patients. 2354 35

Leishmaniasis comprises a group of diseases caused by a protozoan parasite belonging to the genus Leishmania and transmitted by the bite of infected female sand flies. Leishmaniasis is endemic in 88 countries and causes significant morbidity and mortality worldwide. Phenomena such as globalization and human migration, as well as the increased volume of international travel have extended its prevalence in developed countries. In addition, the incidence of leishmaniasis as an opportunistic disease has increased in recent years because of the growing number of patients with immune depression secondary to chronic illness, neoplasm, transplant and HIV infection, thereby constituting a public health problem. In humans, there are three possible clinical syndromes of leishmaniasis: cutaneous, mucocutaneous and visceral. Mucocutaneous disease is due to extension of local skin disease into the mucosal tissue via direct extension, bloodstream or lymphatics. Lesions interest mainly the oral and nasal mucosa and occasionally the laryngeal and pharyngeal mucosa. If not recognized and adequately treated, MCL may disfigure the patient because of the chronic local destruction of tissue of the nose, pharynx and palate. Because of the invariable involvement of the areas pertaining otorhinolaryngologists, it is important for ENT specialists and family physicians to have awareness of this condition and its clinical manifestations, particularly in presence of a history positive for travel to endemic areas. If mucocutaneous leishmaniasis is suspected, otorhinolaryngologic examination is very helpful in establishing a correct diagnosis, preventing inappropriate treatment.
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PMID:Ear, nose and throat manifestations of mucocutaneous Leishmaniasis: a literature review. 2489 64

Caused by Trypanosoma cruzi, Chagas disease is responsible for public health problems greater in magnitude than those attributed to malaria, schistosomiasis, or leishmaniasis. A factor in the socioeconomic development of poor countries, Chagas disease can cause death due to a high parasitic burden during its acute phase due and irreversible damage in organs such as the heart, esophagus, and colon during its chronic phase, even when the number of parasites is minimal. For treating Chagas disease, benznidazole (BNZ) remains the drug of choice and, in Latin America, the only drug on the market for treating the disease. However, BNZ has exhibited insufficient activity in the chronic phase of Chagas disease, required administration in large doses, prolonged treatment, and shown a high incidence of adverse reactions (vomiting, rash, peripheral neuropathy, and spinal cord depression), toxicity, and low solubility in water. As an antidote, pharmaceutical technologies have been introduced that can improve BNZ's solubility and dissolution, as well as reduce side effects in light of its bioavailability, all of which can enhance therapy for Chagas disease. In response to that trend, by conducting a literature review, we sought to identify current pharmaceutical technologies used in tandem with BNZ to improve therapy for Chagas disease. Documented techniques include emulsion and microemulsion formation, solutions, parenteral formulas, micronization, and drug delivery systems supported by the development of nanoparticles and cyclodextrins, solid dispersions, and the use of metal-organic frameworks as innovative excipients. Such technologies increase the water solubility of BNZ by 4-25-fold on dissolution and an 85% release with efficacy in only a few minutes, as recorded during a viability experiment with nanoparticle suspensions. That experiment demonstrated the need for a lower concentration of BNZ to kill 50% of trypomastigote forms of T. cruzi, described in terms of the formation of BNZ-cyclodextrin complexes, and modulating and vectoring of the antichagasic by using metal-organic frameworks. Altogether, the promising results of research identified can enable strategies to improve solubility and efficacy of BNZ, as well as therapy for Chagas disease.
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PMID:Technological innovation strategies for the specific treatment of Chagas disease based on Benznidazole. 2945 13


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