Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alteration of growth of dimethylbenz[a]anthracene-induced mammary tumors was caused by removal of estrogen (ovariectomy), or insulin (diabetes), or by inhibition of prolactin secretin (treatment with an ergoline derivative). The levels of cyclic AMP (cAMP) and cGMP were measured in carcinomas classified as growing, static, and regressing. The amount of cAMP, expressed as pmoles/mg tumor weight or pmoles/mg protein, was lowest in growing tumors, intermediate in static tumors, and highest in those regressing. No correlation was seen between tumor growth and cGMP levels. Cyclophosphamide-induced tumor stasis did not elevate cAMP levels. The data suggest a role of cAMP in arrest of hormone-induced tumor growth.
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PMID:Relationship of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate to growth of dimethylbenz(a)anthracene-induced mammary tumors in rats. 17 3

Fifty-eight patients were treated with cefotaxime (CTX, Claforan) intravenously. Almost all patients (54 patients) had underlying diseases that were 16 cases of diabetes mellitus, 10 cases of respiratory diseases, 8 cases of cerebral vascular disturbance, 6 cases of renal diseases and blood diseases, 5 cases of carcinoma and hypertension, 4 cases of cholelithiasis, 3 cases of heart diseases and 7 cases of other diseases. The clinical efficacy of CTX in 34 cases of RTI, 11 cases of UTI, 8 cases of BTI and 5 cases of other infection was excellent in 11 cases, good in 27 cases, fair in 12 cases, poor in 4 cases and unclear in 4 cases. The over all clinical effectiveness was 70.4%. No adverse reaction was observed except for 2 cases (general fatigue in 1 case and eruption and itching in another). These results obtained should support the usefulness of CTX.
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PMID:[Clinical efficacy of cefotaxime in the field of internal medicine]. 632 49

Cyclophosphamide promoted the onset of overt diabetes in non-obese diabetes-prone mice of both sexes. Two injections of this agent at 2 weeks apart were necessary to obtain a constant high incidence, although even a single injection was effective in some animals. Clinical symptoms of the cyclophosphamide-induced diabetes were similar to those of the naturally occurring type. The same schedule of cyclophosphamide treatment failed to induce diabetes in non-diabetic mouse strains, such as DS/Shi,Jcl:ICR or in non-obese non-diabetes-prone mice, which suggests that the promotion of diabetes by cyclophosphamide in non-obese diabetes-prone mice is not due to the simple pharmacological action of this agent but to some immunopharmacological action.
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PMID:Promotion of spontaneous diabetes in non-obese diabetes-prone mice by cyclophosphamide. 653 55

Pancreatic islets from BALB/c (H-2d) mice are rejected within 14 days of transplantation to the kidney capsule of allogeneic, CBA/H (H-2k) recipients. Cyclophosphamide pretreatment of the islet donor reduced the intensity of the allograft response, and these islets undergo a more chronic rejection process. Islets from cyclophosphamide-pretreated donors can be cultured in a gas phase of 95% O2 and 5% CO2, provided the islets are aggregated into clusters of about 50 islets. After a culture period of 7--12 days, the islet tissue was transplanted to normal allogeneic recipients, where the tissue elicited little or no allograft response over a 3-mo observation period.
Diabetes 1980
PMID:Successful allotransplantation of mouse pancreatic islets to nonimmunosuppressed recipients. 676 18

In patients with maturity onset diabetes serum chlorpropamide concentrations (s-CPA) and fasting blood glucose (FBG) were measured before and after self recording of drug intake in order to evaluate the role of compliance with the therapeutic regimen in variation in s-CPA and clinical outcome. Nine out of 57 patients (16%) had to be excluded because they did not comply with the clinical routines and the test procedure. Of the remaining 48 patients, only two recorded small deviations from the prescribed dosage, and nine (19%) noted variations in medication time of more than +/- 2h. By contrast, irregular drug intake was indicated in 29 of the 48 patients (60%) based on statistical evaluation of changes in s-CPA. Clinical control (FBG) was influenced significantly in only half of these 29 patients. Improved adherence to the dietary regimen was observed in 12 of the 48 patients (25%). Patient medication behaviour seems to be an important determination of variation in s-CPA, and is as important as adherence to the dietary regimen in clinical control of "drug requiring" patients with maturity onset diabetes.
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PMID:Irregular drug intake and serum chlorpropaminde concentrations. 742 97

Serum chlorpropamide concentrations (s-CPA) were determined and related to clinical findings in 83 outpatients with maturity onset diabetes. The daily doses of CPA (mg/kg) varied six-fold, but s-CPA ranged 18-fold between the patients. There was a significant correlation between dose and s-CPA (r = 0.61), which rose to 0.75 in the 30 patients who had prescribed no other drugs. Patients given other drugs concomitantly were over-represented amongst subjects with extreme values of apparent plasma clearance of CPA. There was no correlation either between serum creatinine or age and s-CPA. Of the 83 patients 40 (48%) had acceptable blood and urinary glucose values according to our criteria; but as 17 were overweight, only 23 patients (28%) had acceptable clinical control. Of the remaining 60 patients, too low a dose was being given to only 12, and dietary failure was the most probable explanation in the others. Thirteen patients (16%) probably did not need CPA. It is likely that this is a partial explanation for the high utilisation of oral antidiabetic drugs in Sweden. There was no general correlation between dose or s-CPA and blood glucose values, but analysis of s-CPA may still be of value in explaining unexpected changes in clinical control.
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PMID:Wide variation in serum chlorpropamide concentration in outpatients. 742 98

To elucidate the roles of macrophages in the pathogenesis of NOD murine diabetes, peritoneal macrophages from NOD mice were injected into young NOD mice. We used 12 to 20 week-old NOD mice of both sexes as donors, and sex-matched 2-week-old NOD mice as recipients. Cyclophosphamide (CY), 200 mg/kg, was intraperitoneally injected into the donors. Two weeks later, peritoneal exudate cells (PEC) were collected from the diabetic donors. Macrophage-rich fractions (MRF) were collected by adherence. Then PEC(5-8 x 10(6)) or MRF(3-7 x 10(6)) were transferred, intraperitoneally, to the recipients. Two weeks later, some of the recipients were killed in order to perform immunofluorescent analysis of splenocytes and to assess pancreatic histology. Mac 1 positive splenocytes were increased in PEC- and in MRF-injected recipient mice. Insulitis was seen in PEC- and MRF-injected mice, but not in controls. Some of the recipients were injected with CY, 200 mg/kg, intraperitoneally, at two weeks post cell transfer. Two weeks after CY injection, the animals were examined for the presence of diabetes. The incidences of diabetes were 67% in PEC-injected mice, 40% in the MRF-injected group, and 3% in the controls. These results suggest that peritoneal macrophages accelerate the disease process in NOD mice.
Diabetes Res Clin Pract 1994 Jun
PMID:Acceleration of diabetes in young NOD mice with peritoneal macrophages. 795 11

Based on previous studies showing that allogeneic islets transplanted into the thymus can induce donor-specific unresponsiveness, we investigated in the nonobese diabetic (NOD) mouse the effect of intrathymic islet isografts on preventing autoimmunity directed against pancreatic islet antigens. Islets prepared from newborn NOD pancreata were injected into one lobe of the thymus of 10- to 11-day-old female NOD mice (experimental group) with no immunosuppression. PBS alone was used for injection into age- and sex-matched litter mates (control group). Thirty of 32 (94%) experimental mice remained normoglycemic for over 30 weeks. Well-formed islets with no indication of insulitis were found in the thymus of these 30 mice, whereas no grafted islets were found in the 2 mice that became diabetic at 17 and 19 weeks, respectively (technical failures). In the control group, 10 of 32 (31%) mice became diabetic between 20 and 29 weeks. This diabetic incidence was, however, lower than that in our colony female mice. In the pancreas of experimental mice, 90.9% of islets were free of infiltrates, whereas only 13.1% of islets were intact in control mice. The spleens of 30-week-old experimental mice contained a slightly higher percentage of CD8+ T cells (P < 0.05) than those of control mice. Cyclophosphamide injections at 30 weeks induced diabetes in 4 of 9 experimental mice. The 2 lines of evidence, (1) marked reduction in insulitis of intrathymic islet-grafted mice and (2) induction of diabetes after treatment with cyclophosphamide, suggest that both thymic clonal deletion and peripheral tolerance may play a role in preventing diabetes.
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PMID:Prevention of overt diabetes and insulitis by intrathymic injection of syngeneic islets in newborn nonobese diabetic (NOD) mice. 821 62

Four pancreatic islet-specific CD4+ helper T (Th) 1 (Th1) clones and two Th1 clones transduced with an SRalpha promoter-linked murine IL-10 (mIL-10) cDNA of 2.0-6.0 x 10(6) cells were adoptively transferred to nonobese diabetic (NOD) mice at age 8 d. Cyclophosphamide (CY) was administered at age 37 d (plus CY), and the incidence of diabetes and the histological grade of insulitis were examined at age 47 d. After the adoptive transfer of IL-10-transduced Th1 cells, polymerase chain reaction (PCR) and reverse-transcription (RT)-PCR detected the neo gene and the retrovirus vector-mediated IL-10 mRNA in situ in recipient islets, respectively. RT-PCR detected the decrease of IFN-gamma mRNA relative to IL-10 mRNA in IL-10-transduced Th1 clones in vitro and also in recipient islets. All four wild type Th1 clones plus CY induced the insulitis grade of 2.75 and diabetes in 66% of recipient NOD mice. IL-10-transduced two Th1 clones plus CY induced periinsulitis with the grade of 1.43 and diabetes in 8.0%. The 1:1 mixture of wild type Th1 cells and IL-10-transduced Th1 cells plus CY induced periinsulitis with the grade of 1.85 and diabetes in 20%. The suppression of diabetes through decreasing IFN-gamma mRNA by the tissue-specific delivery of IL-10 to pancreatic islets with IL-10-transduced Th1 cells affords us the starting basis to develop the gene therapy for autoimmune diabetes.
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PMID:Prevention of adoptively transferred diabetes in nonobese diabetic mice with IL-10-transduced islet-specific Th1 lymphocytes. A gene therapy model for autoimmune diabetes. 887 37

The therapeutic effect of most immunosuppressive agents is unspecific and therefore often limited by an increased risk of infection by viral, bacterial or fungal organisms as well as by an increased incidence of malignant neoplasms. This short review includes the most commonly used immunosuppressants such as corticosteroids, azathioprine, methotrexate, cyclophosphamide and cyclosporine. The most common risks of long-term corticosteroid treatment are Cushing-like changes, decreased glucose tolerance and the usually benign steroid diabetes. Also clinically important is osteoporosis, since it can be prevented by physical training, calcium supplementation and treatment with vitamin D if necessary. Although there is still no proof of a significantly increased risk of peptic ulcer during steroid therapy, patients may develop gastrointestinal hemorrhage and even perforation without producing pain while being treated with corticosteroids. Mineralocorticoid effects, such as salt and water retention, are seen only with hydrocortisone and prednisone, whereas with synthetic steroids such as dexamethasone, sodium retention is absent despite their strong antiphlogistic activity. The most important side effect of the cytotoxic agents azathioprine, methotrexate and cyclophosphamide is marrow suppression. Due to the high turnover of neutrophils, patients most frequently suffer neutropenia rather than thrombocytopenia or anemia. Neutropenia, as well as impaired humoral and cellular immune mechanisms, are responsible for increased susceptibility to bacterial, viral or parasitic diseases during immunosuppressive therapy. Hepatotoxicity has been reported among patients receiving azathioprine (cholestatic hepatitis) and methotrexate (elevated AST levels and, rarely, liver fibrosis or cirrhosis). Cyclophosphamide causes hemorrhagic cystitis in a substantial proportion of patients, as well as an increased incidence of urothelial neoplasms. Both these side effects may be prevented by Mesna. The most important side effects of cyclosporine are acute and chronic nephrotoxicity usually associated with significantly elevated plasma levels of the drug. It must be borne in mind that severe nephrotoxicity may occur in patients receiving cyclosporine and ketoconazole together, since the latter may inappropriately increase the plasma cyclosporine level.
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PMID:[Immunosuppression--a tightrope walk between iatrogenic harm and therapy]. 892 65


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