Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085631 (agitation)
 12,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The loss of biological activity upon heating or agitation of human interferons is markedly altered by changing their aqueous environment. Low pH significantly stabilizes liquid fibroblast interferon at 68 degrees C and 37 degrees C whereas chaotropic salts stabilize at 68 degrees C but not at 37 degrees C; this anomalous result may be due to reactivation of biological activity at the higher temperature. The concentration of extraneous proteins influences the apparent thermal stability at any temperature and pH; thus, interferon was not stable even at low pH at protein concentrations less than 5 microgram/ml. Solutions of partially purified fibroblast interferon can be inactivated by mechanical stress; the addition of proteins or nonionic detergents prevents such inactivation. Freeze-dried preparations show the greatest thermal stability. The use of high-temperature, accelerated storage tests makes it possible to predict the shelf-life of freeze-dried interferon.
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PMID:Thermal and vortical stability of purified human fibroblast interferon. 3 70

Interferon derived from human fibroblasts is readily inactivated during agitation and filtration. This inactivation has been shown to be largely a product of mechanical stress, and has been studied in detail by subjecting interferon to controlled shear stress using a rotational viscometer. The possible mechanism of this phenomenon is discussed.
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PMID:The mechanism of the inactivation of human fibroblast interferon by mechanical stress. 89 66

Ten (17%) of 58 patients with chronic viral hepatitis treated with a four- to 12-month course of recombinant human interferon alfa developed psychiatric side effects. The psychiatric side effects fell into three categories: an organic personality syndrome characterized by irritability and short temper; an organic affective syndrome marked by extreme emotional lability, depression, and tearfulness; and a delirium marked by clouding of consciousness, agitation, paranoia, and suicidal potential. These psychiatric side effects appeared after one to three months of therapy, usually improved within three to four days of decreasing the dose of interferon alfa, and invariably resolved once therapy was stopped. The organic personality and affective syndromes tended to occur in patients who received the highest dose of interferon alfa, who had relatively mild hepatitis, and who lost weight during interferon treatment. Delirium tended to occur in patients with severe hepatitis who had previous evidence of organic brain injury or dysfunction or previous drug and alcohol abuse. Failure to recognize these side effects quickly and to treat them with supportive therapy and modification of the dose of interferon alfa could result in limitation of therapy and serious personal and interpersonal consequences.
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PMID:Psychiatric complications of long-term interferon alfa therapy. 330 72

Six marrow transplant recipients receiving acyclovir at various dosages for herpesvirus infections developed neurologic symptoms during treatment. Three were receiving concomitant human alpha interferon, and all six had received previous intrathecal methotrexate. Symptoms developed a median of 8 days (range, 2 to 18 days) after initiation of therapy and consisted of lethargy or agitation in five patients, tremor in five, and disorientation or transient hemiparesthesias in one patient each. The only consistent laboratory finding was an abnormal electroencephalogram. Five patients had an increased myelin basic protein level in cerebrospinal fluid. Improvement or resolution of symptoms occurred a median of 13 days (range, 4 to 15 days) after cessation of acyclovir therapy. Acyclovir used at a wide range of dosages may be associated with reversible neurologic symptoms in patients after marrow transplantation. The contribution of previous prophylaxis for central nervous system leukemia, herpesvirus infections, marrow transplantation, or the concomitant use of interferon is unknown.
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PMID:Neurologic symptoms associated with parenteral acyclovir treatment after marrow transplantation. 630 45

Parameters of physical constituents of the agitation process and mass-exchange characteristics of the suggested bioreactor for suspension cultivation of pig splenocytes are determined. The effect of hydrodynamic conditions on viability and interferon-synthesizing activity of cells in production of alpha-interferon of pigs has been studied. The relation existing between interferonogenesis processes proceeding under suspension and under stationary biosynthesis has been analyzed by the pair correlation method.
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PMID:[The effect of hydrodynamic conditions on the interferon-synthesizing activity of swine splenocytes in the production of alpha-interferon]. 765 59

It has recently been published the results of a prospective, comparative study for adjuvant chemotherapy of 164 colorectal cancer patients. Pathological stages were Dukes B 79, C 85 of the cases. The site of primary tumour was colon 108, rectum 56 of the patients. The treatment protocols were as follows: 425 mg/m2 5-fluorouracil plus 20 mg/m2 leucovorin on days 1-5 at 28 days cycles six times (LV group). The IFN group received the same chemotherapy completed with weekly 3 x 3 MIU interferon alpha. Both treatment groups were well balanced. The mean follow up time was 38.1 months. There were 91 patients of relapse and 65 deaths this time. The time to progression was 15 months in the LV group and 12.7 months in the IFN group (p < 0.05). The mean survival time was 24 months in the LV group compared to 22.3 of the IFN group. The frequency and sites of relapses did not differ statistically between the both groups. The preoperative CEA-level was elevated in 42 cases. The mean survival time was 26.4 months in the cases having normal CEA-level compared to 16.1 months of the cases with high-level (p < 0.001). The side-effects were transient and mild, while in the group treated with interferon were more instances of fever, fatigue, flu-like syndrome, psychic disorders, depression and agitation. The administration of interferon had to be interrupted in 4 cases. The results of interim analysis suggest choosing the so-called Mayo protocol for the standard adjuvant treatment of colorectal cancer.
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PMID:[Low-dose leucovorin and interferon-alpha as modulators of 5-fluorouracil for adjuvant chemotherapy of colorectal cancer]. 967 18

In the absence of surfactants, recombinant human growth hormone (rhGH) rapidly forms insoluble aggregates during agitation. The nonionic surfactant Tween 20, when present at Tween:protein molar ratios >4, effectively inhibits this aggregation. Differential scanning calorimetry (DSC) of rhGH solutions showed melting transitions that decreased by ca. 2 degrees C in the presence of Tween. Circular dichroism (CD) studies of the same thermal transition showed that the decrease is specific to the relatively high protein concentrations required for DSC. CD studies showed melting transitions that decreased with lower protein concentrations. Tween has an insignificant effect on the melting transition of rhGH at lower protein concentrations (0.18 mg/mL). Injection titration microcalorimetry showed that the interaction of Tween with rhGH is characterized by a weak enthalpy of binding. For comparison, interferon-g, another protein which has been shown to bind Tween, also shows weak enthalpy of binding. Fluorescent probe binding studies and infrared spectroscopic investigations of rhGH secondary structure support suggestions in the literature (Bam, N. B.; Cleland, J. L., Randolph, T. W. Molten globule intermediate of recombinant human growth hormone: stabilization with surfactants. Biotechnol. Prog. 1996. 12, 801-809) that Tween binding is driven by hydrophobic interactions, with little perturbation of protein secondary structure.
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PMID:Tween protects recombinant human growth hormone against agitation-induced damage via hydrophobic interactions. 1018 66

Recombinant preparations of the cytokine interferon (IFN)-alpha are increasingly used to treat a number of medical conditions, including chronic viral hepatitis and several malignancies. Although frequently effective, IFN alpha induces a variety of neuropsychiatric adverse effects, including an acute confusional state that develops rapidly after initiation of high-dose IFN alpha, a depressive syndrome that develops more slowly over weeks to months of treatment, and manic conditions most often characterised by extreme irritability and agitation, but also occasionally by euphoria. Acute IFN alpha-induced confusional states are typically characterised by disorientation, lethargy, somnolence, psychomotor retardation, difficulties with speaking and writing, parkinsonism and psychotic symptoms. Strategies for managing delirium should be employed, including treatment of contributing medical conditions, use of either typical or atypical antipsychotic agents and avoidance of medications likely to worsen mental status. Significant depressive symptoms occur in 21-58% of patients receiving IFN alpha, with symptoms typically manifesting over the first several months of treatment. The most replicated risk factor for developing depression is the presence of mood and anxiety symptoms prior to treatment. Other potential, but less frequently replicated, risk factors include a past history of major depression, being female and increasing IFN alpha dosage and treatment duration. The available data support two approaches to the pharmacological management of IFN alpha-induced depression: antidepressant pretreatment or symptomatic treatment once IFN alpha has been initiated. Pretreatment might be best reserved for patients already receiving antidepressants or for patients who endorse depression or anxiety symptoms of mild or greater severity prior to therapy. Several recent studies demonstrate that antidepressants effectively treat IFN alpha-induced depression once it has developed, allowing the vast majority of subjects to complete treatment successfully. Recent data suggest that IFN alpha-induced depression may be composed of two overlapping syndromes: a depression-specific syndrome characterised by mood, anxiety and cognitive complaints, and a neurovegetative syndrome characterised by fatigue, anorexia, pain and psychomotor slowing. Depression-specific symptoms are highly responsive to serotonergic antidepressants, whereas neurovegetative symptoms are significantly less responsive to these agents. These symptoms may be more effectively treated by agents that modulate catecholaminergic functioning, such as combined serotonin-noradrenaline (norepinephrine) antidepressants, bupropion, psychostimulants or modafinil. Additional factors to consider in selecting an antidepressant include potential drug-drug interactions and adverse effect profile. Finally, IFN alpha appears capable of inducing manic symptoms. Mania, especially when severe, is a clinical emergency. When this occurs, IFN alpha and antidepressants should be stopped, an emergency psychiatric consultation should be obtained, and treatment with a mood stabilizer should be initiated.
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PMID:Neuropsychiatric adverse effects of interferon-alpha: recognition and management. 1569 25

Interleukin-2 (IL-2) has been shown to produce durable complete remission in patients with renal cell carcinoma (RCC). A phase 2 study was conducted to evaluate the potential therapeutic synergy as well as the toxic side effects of the concurrent administration of IL-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with advanced stage disease. Twenty-one patients with unresectable or metastatic RCC having an Eastern Oncology Cooperative Group performance status of 0 or 1 were enrolled. Six patients had received prior immunotherapy with interferon (IFN)-alpha, IFN-gamma, and IL-12, whereas the remaining 15 subjects were previously untreated. Thirteen patients were assigned to a moderate-dose bolus of IL-2 at 72,000 IU/kg every 8 hours on days 1 through 5 and days 15 through 19, whereas 8 patients were given IL-2 as an intravenous continuous infusion at a dose of 5 MU/m2/d on days 1 through 5 and days 15 through 19. Subcutaneous GM-CSF at 125 microg/d on days 1 through 21 was administered concomitantly with IL-2. The median number of IL-2 bolus doses was 23 of a scheduled 28 (85%), whereas with the continuous infusion, 93% of planned IL-2 was given. All patients received 100% of GM-CSF doses. There were no complete or partial responses in this study. Of 13 patients treated in the bolus IL-2 arm, 10 had systemic progression of disease at 4 to 8 weeks, 1 developed metastasis in the brain at 4 weeks, and 2 had stable disease for 4 and 17 months. Among the 8 subjects treated with continuous infusion IL-2, 3 progressed with brain lesions at 3 to 8 weeks and 5 had stable disease at 6+, 7, 8+, 15+, and 17+ months. The median survival for the whole group was 10 months, with a range of 0.5 to 40+ months. There were no regimen-related deaths, and most of the observed toxicities were grade 1 and 2. Serious toxicities (grade 3 and 4) included anemia, atrial fibrillation, oliguria, abnormal liver function, and neurologic events like agitation or confusion. The combination of recombinant IL-2 and GM-CSF administered in the designed schedule and doses was not effective in patients with metastatic RCC and may even interfere with the therapeutic potential of moderate-dose IL-2 and increase its adverse events.
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PMID:A phase 2 study of moderate dose interleukin-2 and granulocyte-macrophage colony-stimulating factor in patients with metastatic or unresectable renal cell carcinoma. 1622 75

Interferon alfa2 (IFN-alpha2) is a parenterally administered cytokine used to treat patients with Hepatitis C and B, and malignancy. Interferon (INF) has a relatively high rate of central nervous system (CNS) adverse effects, including agitation, depression, fatigue, cognitive dysfunction, suicidal thought and drug craving. Using functional magnetic resonance imaging (fMRI) we studied patients with Hepatitis C virus (HCV) infection who were not more than mildly clinically depressed at baseline for their CNS reaction to IFN-alpha2. During fMRI, patients underwent visual stimulation with pictures designed to induce feelings of depression. In the two patients who became clinically depressed or markedly anxious while on treatment with interferon, but not in patients who did not experience these effects, there was a significant activation in specific areas of the brain known to be involved with depression, along with an increase above baseline in the Beck Depression Scale for the patient who developed INF-induced depression. The activation pattern differed from that previously observed for endogenous depression, indicating that INF-induced depression may differ in its underlying neuropathology. Functional magnetic resonance imaging can be an important tool in understanding and monitoring for (INF and other) medication-induced CNS effects, and response to treatment.
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PMID:Use of fMRI to predict psychiatric adverse effects of interferon treatment for Hepatitis C - preliminary report. 1930 May 95


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